Hepatology Clinical

Abstract

10

Liver outcome score predicts long term clinical outcomes in primary biliary cholangitis: a multi-centre study

Dujinthan Jayabalan^1,2, Leon A Adams^1,2, Yi Huang¹, Luis Calzadilla Bertot^1,2, Wendy Cheng³, Simon Hazeldine⁴, Briohny Smith¹, Gerry MacQuillan^1,2, Michael Wallace^1,2, George Garas^1,2 and Gary P Jeffrey^1,2

¹Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, Australia; ²Medical School, University of Western Australia, Nedlands, Australia; ³Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Australia; ⁴Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Perth, Australia

Background and Aim: Few predictive models of survival exist for primary biliary cholangitis (PBC) patients. This study investigated the natural history and assessed the accuracy of models for predicting liver-related outcomes in PBC patients.

Methods: PBC patients were identified from the state-wide Hepascore and Clinical Outcome (HACO) cohort. Patients with PBC overlap syndromes were excluded. Overall death or transplant, liver-related mortality (liver-related death or transplant), and liver-related decompensation were determined using a population-based data linkage system. Accuracy of baseline Liver Outcome Score (LOS), composed of albumin, GGT, hyaluronic acid, age, sex, Hepascore and MELD were examined for predicting clinical outcomes.

Results: 157 PBC patients (13% male, median age 60.5 years, median MELD 6, median Hepascore 0.22, 34% cirrhotic at enrolment) were followed for a median of 4.0 years (range, 0.01-9.5 years). Twelve patients died, 8 had liver-related deaths and 3 underwent liver transplant. Ten patients decompensated and two developed hepatocellular carcinoma. 5-year transplant-free survival was 92% (95% CI: 85-96%) overall, 71% (95% CI: 48-86%) in cirrhosis and 97% (95% CI: 91-99%) in non-cirrhotics (p<0.0001). 5-year liver-related mortality free rate was 95% (95% CI: 89-98%) in all, 76% (95% CI: 53-89%) in cirrhosis and 100% (95% CI: 100-100%) in non-cirrhotics (p<0.0001). Median time-to-decompensation was 3.3 years (range, 0.2-8.6). 5-year liver-related decompensation-free rate was 89% (95% CI: 78-95%) in all, 53% (95% CI: 22-76%) in cirrhosis, 98% (95% CI: 89-99.8%) in non-cirrhotics (p<0.0001). Multivariate analysis found LOS predicts overall death or transplant in all patients (HR 2.14; (95% CI: 1.26-3.62), p=0.005, C-statistic 0.89) and in cirrhotics (HR 2.24; (95% CI: 1.11-4.50), p=0.024, C-statistic 0.85). LOS predicted liver-related mortality in all (HR 2.40; (95% CI: 1.11-5.19), p=0.027, C-statistic 0.93) and in cirrhosis (HR 2.06; (95% CI: 0.98-4.31), p=0.056, C-statistic 0.93). LOS predicted liver-related decompensation in all (HR 1.85; (95% CI: 1.24-2.76), p=0.003, C-statistic 0.92) and in cirrhosis (HR 1.58; (95% CI: 1.12-2.22), p=0.032, C-statistic 0.83). MELD predicted overall death or transplant (HR 1.67; (95% CI: 1.14-2.44), p = 0.008) and liver-related mortality (HR 1.87; (95% CI: 1.10-3.18), p = 0.020) in all. There were no predictors of liver-related outcomes in non-cirrhotics.

14

Artemisinin-induced cholestatic liver injury and intrahepatic ductopenia

Joel Thio

The Prince Charles Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia

Introduction: Artemisinin, an ancient Chinese herbal remedy known colloquially as “Qinghao”, is now used as treatment for malaria as recommended by the World Health Organisation. There have been few reports of artemisinin-induced liver injury. Most of these instances of hepatotoxicity are reportedly due to prolonged use of herbal remedies containing artemisinin. To our knowledge, we report the first case of intrahepatic ductopenia in a patient with cholestatic liver injury after artemisinin use.

Case report: A 56-year-old male presented with a one-week history of abdominal pain and three days of jaundice, pruritis, and dark urine. His medical history only included hyperlipidemia and a previous laparoscopic appendicectomy 16 years ago. He had no prior history of liver disease, denied alcohol consumption and recreational drug use, and had no risk factors for viral hepatitis. He denied any regular medications. The patient had taken artemisinin for a total of thirty days, beginning five weeks prior to presentation at a dose of 392mg twice daily. He ceased it one week prior to presentation, at the onset of his abdominal pain. His initial pattern of hepatic injury was mixed with an R value of 2.85. Liver core biopsy revealed predominantly portal inflammation with bile duct epithelial injury (Figure 1) and ductopenia (6 bile ducts identified out of 18 portal tracts), as well as prominent centrilobular acute cholestasis. He scored five points using the Roussel Uclaf Causality Assessment Method.

Conclusion: In summary, we report a severe case of possible artemisinin-induced cholestatic liver injury with severe intrahepatic ductopenia. Given the rare but increasing number of case reports of liver injury associated with artemisinin, we suggest further efforts to control the use of these medicinal compounds.

19

Health-related quality of life outcomes in hepatocellular carcinoma patients undergoing systemic therapies: a systematic review

Dujinthan Jayabalan^1,2, Sugam Dhakal^1,2, Aarohanan Raguragavan², Akshat Saxena³, Gary P Jeffrey^1,2, Luis Calzadilla Bertot^1,2, Leon A Adams^1,2 and Michael Wallace^1,2

¹Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, Australia; ²Medical School, University of Western Australia, Nedlands, Australia; ³Department of Cardiothoracic Surgery, Fiona Stanley Hospital, Perth, Australia

Background and Aim: Systemic therapies (immune checkpoint inhibitors, tyrosine kinase inhibitors and monoclonal antibodies) are considered first-line therapy for advanced hepatocellular carcinoma (HCC). The poor outcomes experienced by patients with advanced HCC coupled with potential significant treatment side-effects underpins a strong rationale to measure the impact of systemic therapies on health-related quality of life (HRQOL). The objective of this systematic review is to quantify the effect of systemic therapies on HRQOL outcomes in HCC patients when compared to a pre-treatment state, other systemic therapies and to transarterial radioembolisation (TARE).

Methods: Using predetermined eligibility criteria, a literature search using Pubmed and EMBASE between January 2008 and March 2024 was conducted by two independent reviewers for randomised controlled trials, observational studies and case-series. Google Scholar, MEDLINE and included study bibliographies were also manually searched. Narrative review was used to synthesise results. The review was structured according to PRISMA guidelines and was prospectively registered in the PROSPERO register (CRD42024521699).

Results: Twenty-nine studies with 10472 patients from fourteen countries (location, n: Europe, 15; Asia, 10; USA, 3; Brazil, 1) using eight different HRQOL instruments were included (instrument, n): QLQ-C30, 16; QLQ-HCC18, 9; EQ 5D, 8; FACT-Hep, 5; FACT-G, 2; FACT-HS, 1; FHSI-8, 5; SF-36, 1. Eighteen (62%) studies assessed sorafenib and four (14%) studies assessed atezolizumab-bevacizumab (atezo-bev). Of the remaining studies, five (17%) studies investigated PD-1 inhibitors (three pembrolizumab, two nivolumab), two (7%) studied lenvatinib, two (7%) studied ramucirumab, and one study each evaluated cabozantinib, dovitinib, brivanib, regorafenib and durvalumab-tremelimumab. Compared to baseline, patients on atezo-bev and sorafenib both experienced a significant reduction in HRQOL. Lenvatinib nominally decreased HRQOL, whereas HRQOL did not change in patients on PD-1 inhibitors. Atezo-bev and lenvatinib both significantly delayed HRQOL deterioration compared to sorafenib, and in combination with lenvatinib, pembrolizumab significantly improved HRQOL compared to lenvatinib alone. Patients on nivolumab had nominally superior HRQOL when compared to patients on sorafenib. Compared to TARE, atezo-bev delayed time to deterioration in HRQOL, whereas sorafenib had significantly worse HRQOL.

Conclusion: Despite worsening HRQOL outcomes compared to baseline, the first-line agents atezo-bev and lenvatinib improved HRQOL in comparison to sorafenib. Patients on PD-1 inhibitors or nivolumab experienced no change in HRQOL. Sorafenib significantly worsened HRQOL compared to TARE. As majority of the included studies assessed sorafenib, which has been superseded by newer systemic therapies, further trials evaluating HRQOL in newer agents is required.

23

The prevalence of intestinal failure-associated liver disease in patients on long-term home parenteral nutrition

Nicholas Wan^1,2,4, Sharifah Syed Mustaffah^3,4, Andrew Holt^3,4, Kate Muller^2,4, Jeyamani Ramachandran^2,4, Shailesh Bihari^3,4, Steven Galluccio^3,4, Richard Woodman⁴, Sumudu Narayana², Rachel Wundke², Rosalie Altus², Qun Chen³, Maria Kielpikowska³ and Alan Wigg^2,4

¹Gastroenterology Department, Lyell McEwin Hospital, Australia; ²Hepatology & Liver Transplant Medicine Department, Southern Adelaide Local Health Network, Bedford Park, Australia; ³Intensive Care Unit, Flinders Medical Centre, Bedford Park, Australia; ⁴College of Medicine and Public Health, Flinders University, Bedford Park, Australia

Background and Aim: Intestinal failure-associated liver disease (IFALD) is a recognized complication of long-term parenteral nutrition (PN). Estimates for prevalence range widely from 25-100%, due to differences in patient populations and parenteral nutrition regimens. This study aims were to estimate IFALD prevalence in adults receiving long-term home-PN (HPN), describe the biochemical and elastography characteristics of IFALD, and identify predictors of IFALD.

Methods: This was a single-centre, retrospective cohort study. Patients were included if currently on long-term (>12 weeks) HPN or had received long-term HPN in the last 10 years. Patients with any malignancy or pre-existing liver disease were excluded. There is no consensus on the criteria for IFALD diagnosis. Early detection is crucial due to the rapid progression of disease. We defined IFALD as any persistent, unexplained, elevation (>1.5x ULN) of LFTs for >3 months over Cavicchi's criteria of >6 months. Vibration controlled transient elastography (VCTE), including controlled attenuation parameter score, was performed in all patients. The covariates for univariate and multivariate logistic regressions were: age, gender, HPN calories-per-week, HPN frequency, HPN-duration, HPN-formula, current or past-HPN, indication for HPN, BMI, lipids pre and 3-months-post HPN commencement.

Results: 24 patients on long-term HPN were included. The most common indications for HPN were surgery (45.8%) and Crohn’s Disease (29.2%). The median (IQR) duration of HPN and calories-per-week was 42.5 (15.8-62.3) months and 6647kcal (3476.3-8471.3) respectively. IFALD was present in 15 (62.5%) patients. 9/15 (60%) had short-gut syndrome. In IFALD patients, the most common pattern of abnormality was cholestasis, with 12 (80%) patients demonstrating a cholestatic pattern. In IFALD patients, the median (IQR) values for GGT, ALP, ALT, AST, and Bilirubin were 254U/L (132-312), 233U/L (188.5-365), 54U/L (30.5-113.5), 44U/L (31.5-68.5), and 7umol/L (5.5-16) respectively. VCTE revealed likely significant fibrosis (fibrosis score ≥2) in 3 (20.0%) patients and likely significant steatosis (steatosis score ≥2) in 2 (13.3%) patients. 12 (80%) patients on current-HPN had IFALD, versus 3/9 (33.3%) past-HPN patients. On univariate analysis, the only significant association was current versus past-HPN (OR = 8.0, 95%CI= 1.2-52.2, p-value=0.03). There were no significant associations with IFALD on subsequent multivariate analysis.

27

The Portal Decompensation Score – a validated predictive model of portal hypertension related liver decompensation events in cirrhosis

Angus W Jeffrey^1,2, Avik Majumdar^3,4, Luis Calzadilla Bertot¹, Michael Wallace^1,2, Gary P Jeffrey^1,2, Ivy Huang¹, John Joseph⁵, George Garas¹ and Leon A Adams^1,2

¹Sir Charles Gairdner Hospital, Perth, Australia; ²The University of Western Australia, Perth, Australia; ³The Austin Hospital, Melbourne, Australia; ⁴The University of Melbourne, Melbourne, Australia; ⁵Pathwest, Perth, Australia

Background and Aim: Accurate assessment of portal hypertension is crucial in management and risk assessment. The Baveno VII guidelines identified a need for accurate non-invasive risk stratification of portal hypertension. The aim of this study was to develop a novel score that accurately predicts portal hypertension related decompensation (variceal haemorrhage, ascites, hepatic encephalopathy).

Methods: Adults with cirrhosis in Western Australia from 2004 to 2015 were followed until occurrence of a decompensating event. Cirrhosis was defined by baseline Hepascore values using validated cut-points; ≥0.95 for alcoholic liver disease, ≥0.96 for non-alcoholic fatty liver disease, ≥0.84 for all other causes. The cohort was split into a training and validation dataset at a 70:30 ratio. Associations between serum markers and decompensation was assessed by competing risk analysis, and model accuracy compared using time dependent area under the curve (tAUC).

Results: A total of 1384 participants with cirrhosis were included in the final analysis (967 in the training cohort, 417 in the validation cohort). 698 (72%) and 302 (72%) participants were male in the training and validation cohorts respectively. The median age was 54 years in both groups. There were 172 (17.8%) and 64 (15.3%) episodes of decompensation in the training and validation cohorts (p=0.60) after an average (standard deviation) follow-up period of 3.59 (± 2.32) and 3.76 (± 2.38) years respectively. The average MELD score at inclusion was 9.4 (± 4.3) and 9.6 (± 4.4) respectively (p=0.43). 85% in the training cohort and 96% in the validation cohort were Child Pugh A, with the remainder being Child Pugh B. Competing risk analysis found bilirubin, alanine transaminase (ALT), alkaline phosphatase (ALP), albumin and platelets to be independent predictors of decompensation and these were combined into a final model - the Portal Decompensation Score (PDS). The model produced a calibration slope of 0.99 (training) and 1.00 (validation). Overall model performance was good with an integrated Brier score of 0.14 (training) and 0.17 (validation). A cut-off value of -3.102 was selected using the Li and Youden criteria, with a cumulative incidence of 6.5% vs 28.5% at 2-years and 10.8% vs. 43.8% at 5-years (sub–Hazard Ratio 5.0, p<0.001). The predictive accuracy of the model in the entire cohort was very good with tAUC of 0.81 at 2-years and 0.79 at 5-years. When assessed for aetiology of liver disease the tAUC at 2-years was excellent in predicting decompensation in Hepatitis C (0.83), Hepatitis B (0.87) and autoimmune hepatitis (0.81), good for NAFLD (0.71) and not useful for alcohol related cirrhosis (0.59).

Conclusion: The Portal Decompensation Score (PDS) uses simple, readily available serum markers to accurately identify those patients with liver cirrhosis who are at higher risk of having a portal hypertension related decompensating event. This new model may provide benefit in assessment of patients regarding ongoing surveillance requirements, including those who may benefit from surveillance endoscopy, primary prevention of varices with non-selective beta blockade or even primary prophylaxis for hepatic encephalopathy.

32

Uncommon presentation of a rare congenital portosystemic shunt (Abernethy malformation) in adulthood with infective endocarditis and synthetic dysfunction

Osamah Al-obaidi¹, Alice Lee¹, Ken Liu², Emily He¹ and Karen Waller¹

¹Concord Repatriation General Hospital, Sydney, Australia; ²Royal Prince Alfred Hospital, Sydney, Australia

Introduction: Abernethy malformation is a congenital vascular anomaly of extrahepatic portosystemic shunting, where the splanchnic circulation bypasses the liver and directly joins inferior vena cava (IVC). While most patients present in childhood, adults can present with jaundice, hepatic encephalopathy, variceal bleeding, and/or pulmonary arterial hypertension (PaHT). Definitive management involves shunt closure, or liver transplantation. We report an uncommon presentation of this rare condition.

Case report: A 41-year-old man presented to the emergency department with fever, lethargy, jaundice and atraumatic left wrist pain. He had no underlying liver disease, minimal alcohol consumption and was not overweight. Physical examination revealed tachycardia, fever, and hypotension. He was alert, fully orientated with no asterixis. He was jaundiced, had non-blanching petechiae and left wrist tenderness with reduced range of movement. There was massive splenomegaly, normal liver span and lower limb pitting oedema. Auscultation revealed a pansystolic murmur over the tricuspid area. Blood tests showed severe thrombocytopenia (25x10x9/L), conjugated hyperbilirubinaemia (179 umol/L) and hypoalbuminaemia (20 g/L), but normal alanine transaminase (32 U/L) and aspartate transaminase (40 U/L). He had prolonged PT (25.3 seconds), APTT (41 seconds) and INR (2.2). CT scan demonstrated massive splenomegaly, distended superior mesenteric and splenic veins with multiple varices communicating with a distended IVC, in keeping with Abernathy malformation (Figure 1). Portal vein was absent with no evidence of cavernous transformation. Liver US confirmed the absence of the portal vein. Liver surface was smooth, with moderately elevated elastography (Fibroscan 10.8kPa). Further investigations excluded viral, hereditary, and autoimmune aetiologies of liver disease. Transthoracic echocardiogram suggested and right sided heart catheterisation confirmed severe PaHT, with pulmonary artery pressure of 51 mmHg.

He was admitted under the care of cardiology team and treated with empirical antibiotics for infective endocarditis, directed when Staphylococcus aureus was confirmed in blood cultures. Later, transoesophageal echocardiogram excluded cardiac vegetations. Left wrist washout culture confirmed Staphylococcus aureus, indicating 4 weeks of intravenous Flucloxacillin. He was discharged from hospital after 1 month of acute care. He was commenced on Macitentan and Sildenafil, which improved pulmonary artery pressure to 28 mmHg. Based on persisting MELD score of 18 and portopulmonary hypertension, he has been listed for liver transplant.

Conclusion: This unusual presentation of Abernethy malformation with sepsis and synthetic dysfunction highlights a rare cause of portal hypertension. While the directed treatment of complications are familiar to clinicians, liver transplantation remains the definitive treatment.

38

Improving assessment of suspected non-alcoholic fatty liver disease in type 2 diabetics in primary care: a quality improvement project

Matthew Bartlett¹, Helen McClelland² and Erin Heald³

¹Sir Charles Gairdner Hospital, Perth, Australia; ²Gosforth Memorial Medical Centre, Newcastle Upon Tyne, United Kingdom; ³Newcastle University, Newcastle Upon Tyne, United Kingdom

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is an increasingly common cause for cirrhosis with a spectrum of disease from steatosis to fibrosis and cirrhosis. NAFLD is highly associated with type 2 diabetes (T2DM), present in 60% of patients with T2DM. Surveillance of NAFLD to identify those at risk of progression to cirrhosis can enable interventions reducing progression. The aim of this project was to explore management of patients with T2DM and abnormal LFTs at one general practice (GP) surgery and improve assessment of NAFLD for patients in this high-risk population.

Methods: An initial evaluation of practises was carried out. Patients with T2DM and elevated serum alanine aminotransaminase (ALT) during 2022 were identified through searching electronic records. Records were reviewed and evaluated for: baseline characteristics, existing diagnosis of NAFLD, ultrasound scan (USS) evaluation of liver, calculation of fibrosis- 4 (FIB-4), and referral to secondary hepatology service. Following this audit, two changes to practise were made. An invite for further assessment was offered to allow repeat blood tests and FIB-4 calculation, and education on NAFLD and modifiable lifestyle factors. The second change was to include aspartate aminotransferase (AST) measurement in the routine annual T2DM reviews to calculate the FIB-4 score in all patients. A repeat evaluation of practises was completed after changes were implemented.

Results: In the initial evaluation 39 patients with T2DM were found to have had an elevated ALT. Of these 4 were already diagnosed with NAFLD. 5 had other causes for deranged ALT. 2 had been investigated with USS, 0 had a fibrosis risk score documented. On recall, 14 patients attended for a screening and education appointment. Of these 4 were found to have elevated FIB-4 score and were referred to hepatology services, 6 patients were found to have fatty changes on a prior liver USS, 3 patients were found to have new fatty changes on USS. In the re-evaluation of practises, at routine T2DM reviews in the first quarter of 2023, 12 patients with T2DM had a deranged ALT. Of these patients a FIB-4 score was calculated in 12 patients with an elevated fib-4 score in 1 patient and were referred to hepatology services.

Conclusion: This project demonstrated the under investigation of suspected NAFLD in T2DM in general practise. Changes to routine bloods and default calculation of fibrosis screening tests at diabetic improved the diagnosis and appropriate referral of patients with NAFLD in this high-risk population.

44

Hepatosplenic candidiasis in a non-neutropaenic patient post endoscopic cholangiopancreatography

Carl Cosgrave¹, Eliza Flanagan^1,3, Jack Shembrey¹ and Jonathan Watson^1,2

¹Barwon Health, Geelong, Australia; ²Deakin University, Geelong, Australia; ³Monash University, Melbourne, Australia

Introduction: Disseminated hepatosplenic candidiasis (HSC) is a fungal infection of the liver and spleen. It typically occurs in patients with haematologic malignancy and prolonged neutropenia. Candida species and Nakasoemyces glabrata are known to colonise the gastrointestinal tract, and less commonly the biliary system, especially in hospitalised patients^1,2. Whilst, the pathogenesis of hepatosplenic candidiasis is poorly understood, it is proposed that breakdown of mucosal integrity within the gut leads to opportunistic invasion through the portal system and significantly higher hepatosplenic involvement than other organs³. HSC typically manifests as persistent fungaemia and large liver lesions on imaging that may regress during periods of neutropaenia due to a reduction in immune activity^,4. In immunocompetent, non-neutropaenic and noncritically-ill-patients, post-ERCP candidemia is extremely rare. However, Candida and other fungal species have been increasingly implicated in cases of cholangitis¹ and HSC in non-neutropaenic patients following ERCP⁵. Other risk factors including pancreatitis, intravenous access, prolonged antibiotic therapy and mucosal barrier disruption have also been identified⁵. In this case, the history of HHT may have played a role by affecting the phagocytic activity of macrophages and neutrophils and reducing the production of pro-inflammatory cytokines; both of which can increase susceptibility to opportunistic infections⁶.

Case report: A 53-year-old female was admitted to hospital with worsening cholestatic liver function test derangement and right upper quadrant abdominal pain. Her past medical history includes hereditary haemorrhagic telangiectasia (HHT), treated with Bevacizumab, a partial hepatectomy with cholecystectomy for arteriovenous malformations, atrial fibrillation (not anticoagulated) and type 2 diabetes mellitus. An MRCP showed a dilated common bile duct (CBD) (10mm) and an endoscopic ultrasound was performed, suggesting a distal filling defect in the CBD. An ERCP with sphincterotomy extracted 3 small stones. The procedure was complicated by acute pancreatitis, and subsequent Enterobacter Cloacae bacteraemia and Nakaseomyces Glabrata fungaemia on day 12 post-operatively. Intravenous meropenem and caspofungin was commenced, however the infection progressed to disseminated fungaemia (demonstrated on imaging; see image 1) with refractory culture positivity on days 12-15 and 31-43. Antifungal treatment was broadened with liposomal amphotericin B and cultures cleared on day 44 post-op. Serial abdominal computed tomography (image 2, 3) demonstrated progressive enlargement of hepatic lesions consistent with abscesses, as well as splenic infarcts secondary to fungal infection. Biopsy was not performed due to the risk of severe bleeding from known liver arteriovenous malformations. The patient was not neutropenic at any stage. She continued to deteriorate and passed away on day 81 of admission (day 66 post op).

References

1. Lenz, P, Conrad, B, Kucharzik, T, Hilker, E, Fegeler, W, Ullerich, H et al. Prevalence, associations, and trends of biliary-tract candidiasis: a prospective observational study. Gastrointest Endosc. 2009 Sep; 70(3): 480-7.

2. Lenz, P, Eckelskemper, F, Erichsen, T, Lankisch, T, Dechêne, A, Lubritz, G, et al.. Prospective observational multicenter study to define a diagnostic algorithm for biliary candidiasis. World J Gastroenterol. 2014 Sep 14; 20(34): 12260-8.

3. Kontoyiannis, D, Luna, M, Samuels, B, Bodey, G. Hepatosplenic candidiasis. A manifestation of chronic disseminated candidiasis. Infect Dis Clin North Am. 2000 Sep; 14(3): 721-39.

4. Pestalozzi, B, Krestin, G, Schanz, U, Jacky, E, Gmür, J, Hepatic lesions of chronic disseminated candidiasis may become invisible during neutropenia. Blood. 1997; 90(10): 3858.

5. Park, T, Yang, Y, Shin, S, Bang, C, Suk, K, Baik, G, et al. Candidemia after endoscopic retrograde cholangiopancreatography in an immunocompetent patient: A case report and literature review. Saudi J Gastroenterol 2018; 24: 135-7.

6. Rodríguez-García, J, Zarrabeitia-Puente, R, Fernández-Santos, R, García-Erce, JA. Infection prevention in patients with hereditary hemorrhagic telangiectasia. Haematologica. 2018 Oct; 103(10): e491-e492.

45

Home management of refractory ascites in decompensated cirrhosis with long-term abdominal drains: a pilot study

Jeyamani Ramachandran^1,2, Kylie Bragg¹, Jodie Altschwager³, Lindsay Moore³, Ramon Pathi⁴, Adam Koukourou⁴, Kate Muller^1,2 and Alan Wigg^1,2

¹Department of Gastroenterology and Hepatology, Flinders Medical Centre, Adelaide, Australia; ²Flinders University, Adelaide, Australia; ³Metropolitan Referral Unit, SA Health, Adelaide, Australia; ⁴Department of Radiology, Flinders Medical Centre, Adelaide, Australia

Background: Definitive therapies including liver transplantation and TIPSS are often not feasible in patients with decompensated cirrhosis (DC) and refractory ascites (RA). In such patients, RA is a palliative condition managed with frequent large-volume paracentesis (LVP) in hospital. This is associated with significant health and economic burden. Long term abdominal drains (LTAD) are a potential improved palliative care treatment alternative for RA in DC but have not been well studied. The aims of this pilot study were therefore to explore the feasibility, efficacy, safety and patient acceptability of LTAD use in patients with RA due to DC.

Methods: Prospective pilot study from September 2022 to September 2024 in a tertiary hepatology unit. Inclusion criteria were patients with RA and DC without TIPSS or LT options undergoing at least one LVP per month. Exclusion criteria were patients with loculated ascites, exophytic liver tumours, chronic abdominal pain, extensive abdominal wall scars, active spontaneous bacterial peritonitis (SBP) and without access to home-based nursing management of LTAD. Consenting participants were admitted for insertion of Rocket® LTAD catheters (Rocket Medical, Australia) in the angiography suite by interventional radiologists. Participants were managed by community nurses on discharge and underwent ascites drainage at home, two to three times per week. During each visit, one to two litres of ascites was drained as required. Antibiotic prophylaxis for SBP was provided throughout the duration of LTAD. Follow-up duration was for 6 months from insertion with the option of continuing LTAD afterwards.

Results: Feasibility: During the study period, 47 patients with RA due to DC were screened. 7 patients were referred for LT and 3 underwent LT. 5 patients underwent TIPSS. Nine patients were palliated or deceased. 13 patients did not meet the criteria for LTAD insertion and continue to be followed up. One patient could not undergo LTAD due to non-availability of community resources.12 patients consented for LTAD and two of them died before its insertion. One patient is awaiting insertion. Nine patients (3- alcohol related and 4 metabolic associated liver disease, one- non cirrhotic portal hypertension) underwent LTAD insertion. Participants were predominantly (56%) male with a median (IQR) age of 71(11) years. The median (IQR) duration of follow-up was 130(108) days.

Efficacy: Median number of LVPs before and after LTAD were 5 and 0 respectively. In LTAD participants, hospitalisation for LVPs did not occur except in one instance. In that participant, breakthrough hospital based LVPs were required in the context of a single episode of SBP.

Safety: Five patients died and none of the deaths were related to LTAD complications. Five participants experienced seven LTAD related adverse events. These included two episodes of SBP (one related to missed antibiotic prophylaxis and one related to blocked LTAD), one LTAD blockage (requiring removal and reinsertion) and a subsequent accidental dislodgement leading to study withdrawal, one leakage around LTAD (managed with increased frequency of LTAD), one cellulitis at LTAD site (managed with oral antibiotics) and one LTAD removal and study withdrawal due to pain (within one week of insertion).

Acceptability: The majority (8/9) of participants preferred LTAD to LVPs and reported high levels of satisfaction with LTAD. Three out of four participants who completed 6 months of study opted for continuation of LTAD. The fourth participant had LTAD removed due to recompensation of DC.

Conclusions: For participants in this study with RA and a lack of definitive treatment options for DC, LTAD was a feasible, safe, effective, and acceptable alternative to LVPs. Its potential to replace LVPs, improve quality of life and reduce healthcare costs in DC needs to be investigated in large multicentre studies before further recommendations can be made.

53

A cross sectional study of the prevalence of chronic liver disease risk factors and liver fibrosis in a remotely living Indigenous Australian population

Alan Wigg^1,2, Sumudu Narayana¹, Richard Woodman², Michael Nugent³, Arlene Ackland³, Damian Riessen³, Benjamin Wigg⁴, Kate Muller^1,2 and Jeyamani Ramachandran^1,2

¹Southern Adelaide Local Health Service, Adelaide, Australia; ²Flinders University of South Australia, Adelaide, Australia; ³Umoona Tjutagku Health Service, Coober Pedy, Australia; ⁴Bond University, Robina, Australia

Background and Aim: Remotely living Indigenous Australians have disproportionate mortality from cirrhosis and hepatocellular cancer. However, there are no local population studies examining the prevalence of chronic liver disease (CLD) in remote communities. The main aims of this study were therefore to study a remote Indigenous population to determine the prevalence of CLD risk factors and the prevalence of significant fibrosis as defined by a FIB-4 score of ≥ 2.67.

Methods: The study design was a retrospective analysis of an electronic medical record database of a remote Aboriginal community-controlled health service. The setting was an Aboriginal controlled community health service located in a remote South Australian town with a 15% Indigenous Australian population. Participants were all adult Indigenous Australians between the ages of 35 and 65 years. Age and gender adjusted linear regression analysis was used to examine risk factors associated with elevated FIB-4 score.

Results: 83.9% of the study population had at least one CLD risk factor and 45% of the population had multiple CLD risk factors. The most prevalent risk factors were alcohol misuse, diabetes and obesity and are shown in Table 1. 3.7% and 11.8% of the population had a high risk (FIB-4 score ≥ 2.67) or intermediate risk (FIB-4 score ≥ 1.3) of significant fibrosis, respectively. On logistic regression analysis each additional CLD risk factor was associated with a 12.3% increase in FIB-4 mean (rate ratio increase=1.123, 95% CI=1.05-1.20, p=0.001). A history of alcohol misuse (RR=1.21, 95% C1 1.03-1.43, p=0.023) and history of hepatitis C (RR=1.56, 95% C1 1.10-2.24, p=0.016) was also associated with elevated FIB-4.

Conclusion: The study represents the first effort to describe global CLD risk factors and fibrosis assessment in a remote Indigenous Australian population. CLD risk factors and significant liver fibrosis were highly prevalent in this population. Multiple CLD risk factors frequently exist in Indigenous Australians and are associated with an additive risk of fibrosis. Integrating simple liver screening tests into adult health checks has the potential to detect CLD at an early and treatable stage, and to reduce the high morbidity and mortality from cirrhosis and hepatocellular cancer experienced by remotely living Indigenous Australians.

60

Liver Supportive Care: Improving multidisciplinary and palliative care in chronic liver disease

Kiran Gopinath Iyer, Jessica Howell, Tamsin Bryan, Yvonne Bonomo and Adam Pastor

St Vincent's Hospital Melbourne, Melbourne, Australia

Background and Aim: The introduction of palliative care for patients with chronic liver disease is frequently complicated by psychosocial barriers and substance use. In response, our institution established a Liver Supportive Care team with an open referral pathway to a multidisciplinary meeting involving gastroenterology, addiction medicine, and palliative care medicine. The patients discussed in these meetings have a diagnosis of significant chronic liver disease that is life-limiting; patients with complex psychosocial needs are prioritised. The multidisciplinary meeting occurs monthly, with the opportunity to discuss 3-4 patients in each session, including new patient referrals and current patient progress reviews. Individual patient care is coordinated by the liver clinical nurse consultants; enabling closer follow-up between specialist clinic appointments. In this study, we describe the cohort of patients, interventions offered and outcomes following review by the Liver Supportive Care team.

Methods: We performed a single-centre audit of patients discussed at palliative care multidisciplinary meetings between 11 November 2021 and 18 January 2024. Data points were obtained from a tertiary centre palliative care database and cross-referenced with medical records. The collected data included patient demographics, history of substance use, data on admissions, mortality, medical and psychiatric comorbidities and social context, specifically, accommodation. The primary outcome of this study was the audit of the patient cohort within out Liver Supportive Care model. Analysis of patient data was performed through descriptive statistics, with continuous variables presented as means or medians, and categorical variable presented as prevalence rates.

Results: Thirty patients were referred in the study timeframe; 24 had a severe alcohol use disorder and 5 patients had a polysubstance use disorder. 53% patients were male (N = 16) and the median age was 57 (IQR 45, 63), with ages ranging from 25 to 75 years. Cirrhosis was present in 93% of patients (N=28). The median number of discussions per patient was 2 (IQR 1, 2) with a range of 1 to 5. Prior to the initial Liver Supportive Care review, the median number of acute medical admissions was 8 (IQR 3, 11), with a range of 1 to 30. Following the initial multidisciplinary meeting, the median number of acute medical admissions was 1 (IQR 0, 4), with a range of 0 to 21. At time of data collection, 13 patients were deceased. Of the cohort, 8 patients died in acute inpatient units, 3 patients died in community settings, and 1 patient died in an inpatient palliative care unit. Meeting outcomes typically focussed on engaging with community palliative care, facilitating medical outpatient follow-up, encouraging engagement with addiction medicine services, formulation of harm minimisation strategies and initiating early discussions regarding end-of-life care.

Conclusions: The coordination of care amongst this cohort of patient with substance-related chronic liver disease remains an ongoing challenge for the healthcare system; affected by the unpredictability of their medical condition and the instability of their psychosocial environment. The patients of this cohort were typically younger than the community palliative care population, with a significant proportion suffering from severe AUD. Involvement of Liver Supportive Care was associated with a dramatic reduction in acute medical admissions. Through early planning and implementation of community-based supports, we anticipate that this model of care may reduce crisis presentations, improve patient quality of life, and tailor end-of-life care to individual patient requirements.

61

Advanced liver disease affects a significant proportion of young people who inject drugs: analysis of the prospective SuperMIX cohort

Samantha Colledge-Frisby^2,4, Michael Curtis^2,4, Joan Ericka Flores^1,3, Jessica Howell^1,2,3 and Paul Dietze^2,4

¹St Vincent's Hospital Melbourne, Melbourne, Australia; ²Burnet Institute, Melbourne, Australia; ³University of Melbourne, Melbourne, Australia; ⁴Curtin University, Perth, Australia

Background and Aim: People who inject drugs are a key population for liver disease given the high risk of chronic viral hepatitis transmission. If left untreated, chronic viral hepatitis, alcohol-related (ALD), and metabolic-associated steatotic liver disease (MASLD) can lead to cirrhosis and liver function impairment. While we know that people who inject drugs are at risk of liver disease, the epidemiology and characteristics of liver outcomes in this group are not well-characterised.

Methods: We examined incidence, prevalence, and characteristics of liver disease hospitalisations among a prospective community cohort of people who inject drugs in Melbourne, Victoria (SuperMIX cohort). The cohort were linked to study serology, hospital admissions and mortality data from 2008-2019. We examined incidence and prevalence of liver disease by aetiology (chronic viral hepatitis, alcohol-related, MASLD) and disease progression (cirrhosis, decompensation, liver cancer).

Results: Of the 1287 participants in SuperMIX, 520 (40.4%) were hospitalised with a liver-related diagnosis. The most common aetiology for liver disease was hepatitis C virus (HCV; n=647, 50.3%), followed by hepatitis B virus (HBV; n=66, 5.1%), while MASLD (n<6) and ALD (n=13, 1.0%) were less common. Fifty-nine participants (4.6%) were diagnosed with liver cirrhosis, 57 (96.6%) of whom had decompensation. There were 68 hospitalisations due to liver decompensation, indicating incidence of 5.1 (95%CI=4.0-6.5) per 1000 person-years (PY). Incidence was relatively stable over the study period but peaked in 2018-2019 (Figure). There were an average 17.2 (SD=8) years between reported injecting initiation and first liver decompensation-related hospitalisation. Thirty percent of patients hospitalised with decompensation were 15–29 years old. Half of patients with liver decompensation had been hospitalised with an alcohol-related diagnosis over the study period.

Conclusion: Advanced liver disease affects a significant proportion of young people who inject drugs. Increasing access to effective strategies to manage comorbid alcohol use disorder may be particularly important for preventing advanced liver disease in this population.

62

Oesophageal varices screening and management in patients with chronic liver disease: A retrospective analysis of an Australian tertiary health service

Tsz Hong Yiu¹, Aisha Khalid^1,2, Hans Mautong^2,3, Jennifer Andraos¹, Emily Matejin¹, Kerrie Curin¹, Nicola McGuinn¹ and Zina Valaydon^1,4

¹Western Health, Melbourne, Australia; ²Department of Medicine, University of Melbourne, Melbourne, Australia; ³Department of Postgraduate Medical Education, Harvard Medical School, Boston, USA; ⁴Department of Medicine, John H. Stroger Jr Hospital of Cook County, Chicago, USA

Background and Aim: The Baveno Consensus Workshops recommend gastroscopy for advanced chronic liver disease (CLD) patients to detect varices, with Grade 2/3 varices advised to receive prophylactic treatment using non-selective beta blockers (NSBB) or band ligation. This study assesses adherence to these criteria among CLD patients at Western Health (WH), a tertiary health service serving a population of 1.2 million in socioeconomically disadvantaged Melbourne suburbs with a high density of non-English speaking background (NESB) immigrants and low health literacy. This demographic presents challenges like poor health service engagement, impacting guideline adherence and patient management.

Methods: We retrospectively collected data from the electronic medical records of all CLD patients admitted to WH in 2021. We documented demographics, presenting complaints, underlying liver disease, adherence to varices screening, and treatment. Univariate and multivariable logistic regression assessed predictors of liver-related mortality, defined as death resulting directly from a CLD complication at a 2-year follow-up.

Results: Our study included 275 CLD patients (see Table 1 for characteristics), with 27 patients (9.5%) presenting with variceal bleeding. Of the 245 patients who met BAVENO criteria for variceal screening, 77.6% (n=190) underwent gastroscopy, revealing Grade 1 varices in 33.6% (n=43) and Grade 2/3 varices in 36.7% (n=47). Follow-up gastroscopy was scheduled for 56.7% (n=21) without initial varices and 75.6% (n=31) with Grade 1 varices. Among those with Grade 2/3 varices, 80.9% (n=38) underwent variceal banding, with 94.7% (n=36) receiving follow-up gastroscopy. 19.1% (n=9) patients were prescribed NSBB. Of the 27 variceal bleeding cases, 21 warranted varices screening, yet only 11 had prior gastroscopy. Within these, 6 patients had Grade 1 and 1 had Grade 2 varices. The Grade 2 varices were ligated but NSBB was not initiated.

Univariate regression showed a correlation between reduced liver-related mortality and variceal screening (OR 0.42, 95% CI 0.22–0.81, p=0.01) as an independent variable, confirmed by multivariate logistic regression after adjusting for confounders like age and Child-Pugh scores. Among unscreened patients, the most common cause of death was infection (n=10, 16.1%); only 4 had variceal bleeding with no resulting deaths. This is possibly due to selection bias, as high-risk patients with prior varices bleeding history were more likely to be connected to the service.

Conclusion: Our study shows that variceal screening reduces liver-related mortality, yet it also reveals deficiencies in the current clinical approach to screening and treating varices at WH. These deficiencies may arise from various challenges, including communication barriers such as language constraints or time limitations in outpatient clinics, as well as patient factors such as limited health literacy resulting in poor compliance. Efforts should be directed towards improving the uptake of varices surveillance and enhancing the utilization of NSBB among patients.

63

The risks and benefits of long term ascitic drains – experience from a single Australian centre

Richard Goodheart, Justin Chin, Adam Doyle, Nick Kontorinis, Jee Kong, Wendy Cheng and Tim Mitchell

Royal Perth Hospital, Perth, Australia

Background and Aim: Refractory ascites is a common complication of advanced chronic liver disease. Patients may not be suitable for transjugular intrahepatic portosystemic shunt (TIPS) or liver transplantation (LT), and hence require large volume paracentesis (LVP) to reduce their symptom burden. A long term ascitic drain (LTAD) has been postulated as an effective palliative measure to improve symptom control and reduce hospital admissions. LTAD is not considered standard of care, but it has been implemented globally in carefully selected patient groups. The aim of this study was to assess the outcomes of LTAD placement, focusing particularly on hospital presentation rates and complications.

Methods: All patient data for those who underwent LTAD insertion from 2020-2024 were collated by conducting a product search (RK001) within the Radiology Department Information System. Data was collated from medical records to determine the patient demographics, indications for LTAD and contraindications for TIPS or LT. Data on complications, hospital presentations and mortality were obtained.

Results: A total of 11 patients had LTAD inserted for refractory ascites in this period. Of the 11 LTAD, four patients developed complications, which included pain, drain blockage or infection (Table 1). Both patients with bacterial peritonitis had their drains removed and their infections treated. Case 8 had another drain inserted post infection to facilitate transfer to hospice. Three patients (27%) passed away within one week of drain placement (unrelated to drain placement), however all patients had multiple admissions to hospital in the preceding three months. This may represent a missed opportunity for LTAD insertion earlier in their disease course, when they may have benefited from earlier symptom control. The median (range) number of presentations to hospital in the three months prior to insertion of the LTAD was 4 (1 – 16). In the three months post LTAD insertion the median number of hospital presentations was 0 (0-5). This data is affected by the short follow-up period in multiple patients.

68

Hepatocellular carcinoma care during the COVID-19 pandemic: a single-centre experience – missing patients and robust screening

Nicholas Hannah^1,2,3, Michael Mil^1,2, James Haridy¹, Ashok Raj¹ and Siddharth Sood^2,3

¹The Royal Melbourne Hospital, Melbourne, Australia; ²The University of Melbourne, Melbourne, Australia; ³Northern Health, Melbourne, Australia

Background and aim: The COVID-19 pandemic challenged Australian healthcare systems, particularly in Melbourne, which endured the highest number of days in lockdown worldwide. Hepatocellular carcinoma (HCC), a leading cause of cancer mortality, relies on timely screening to improve patients’ treatment and prognosis. Pandemic-related disruptions, raised concerns about missed diagnoses and delayed presentations. We aimed to assess the pandemic's effect on HCC presentations at a tertiary referral centre.

Methods: This is a retrospective cohort analysis at a tertiary referral hospital in Melbourne, Australia which assesses pandemic effects on HCC diagnosis and management. New HCC cases presented at the HCC multidisciplinary meeting from March 2018 to February 2022 were divided into pre-pandemic (March 2018 – February 2020) and pandemic (March 2020 – February 2022) cohorts to compare presentations, diagnosis, stage, and treatments.

Results: There were 178 new HCC cases between March 2018 and February 2022. A 23.7% reduction in presentations occurred during the pandemic (n = 77) compared to pre-pandemic (n = 101). There was a significant decrease in symptomatic presentations; n = 21 (20.8%) pre-pandemic compared with n = 5 (6.5%) during pandemic, a proportionate decrease of 68.7% (p = 0.038). Incidental diagnoses, the majority, were stable n = 54 (53.4%) and n = 45 (58.4%) respectively. Screen-detected presentations were also stable n = 24 (23.8%) pre-pandemic and n = 25 (32.5%) during the pandemic. No demographic differences emerged between cohorts. There was a significant increase observed in pandemic years in viral-related liver diseases from 23 (22.8%) to 32 (41.6%) p = 0.007. Significant changes were seen in method of diagnosis with an increase in utilisation of MRI and biopsy with a corresponding decrease in CT being the sole diagnostic modality (p <0.0001). No differences in disease stage, tumour characteristics, or treatment were observed.

Conclusion: We witnessed a decline in HCC presentations during the pandemic. This appears due to a decrease in symptomatic presentations with preservation of screen-detected HCC, despite changes to care delivery. We noted a rise in viral mediated HCC and increased utilization of MRI and biopsy for diagnosis and staging. It remains unclear if the reduction in symptomatic presentations was a result of care-diversion to other centres or a true reduction in cases, given similar international findings. Further research is required to understand this effect and whether there will be consequences in the coming years.

69

A systematic review and meta-analysis of prostate-specific membrane antigen (PSMA) PET/CT in the diagnosis and staging of hepatocellular carcinoma (HCC)

Nicholas Hannah^1,2,3, Catherine Yu³, Leya Nedumannil³, Erica Hately³, James Haridy¹, Grace Kong⁴, Alex Boussioutas^2,4,5,6 and Siddharth Sood^2,3

¹The Royal Melbourne Hospital, Melbourne, Australia; ²The University of Melbourne, Melbourne, Australia; ³Northern Health, Melbourne, Australia; ⁴Peter MacCallum Cancer Centre, Melbourne, Australia; ⁵Monash University, Melbourne, Australia; ⁶Alfred Health, Melbourne, Australia

Aim: To assess the efficacy of PSMA PET in detecting and accurately diagnosing HCC lesions meeting histological or quantitative imaging criteria according to the Liver Imaging Data Reporting System (LIRADS) on contrast-enhanced CT or MRI.

Methods: We included randomized clinical trials, prospective and retrospective cohort studies, observational studies, and case series, while excluding case reports. A comprehensive search of Medline, EBMASE, CINAHL, Cochrane CENTRAL, and Web of Science was conducted up to November 30, 2023. The quality assessment tool QUADAS-2 was utilised, Screening and data abstraction was carried out by two reviewers, with a third reviewer arbitrating any discrepancies.

Results: Ten studies were included in this review (9 prospective cohort studies, 1 retrospective), encompassing 201 patients, including 28 females, with a total of 491 lesions identified on baseline imaging. All studies utilized a quantitative diagnostic approach, either histological diagnosis or LIRADS. Nine studies used ⁶⁸Ga-PSMA-11 radioisotope, one used ¹⁸F-PSMA-1007. Eight studies provided adequate data for per-lesion analysis, yielding a pooled sensitivity of 93.9% (95% CI 83.2 – 98.0); specificity was poorly reported, with only three studies reporting sufficient data. At the per-patient level, all ten studies provided were analysed, with a sensitivity of 89.3% (95% CI 78.9 – 94.9), specificity was again poorly reported with insufficient data. Among the three studies with adequate data for full per-lesion meta-analysis, n = 115 lesions in n = 41 patients, sensitivity was 97.1% (95% CI 87.8 – 99.4), while specificity was 42.2% (95% CI 0.3 – 99.4). Two studies provided sufficient data for meta-analysis on a per-patient level (n = 50 patients) demonstrating a sensitivity of 92.5% (95% CI 64.0 – 98.9), specificity of 72.4% (95% CI 1.3 – 99.8). Seven studies exhibited a high risk of bias in at least one domain of the QUADAS-2 assessment, with five indicating a high risk of bias in the index test domain, concerns regarding the applicability of included studies were low.

Conclusions: PSMA PET demonstrates a high sensitivity for HCC and shows promise as an imaging modality for the staging, diagnosis, and management of HCC. Existing literature does not provide enough data to confidently evaluate specificity or accuracy. Further prospective studies are necessary to better define these parameters. Studies such as Hepatocellular Carcinoma Imaging Using PSMA PET/CT (HepaSMART) (NCT05095519) aim to better determine the sensitivity and specificity of PSMA PET for HCC.

74

Semaglutide improves cardiovascular outcomes in patients with high risk of metabolic dysfunction-associated steatohepatitis – a subgroup analysis from the SELECT trial

Jacob George^1,2,3, Sebastian Meyhöfer^4,5, Bertrand Cariou⁶, Cintia Cercato⁷, Helen Colhoun⁸, Anne Katrine Duun-Henriksen⁹, Iris Kliers⁹, A Michael Lincoff¹⁰, Ildiko Lingvay¹¹, Michelle Long^9,12, Philip N Newsome¹³, Stephen Nicholls¹⁴, Maria De Los Angeles Quiroga Pelaez⁹, Ferruccio Santini¹⁵, Arun J Sanyal¹⁶ and Steven Kahn¹⁷

¹Storr Liver Centre, Westmead Institute For Medical Research, Sydney, Australia; ²Department of Gastroenterology & Hepatology, Westmead Hospital and Sydney West Local Health District, Sydney, Australia; ³Medical School, University of Sydney, Sydney, Australia; ⁴Clinical, Medical & Regulatory, Novo Nordisk Pharma GmbH, Mainz, Germany; ⁵Department of Internal Medicine 1 - Endocrinology & Diabetes, University Medical Centre Lübeck, Lübeck, Germany; ⁶CHU Nantes, CNRS, INSERM, l’Institut du thorax, Nantes Université, Nantes, France; ⁷Obesity Unit, Department of Endocrinology, Hospital das Clínicas, University of São Paulo, Brazil; ⁸Institute of Genetics and Cancer, The University of Edinburgh, UK; ⁹Novo Nordisk A/S, Søborg, Denmark; ¹⁰Department of Cardiovascular Medicine, Cleveland Clinic and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, USA; ¹¹Department of Internal Medicine/Endocrinology and Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, USA; ¹²Department of Medicine, Section of Gastroenterology, Boston University Chobanian & Avedisian School of Medicine, Boston, USA; ¹³King’s College London and King’s College Hospital, Institute of Hepatology, London, UK; ¹⁴Victorian Heart Institute, Monash University, Melbourne, Australia; ¹⁵Obesity and Lipodystrophy Centre, University Hospital of Pisa, Pisa, Italy; ¹⁶Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, USA; ¹⁷Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, USA

Background and Aim: Cardiovascular (CV) risk is increased in people living with metabolic dysfunction-associated steatohepatitis (MASH). Although liver biopsy remains the gold standard to diagnose MASH, it is not practical to implement on a large scale. However, non-invasive tests, such as the Fibrosis-4 score (FIB-4), are useful for staging patients with fibrotic MASH and predict overall, CV- and liver-related mortality. In the SELECT CV outcome trial, which included patients with a body mass index ≥27.0 kg/m² and established CV disease but without diabetes, those treated with the glucagon-like peptide-1 receptor agonist semaglutide had a 20% CV risk reduction compared with those receiving placebo. We examined the CV benefits of semaglutide in a subgroup of participants at high risk of MASH as defined by FIB-4.

Methods: SELECT was a multicentre, randomised, double-blind, placebo-controlled, event-driven trial in 17,604 patients aged ≥45 years. Patients were randomised 1:1 to receive once-weekly subcutaneous semaglutide 2.4 mg or placebo in addition to standard of care recommendations for CV disease prevention. This subgroup analysis for the primary composite endpoint of 3-point major adverse cardiovascular event (MACE; non-fatal myocardial infarction, non-fatal stroke, CV death) was performed for patients with increased MASH risk as indicated by FIB-4 ≥1.3 for patients aged <65 years and FIB-4 ≥2.0 for patients ≥65 years, and for a second subgroup of patients of any age with FIB-4 >2.67. As identified by review of medical history and co-medication, patients with a cause of liver disease other than MASH were not included in this analysis.

Results: From the SELECT cohort, 3665 patients (20.8% of all) aged <65 years with FIB-4 ≥1.3 or aged ≥65 years with FIB-4 ≥2.0 were included in this analysis. The primary CV endpoint occurred in 140 of the 1834 patients (7.6%) in the semaglutide group and in 176 of the 1831 patients (9.6%) in the placebo group (hazard ratio [HR] 0.79; 95% confidence interval [CI]: 0.63;0.98; p<0.03). In the subgroup of 475 patients with suspected MASH and advanced fibrosis (FIB-4 >2.67 irrespective of age), there were 22 CV events in 235 patients treated with semaglutide 2.4 mg compared with 35 events in 240 placebo-treated patients, yielding an HR of 0.64 (95% CI: 0.37;1.08; p=0.10).

Conclusion: In line with the primary analysis of the SELECT trial, use of semaglutide 2.4 mg in a subgroup of patients at high risk of fibrotic MASH as defined by FIB-4 produced a 21% reduction in MACE outcomes.

75

Impact of distance from liver transplant centre on outcomes following liver transplantation: an Australian single centre study

Simone Chin^1,2, Charlotte Kench^1,2, Rena Cao¹, Christina Lee¹, Karen Waller^2,3, Susan Virtue¹, Claire West¹, Talal Valliani¹, David Bowen^1,2, Rachael Jacob¹, Madeleine Gill^1,2, Carlo Pulitano^1,2, Michael Crawford^1,2, Simone Strasser^1,2, Geoffrey McCaughan^1,2,3 and Ken Liu^1,2,3

¹Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, Australia; ²Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; ³Liver Cancer and Injury Group, The Centenary Institute, The University of Sydney, Sydney, Australia

Background and Aim: Access to liver transplantation (LT) is affected by geographic disparities. Higher waitlist mortality is observed in patients residing further away from LT centres but impact of distance on post-LT outcomes is unclear. We aimed to evaluate whether the distance LT recipients reside from their LT centre impacts on graft and patient outcomes.

Methods: We retrospectively studied consecutive adults who underwent deceased-donor LT from 2006-2021 at Royal Prince Alfred Hospital (RPAH), the only LT centre in the state of New South Wales (NSW), Australia. The state covers an area of 801,150km². Those residing outside of NSW at time of transplant were excluded. Donor and recipient data were collected from a prospective LT database. Patients’ regional area code (0 = least remote, 4 = most remote) and socioeconomic code (1 = relatively greater disadvantage, 5 = relative lack of disadvantage) were obtained from the Australian Bureau of Statistics. Patients were grouped based on their distance from LT centre at time of transplant (≤100km vs. >100km). For survival analyses, patients were censored if they moved to a new residential address during follow-up.

Results: During the study period, 973 patients underwent LT (69.7% male, median age 55.6 years (IQR 49.0-60.6)). The median distance from patient residence to LT centre was 44.9km (IQR 21.9-168.0). 64.2% of patients lived ≤100km from RPAH. 77.6% of patients were from regional area code 0. The distribution of LT recipients across the five socioeconomic codes was similar (17.9-20.2%). Compared to patients living ≤100km from RPAH, those living >100km away were less likely to: be male (64.0% vs. 72.7%, p = 0.004); have chronic hepatitis B (3.5% vs. 12.6%, p = 0.001) or viral hepatitis (35.7% vs. 42.2%, p = 0.049) as their cause of liver disease; or have hepatocellular carcinoma as their primary indication for LT (23.3% vs. 32.1%, p = 0.004). Patients living >100km away had higher body mass indices (27.1 vs. 26.0 kg/m², p = 0.01) compared to those living closer. At a median follow-up of 47.1 months (IQR 13.5-93.7), there were 190 deaths and 42 retransplants. Living >100km from the LT centre was associated with fewer face-to-face clinic visits in the first year after LT (10 vs. 11 visits, p < 0.001) and fewer overall readmissions to the LT centre (32.4% vs 67.6%, p < 0.001). Distance from LT centre, regional code, and socioeconomic code did not impact on long-term graft or patient survival based on Kaplan-Meier survival analysis (Log-Rank p all >0.1). There was a trend towards increased likelihood of biopsy-proven rejection in patients living >100km away (p = 0.069).

Conclusion: In this single centre Australian study, patients living further away from their LT centre had different demographics and fewer face-to-face visits during follow-up. Despite this, distance from the LT centre was not associated with long-term inferior graft or patient survival post-LT.

80

Flinders Albumin in the Home (FAITH): A feasibility study

Kylie Bragg¹, Rachel Wundke¹, Sumudu Narayana¹, Kate Muller¹, Jeyamani Ramachandran¹, Jodie Altschwager², Russell Hunt¹ and Alan Wigg¹

¹Flinders Medical Centre, Adelaide, Australia; ²Metropolitan Referral Unit, Adelaide, Australia

Background and Aims: Long term administration of human albumin (HA) has been shown to be beneficial in patients with ascites due to decompensated cirrhosis (DC) providing improved ascites control, improved renal function, reduced hospitalization and improved mortality. However, its implementation is limited by bed availability at hospitals or infusion suites. This pilot study was undertaken to assess the feasibility of home administration of HA in the management of DC. Secondary aims were to assess the safety, efficacy, acceptability, and comparative costs of home administration of HA.

Methods: The study commenced recruitment in November 2023 with a planned follow up of 6 months. Key inclusion criteria were patients with DC with ascites, hepatic hydrothorax or peripheral oedema not diuretic controlled. Key exclusion criteria were patients with known heart failure and lack of cognitive capacity. A community nursing service visited the patient, obtained IV access, and administered HA as per the following protocol (loading dose of Alburex 40g twice a week the first 2 weeks, then 40g weekly, with each 100 ml bottle of albumin infused over at least 45 minutes). A case conference with a panel of Hepatologists was held at 3 months to determine futility or effectiveness of infusions. Patients were surveyed with a questionnaire at the end of study.

Results: Fourteen patients consented to the study and their demographics are shown in Table 1. To date 14 participants have received home HA infusions with median (IQR) study follow up time of 10 (9) weeks, with four participants completing the planned 3-month course of home HA infusions. The most common (86%) reason for study inclusion was ascites not controlled by diuretics.

Feasibility: All patients who commenced successfully received HA infusions at home. The median time of each home visit and per bottle of albumin infusion was 2.7 hours (IQR 11 minutes) and 47.5 minutes (IQR 1.2 minutes), respectively. Fifty percent (50%) of participants required a peripherally inserted central catheter insertion at commencement or during the study.

Safety and efficacy: There were no reported treatment-related adverse events. The 3-month course of albumin was adjudicated to be clinically effective in all four participants who have currently reached the 3-month study point and HA was continued in these patients. The median (IQR) albumin score at study entry and at 3 months was 27 (IQR 3.8) and 40 (IQR 5.8), respectively.

Participant acceptability: There was good participant acceptability with no patient withdrawals or requests for hospital-based HA infusions.

Cost comparison: The costs of home versus hospital-based HA infusion visits were estimated at $AUD 408 versus $AUD 537, respectively.

Conclusion: HA administration at home appears feasible, safe, effective and has high participant acceptability relative to hospital-based infusions. HA may provide a logistical and cost effective option to administer albumin in cirrhosis. Larger studies validating our pilot study findings are indicated.

82

Cholestasis gene testing – analysis of requesting patterns at a single centre

Richard Goodheart, Wendy Cheng, Adam Doyle, Nick Kontorinis, Jee Kong, Justin Chin and Tim Mitchell

Royal Perth Hospital, Perth, Australia

Background and Aim: With the availability of next generation sequencing, genetic disorders of cholestasis are increasingly being diagnosed as a cause of chronic or episodic liver disease in adults. Indications for genetic cholestasis testing in adults have not been established as phenotypic presentations may vary. In this study, we reviewed the use of cholestasis genetic test at a single Australian centre. Additionally, we reviewed whether cholestasis gene testing was diagnostic in patients with cryptogenic liver disease without known risk factors for genetic disorders of cholestasis.

Methods: This was a retrospective study conducted at a single tertiary referral centre. All patients who had the cholestasis genetic panel requested since 2018 were collated from the local pathology department. From this list, medical records were reviewed to collect patient demographics, investigation results, indications for genetic testing, and probable aetiology. Cryptogenic liver disease was defined as chronic liver disease without identifiable cause on standard assessment (parenchymal liver screen, imaging +/- liver biopsy) and the absence of an established risk factor for genetic disorder of cholestasis.

Results: A total of 26 patients had cholestasis genetic tests requested. Of these, 77% were females with an age range of 17 to 88. One result is still pending. Of the remaining 25 patients, three (12%) had a positive result confirming genetic cholestasis. Each of these positive cases involved the ABCB4 gene, however the mutation type and clinical phenotypes differed between them. One patient was a 34-year-old female with recurrent postpartum cholestasis; her genetic studies showed a heterozygous ABCB4 mutation (c.3280-2A>G). The second patient was a 20-year-old female with cholangitis and imaging demonstrated intrahepatic stones. She had a strong family history of biliary pathology, and her genetic testing demonstrated an ABCB4 heterozygous mutation (c.2380G>C) in keeping with her low phospholipid-associated cholestasis (LPAC). The last patient was a 53-year-old female with chronic cholestasis associated with gallstone disease, ICP and a family history of liver disease. Her genetic testing showed a compound heterozygous mutation in ABCB4 (c.2888T>C(;)2966A>C).

Cryptogenic liver disease was one of the most common documented indications for testing. However, no case yielded a positive result (Figure 1).

Conclusion: Genetic cholestasis is an uncommon but important cause of chronic liver disease. The phenotypical presentation varied greatly between patients despite mutations only occurring in the ABCB4 gene in this study. Our study suggests cryptogenic liver disease in the absence of a specific risk factor for genetic cholestasis is unlikely to yield a positive result.

83

Worsening rates of reinfection amongst patients treated for HCV in the Western Australian prison system

Richard Goodheart, Wendy Cheng and Adam Doyle

Royal Perth Hospital, Perth, Australia

Background and Aim: Despite highly effective direct-acting antiviral therapy (DAA), hepatitis C virus (HCV) continues to be a prominent health issue amongst incarcerated Australians, with the seroprevalence estimated at about 20%. Anecdotally it has been noted that more prisoners are presenting with re-infections. The aim of this study was to assess the trends of HCV treatment amongst Western Australian prisoners, specifically focusing on the changing proportion of patients presenting despite prior treatment over time.

Methods: We performed a prospective study of all prisoners treated for HCV at a Western Australian tertiary hospital since 2017. Data was collected from every treated patient including their demographics, cirrhosis status, prior treatment exposure, treatment choice and treatment response. Trends over time were analysed between treatment-naïve and treatment-experienced patients. Patients with confirmed re-infections were also analysed (defined by either having genotype switching or previously confirmed sustained virological response at 12 weeks (SVR12)).

Results: A total of 622 patients were reviewed between 2017 and 2024. Of these, 487 (78.3%) were treatment-naïve and 135 (21.7%) were treatment-experienced. Of these treatment-experienced patients, 43 (31.9%) had confirmed evidence of re-infection. 328 patients had follow-up data and of that group, 93.6% achieved SVR12. There was a statistically significant difference between gender, with more males being treatment-experienced. Regarding trends over time, there was a statistically significant increase in the proportion of patients who were treatment-experienced over time, with the odds of being treatment-experienced increasing by 45% every year (OR = 1.45, 95% CI (1.31 – 1.61)). Treatment-experienced patients have represented more than 40% of the cohort each year since 2022, compared to only 6% of the cohort in 2017. Similarly, there was also a statistically significant increase in confirmed cases of reinfection over time, with a 77% increased odds of having a reinfection for each year (OR = 1.77, 95% CI (1.47 – 2.14)).

Conclusion: There has been a significant increase in the number of treatment-exposed prisoners with HCV over this 7-year period. Although only 31.9% of patients who were treatment-experienced had confirmed reinfection, it is likely that this data under-reports reinfections, given the effectiveness of current DAA regimens. This increasing reinfection rate over time shows that the current approach to treating prisoners with HCV is inadequate in the effort to eradicate HCV. Harm minimisation strategies, and wide-scale treatment approaches such as point of care testing blitzes may be needed to help reduce the endemic of HCV within our prison system.

85

Broadening perspectives: the importance of thinking outside the liver

Shauna Madigan and Wayne Rankin and Darren Mounkley and Edmund Tse

Flinders Medical Centre, Adelaide, Australia

Introduction: Patients are routinely referred to hepatology clinic with non-specific changes to their liver function tests (LFTs). Often LFT derangements are not caused by primary liver pathology, and it is important to be cognisant of this to avoid delayed diagnosis and unnecessary invasive investigations.

Case report: An 18 y.o. patient was referred to hepatology clinic for an incidental finding of LFT derangement. She was asymptomatic and past medical history was significant only for anxiety. She had a family history of Wilson’s disease. Her LFTs showed a hepatocellular picture with alanine aminotransferase (ALT) of 296 u/L, aspartate aminotransferase (AST) of 287u/L and lactate dehydrogenase (LDH) of 681u/L, the other liver enzymes including bilirubin were within normal limits. Looking back through pathology records her LFTs had shown a similar pattern for about 12 months. She had not started any new medications or herbal supplements. Routine liver screen for viral and autoimmune causes was unremarkable. 24-hour urine copper was within normal limits. There were no structural changes noted on liver imaging. She had a liver biopsy which was unremarkable. Creatinine kinase (CK) was added to her blood tests and was elevated at 1236 u/L (0-150 u/L normal range). This raised suspicion for a myopathy and through metabolic and genetic testing she and her fraternal twin (who was also referred to hepatology clinic) were diagnosed with Pompe disease. Pompe disease or acid alpha glucosidase (GAA) deficiency is a glycogen storage disease which leads to accumulation of glycogen within the lysosome in all tissues. It is a rare autosomal recessive neuromuscular disorder with an incidence of 1 in 40,000 in Denmark and 1 in 146, 000 in Australia.[1] The condition can be both infantile or late onset. Clinical spectrum can vary but usually includes skeletal myopathy and in severe cases this can lead to respiratory failure. Elevations of CK, LDH, ALT and AST are commonly seen.[2] Enzyme replacement has become available in the last decade which has significantly improved survival.

Conclusion: This case demonstrated the importance for hepatologists to think outside of the liver for causes of LFT derangement and have an awareness of conditions such as GAA and other glycogen storage disorders. It also illustrates the need for continued investigation even when the liver biopsy is unremarkable. This case supports the inclusion of tests such as CK as part of an extended liver screen.

References

1. Van der Ploeg, A.T. and A.J.J. Reuser, Pompe's disease. The Lancet, 2008. 372(9646): p. 1342-1353.

2. Kohler, L., R. Puertollano, and N. Raben, Pompe Disease: From Basic Science to Therapy. Neurotherapeutics, 2018. 15(4): p. 928-942.

86

A “perhexling” case of liver cirrhosis

Elaine Koh¹, Vikram Rao¹, Gordon Chen¹, Ian Simpson² and Marcus Robertson¹

¹Gastroenterology Department, Peninsula Health, Frankston, Australia; ²Pathology Department, Monash Health, Melbourne, Australia

Introduction: Perhexiline was developed as an anti-anginal drug in the 1970s. It continues to be prescribed in Australia and New Zealand for refractory angina, although its use has diminished worldwide due to its significant side-effect profile. With emerging evidence of potent anti-cancer properties, there is a current resurgence of interest in perhexiline. We present a case of perhexiline-induced liver cirrhosis which occurred within 12-months of drug commencement.

Case report: A 69-year-old Caucasian gentleman presented to a tertiary centre in December 2023 with first-presentation decompensated liver cirrhosis, manifesting as large volume ascites and variceal bleeding. His past history was significant for ischaemic heart disease, dyslipidaemia and hypertension with no history of liver disease. His medications included aspirin, clopidogrel, carvedilol, rosuvastatin, nicorandil and isosorbide mononitrate, with perhexiline therapy initiated approximately 12-months prior. The patient was pre-morbidly fit and well, and worked as a welder. He was a non-smoker, with a BMI of 23 and had no history of alcohol misuse. There was no family history of liver disease. During his admission, a liver ultrasound and CT abdomen and pelvis demonstrated liver cirrhosis and portal hypertension, with no focal hepatic lesions and patent hepatic vasculature. Of note, previous abdominal imaging in 2020 showed no features of chronic liver disease. A full liver screen was unremarkable, and grade II oesophageal varices were detected at gastroscopy. A percutaneous liver biopsy was performed (Figure 1), which demonstrated micro-nodular cirrhosis and very extensive ballooning degenerative change with Mallory's hyaline formation, but only scant or absent steatosis. On review of the patient’s biopsy, the pattern was noted to be typical of alcohol-related liver cirrhosis; however, given a corroborated history of lifelong minimal alcohol use and nominal risk factors for metabolic-associated steatotic liver disease, other differential diagnoses were considered. It was noted that the patient’s liver biopsy findings were highly compatible with perhexiline-induced cirrhosis, and his perhexiline was ceased indefinitely.

Discussion: Perhexiline acts by shifting myocardial metabolism from fatty acid to glucose utilisation, resulting in improved myocardial efficiency. Although effective for angina, its clinical use was limited by a narrow therapeutic index and high pharmacokinetic variability. Perhexiline is metabolised by the CYP2D6 pathway. Variable expression and/or mutations in CYP2D6 can result in highly variable clearance rates, causing toxic drug concentrations in poor metabolisers. These poor metabolisers include 7-10% of the Caucasian population. Severe neurotoxicity and hepatoxicity were described in poor metabolisers in the late 1970s; often associated with severe weight loss, peripheral neuropathy and hypoglycaemia. Histologically, perhexiline-induced cirrhosis manifests as ‘pseudo-alcoholic hepatitis’. Hallmarks of this include hepatocyte ballooning, Mallory bodies, hyaline necrosis as well as lamellar lysosomal inclusion bodies representing phospholipidosis. Triglyceride and fatty acid accumulation are also common features.

Conclusion: Administration of perhexiline may result in iatrogenic cirrhosis within 9-months in poor metabolisers, which mimics alcohol-related hepatitis and cirrhosis on liver biopsy. Careful monitoring is recommended in all patients prescribed perhexiline.

90

Phase 3 randomised, placebo-controlled ESSENCE trial of semaglutide 2.4 mg in participants with non-cirrhotic non-alcoholic steatohepatitis: baseline characteristics, impact of new metabolic dysfunction-associated steatotic liver disease criteria and non-invasive tests

Jacob George^1,2,3, Philip N Newsome⁴, Elisabetta Bugianesi⁵, Vlad Ratziu⁶, Mary E Rinella⁷, Michael Roden^8,9,10, Kristiane A Engebretsen¹¹, Iris Kliers¹¹, Laura Østergaard¹¹, Denise Vanni¹¹, Jeppe Zacho¹¹ and Arun J Sanyal¹²

¹Storr Liver Centre, Westmead Institute For Medical Research, Westmead, Sydney, Australia; ²Department of Gastroenterology & Hepatology, Westmead Hospital and Sydney West Local Health District, Westmead, Sydney, Australia; ³University of Sydney Medical School, University of Sydney, Sydney, Australia; ⁴National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; ⁵Department of Medical Sciences, University of Turin, Turin, Italy; ⁶Institute for Cardiometabolism and Nutrition, Hospital Pitié-Salpêtrière, Sorbonne Université, Paris, France; ⁷Department of Medicine, University of Chicago, Chicago, USA; ⁸Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; ⁹German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany; ¹⁰Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; ¹¹Novo Nordisk A/S, Copenhagen, Denmark; ¹²Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, VCU School of Medicine, Richmond, USA

Background and Aims: We report baseline characteristics of participants randomised in the ESSENCE trial of the glucagon-like peptide-1 analogue semaglutide 2.4 mg subcutaneous once weekly (OW) for non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH).

Methods: ESSENCE (NCT04822181) is an ongoing 247-week, phase 3, randomised trial. Following 14 weeks’ screening, 800 participants (part 1) of 1200 planned (part 2) with MASH and fibrosis stages 2/3 (F2/F3) were randomised 2:1 to receive semaglutide 2.4 mg subcutaneous OW or placebo OW added to standard of care. In part 1, the two primary endpoints at 72 weeks are resolution of steatohepatitis and no worsening of liver fibrosis, and improvement in liver fibrosis and no worsening of steatohepatitis. Based on a central pathologist evaluation, inclusion criteria were histological presence of steatohepatitis stages F2/F3 per the Nonalcoholic Steatohepatitis Clinical Research Network classification, and a non-alcoholic fatty liver disease activity score (NAS) of ≥4, with a score of ≥1 in steatosis, lobular inflammation and hepatocyte ballooning.

Results: 800 participants (250 F2; 550 F3) were randomised. Mean (SD) age was 56 (11.6) years; 57.1% were female; ≥99% had ≥1 cardiometabolic risk factor(s) in accordance with the metabolic dysfunction-associated steatotic liver disease (MASLD) definition. Mean (SD) NAS was 5.05 (0.95), and higher in F3 versus F2 (5.11 [0.95] vs 4.92 [0.93], respectively). Participants with NAS ≥5 had more cardiometabolic risk factors for MASLD (52.9%) versus NAS 4 (45.3%). Similarly, 52.9% of participants with F3 had all five cardiometabolic risk factors versus 44.8% with F2. Although cardiometabolic comorbidities were highly prevalent, 44.5% and 27.3% of participants did not have type 2 diabetes (T2D) and obesity, respectively. Normal liver transaminases were observed in 26.3% of participants. Mean (SD) FibroScan liver stiffness was 12.8 (6.9) kPa; 15.3% of participants had values <8 kPa. Mean (SD) controlled attenuation parameter value was 329 (46) dB/m; enhanced liver fibrosis (ELF) score was 10.0 (1.0) and 43.5% of participants had an ELF score of <9.8. 8.8% and 9.0% of participants with/without T2D did not meet any of the following non-invasive criteria: Fibrosis-4 index ≥1.3, vibration-controlled transient elastography ≥8.1 or ELF ≥9.8; more participants with F2 (14.7–16.4%) did not meet these criteria versus F3 (4.5–6.7%).

Conclusion: The ESSENCE baseline population includes participants with significant fibrosis (F2 and F3); ~91% of the population had ≥1 positive diagnostic non-invasive test. Cardiometabolic risk factors were found in ≥99% of participants, and in increased numbers in those with higher NAS and fibrosis stages.

96

Frailty predicts multiple negative clinical outcomes in patients referred for liver transplantation

Heidi Johnston^1,3,4, Melita Andelkovic^2,3, Hannah Mayr^1,4,5, Tahnie Takefala^1,3, Yanyan Chen⁶, Aaron Thrift^6,7, Ingrid Hickman^1,4,8 and Graeme Macdonald^2,3,4

¹Department of Nutrition and Dietetics, Brisbane, Australia; ²Department of Gastroenterology and Hepatology, Brisbane, Australia; ³Queensland Liver Transplant Service, Princess Alexandra Hospital, Brisbane, Australia; ⁴The Faculty of Medicine, University of Queensland, Brisbane, Australia; ⁵Centre for Functioning and Health Research, Metro South Health, Brisbane, Australia; ⁶Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, USA; ⁷Dan Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, USA; ⁸ULTRA Team, The University of Queensland Clinical Trial Capability, Brisbane, Australia

Background: Frailty is associated with mortality in patients referred for liver transplant (LT) but the impact on other clinical outcomes is less clear. We investigated the impact of frailty (liver frailty index, LFI) on likelihood of receiving a LT, unplanned hospitalizations and peri-LT ICU/hospital length of stay (LOS).

Methods: Between May 2018-Sept. 2022, adults with cirrhosis referred for LT had their LFI determined at their initial dietitian appointment. Clinical outcomes included receiving a LT, waitlist mortality, pre-LT unplanned hospitalizations (excluding booked procedures like paracentesis), and peri-LT ICU/hospital LOS. Chi²/Mann-Whitney U tests, Kaplan-Meier, Cox proportional hazards model and competing risk analysis were performed to explore associations between LFI and clinical outcomes.

Results: In 266 patients (75% male, median age 58 [IQR 50-63]; median MELD 16 [11-19]), the median LFI was 3.7 [3.3-4.1]. 19% of patients were robust, 68% pre-frail, and 14% frail. 144 (54%) patients received a LT. The LFI was significantly better in LT recipients (3.6 [3.3-4.0]) than in those not transplanted (3.8 [3.4-4.2], p=0.02, Table 1). Frail and pre-frail patients were less likely to receive a LT than robust patients (HR 0.63, 95%CI 0.5-0.9, p=0.04). After adjusting for confounders (age, sex, HCC presence, MELD), every 1-point increase in the LFI was associated with a 29% decrease in the likelihood of LT (HR 0.71, 95%CI 0.54-0.94, p=0.02). Competing risk analysis found that every 1-point increase in LFI was associated with a 90% increased risk of waitlist mortality (HR 1.9, 95%CI 1.3-2.7, p<0.001). This was not seen for other reasons for not progressing to LT. The risk of waitlist mortality was almost 5-fold higher for frail compared to robust patients (HR 4.92, 95%CI 1.8-13.5, p=0.002). LFI was significantly worse in patients with unplanned hospitalizations with every 1-point increase in LFI associated with a 42% increased risk of unplanned hospitalization (HR 1.42, 95%CI 1.1-1.9, p=0.02). At the time of LT, baseline LFI was associated with prolonged ICU LOS but not hospital LOS with a 1-point increase in the LFI associated with a 3.2-fold (95%CI 1.1-9.8) increased odds of having an ICU LOS >4days.

Conclusions: In patients referred for LT, frailty increases the risk of not receiving a LT, waitlist mortality, pre-LT unplanned hospitalization and prolonged ICU LOS at the time of LT.

99

Patient and clinician views on telehealth for hepatitis B care: a qualitative study

Marvad Ahad^1,2, Jack Wallace^1,3, Susanne Glasgow⁴, Bradley Whitton⁴, Kate New⁴, Alexander Thompson^4,5, Amanda Wade^1,2,6, Joseph Doyle^1,2,5,7 and Jessica Howell^1,2,4,5

¹Burnet Institute, Melbourne, Australia; ²Monash University, Melbourne, Australia; ³La Trobe University, Melbourne, Australia; ⁴St Vincent's Hospital Melbourne, Melbourne, Australia; ⁵University of Melbourne, Melbourne, Australia; ⁶Barwon Health, Geelong, Australia; ⁷Alfred Hospital, Melbourne, Australia

Background and Aim: Telehealth services allow healthcare to be delivered without the need for in-person attendance by using information technology. While telehealth has been in use for delivering care in many settings, including for hepatitis B care, the COVID-19 pandemic has resulted in its wider application. Hepatitis B affects people from culturally and linguistically diverse backgrounds in Australia with improvements to access and engagement in care being necessary for national and global elimination targets to be met. Telephone and video consults can help improve clinic attendance rates and increase engagement in care, however this is at the loss of direct patient and healthcare worker contact. This qualitative study explored patient and healthcare worker views on the acceptability, perceived challenges, and benefits of telehealth technologies for care and treatment for people with hepatitis B.

Methods: Semi-structured interviews were conducted with patients (n=20) receiving hepatitis B care from a metropolitan hepatology clinic in Melbourne, Australia. Data were triangulated with semi-structured interviews with individual clinicians (n=11) and a focus group with clinicians (n=11). Data from interviews was thematically analysed using an inductive method.

Results: Three themes were identified: 1) telehealth impacts communication and rapport, 2) telehealth is convenient and suitable for patients living with hepatitis B, and 3) operational and systematic requirements for effective telehealth use. Both clinicians and patients reported in-person consultations had the benefit of non-verbal communication, with video preferred over telephone consultations. While patients reported little to no changes to relationships with their doctors, clinicians noted changes in the formality and tone of telehealth consultations. Factors contributing to the convenience of telehealth services for patients included the removal of the need for travel, taking leave from work, arranging care for other family members, and avoiding clinic waiting rooms. Barriers identified to telehealth included difficulty understanding clinicians either due to patient language barriers, limited familiarity with technology, and technical issues.

Conclusion: Despite some limitations to communication and establishment of rapport, clinicians and patients supported the continued use of telehealth for the provision of hepatitis B care, with video preferred over telephone consultations. Most patients reported positive experiences with telehealth consultations and reported convenience as its greatest advantage. These findings support telehealth as an acceptable tool to improve systematic access to and retention in hepatitis B care.

108

Use of beta blockers in compensated cirrhosis meeting Baveno-VII criteria: Real world outcomes

Darshan Nitchingham¹, Mohamed Asif Chinnaratha² and Dharshan Sathananthan²

¹Royal Adelaide Hospital, Adelaide, Australia; ²Lyell McEwin Hospital Department of Gastroenterology and Hepatology, Adelaide, Australia

Background and Aim: The Baveno-VII consensus is a non-invasive tool to predict clinically significant portal hypertension (CSPH) in patients with compensated cirrhosis. Patients having a median stiffness of >25 kPa, or 20-25 kPa AND platelet count <150 x 10⁹ on liver stiffness measurements (LSM) are considered to have CSPH and are at higher risk of developing decompensation. Recent evidence suggests that non-specific beta blockers reduce the risk of decompensation in this cohort of patients (PREDESCI trial)¹. Prior to this study, beta blockers were commenced only in a small number of patients whose screening endoscopy showed medium to large gastro-oesophageal varices. Our primary aim in this study is to compare the decompensation free survival between those who were on, and not on beta blockers in patients meeting the Baveno-VII criteria. Secondary aims include: (i) to compare the time to decompensation between the two groups and (ii) proportion of patients who were commenced on beta blockers.

Methods: Data on consecutive patients with compensated cirrhosis, diagnosed based on LSM, at a single tertiary referral centre from 14/7/2016 to 1/8/2023 were collected retrospectively. Patients with decompensated cirrhosis prior to LSM were excluded. Patients were followed-up till the first episode of decompensation or the end of study follow-up (29/02/2024), whichever happened first. Time to decompensation was calculated from the date of endoscopy to the first episode of decompensation.

Results: A total of 308 patients were screened for inclusion. After excluding patients not meeting Baveno-VII criteria for CSPH or decompensating prior to initial LSM, 249 patients were included for final analysis (61.8% males, median age (IQR): 58 (14) years). The aetiology of cirrhosis was predominantly chronic hepatitis C (34.5%), Non-alcoholic fatty liver disease (22.9%) and Alcoholic liver disease (14.5%). Median (IQR) follow-up in this cohort was 4.4 (3.6) years. Screening endoscopy was performed in 107 (42.6%) patients and among them, 47 (44%) patients had varices of varying sizes. Only 20 patients (8%) in the entire cohort were commenced on a beta blocker for primary prophylaxis and all these were commenced post screening endoscopy. During the follow-up period, 27 (10.8%) patients had their first episode of decompensation, and the decompensation free survival was 85% for beta-blocker group and 83.5% for the no beta blocker group (p=0.75). Patients who were commenced on a beta blocker had a longer mean (95% CI) time to decompensate 2.1 (0.3-3.8) years, compared to those who were not on beta blockers [mean (95% CI): 0.7 (01-1.4) years], (p=0.13).

Conclusion: Only a small proportion of patients meeting Baveno-VII criteria were appropriately commenced on beta blockers. Well compensated cirrhotic patients who were commenced on beta blocker as primary prophylaxis had a numerically better decompensation free survival and longer time to decompensate in a real-world setting, but these were not statistically significant. This is likely due to the small sample size and smaller number of decompensating events during the follow-up. A larger sample size is required for meaningful comparison between the two groups. We plan to extend this to a multicentre study to combine data from all tertiary referral centres in South Australia.

Reference

1. Villanueva C et al., Lancet 2019; 393: 1597-1608.

109

A rare case of isolated acute liver injury following mass envenomation by wasps

Hayneil Solanki, Tara Fox and Jerry Chin

Health New Zealand, Waikato, Hamilton, New Zealand

Introduction: Wasps are venomous insects belonging to the order hymenoptera, along with bees and hornets, with thousands of species in Australasia. They harbor the unique ability to sting a subject repeatedly during a single attack, exposing them to biogenic amines, enzymes and toxins. Wasp venom exposure (WVE) is a rare cause of acute liver injury (ALI), reported predominantly in the literature as a consequence of type 1 hypersensitivity, with cutaneous manifestations and multi-organ injury. Dose-dependent isolated hepatoxicity is a much rarer entity, which appears to be under-recognised. We present a case of isolated ALI following WVE with the view to increase clinician awareness of the condition and its possible prolonged course of recovery.

Case report: A previously fit and well 26-year-old Māori man presented with a five day history of jaundice following multiple wasp stings (>40 stings). Further history did not reveal identifiable precipitating factors for acute hepatitis. Aside from jaundice, there were no features of acute liver failure on clinical examination. Pertinent biochemistry included conjugated hyperbilirubinemia (peak 370 μmol/L) with hepatocellular injury (peak ALT 3970 U/L, AST 1620 U/L, ALP 196 U/L, GGT 173 U/L) as well as synthetic dysfunction (peak INR 1.7), with no evidence of other organ involvement. Comprehensive non-invasive liver screen was negative including viral/infective, autoimmune and metabolic causes. Magnetic Resonance Imaging excluded structural abnormalities. Liver biopsy demonstrated acute hepatitis and mild-moderate piecemeal necrosis. The patient was managed with supportive care including N-acetyl-cysteine infusion. Due to a rising bilirubin, empiric steroids were commenced at day 9 of admission and weaned over 40 days. Full recovery with complete normalisation of liver enzymes was seen at day 61 (Figure 1).

Discussion: Our case adds to the single existing case report of isolated ALI following WVE by Tsai et al in Taiwan. Two important differences are worth noting: first, a delayed reaction (WVE to jaundice time of >48 hours compared to 4 hours) and second, a prolonged time to resolution of jaundice, coagulopathy and liver enzymes (61 days vs. 4 days). We acknowledge the limitation of our case report in that there is lack of formal identification of the wasp involved.

111

Performance of hepatocellular carcinoma predictive scores in an Australian cohort with chronic hepatitis B infection

Thisuri Jayawardena¹, Luis Calzadilla Bertot^1,2, Joanne Bunney¹, Joanne Vallve¹, Zein Salim¹, Leon A Adams^1,2, Gary P Jeffrey^1,2 and Gerry MacQuillan^1,2

¹Hepatology Department and Liver Transplantation Service, Sir Charles Gairdner Hospital, Nedlands, Australia; ²University of Western Australia, Nedlands, Australia

Background and Aim: Current guidelines classify a large portion of patients with chronic hepatitis B (CHB) as high risk for developing hepatocellular carcinoma (HCC). These patients are recommended to undergo six-monthly liver ultrasound with or without serum alfa-feto-protein, placing a significant burden on radiology services, clinicians and patients. To optimise HCC risk stratification and rationalise screening, several predictive scores have been developed in international settings. These scores have not yet been validated in a large Australian cohort. This study assessed the performance of HCC predictive scores in a retrospective cohort of CHB patients attending a tertiary liver clinic in Western Australia.

Methods: Patients with CHB undergoing HCC surveillance from 1^st January 2017 to 30^th June 2023 were identified. Patients with prior HCC, liver transplant or lost to follow-up were excluded. The PAGE-B, modified PAGE-B, REACH-B, modified REACH-B and Hepascore were calculated at baseline, and patients followed for the development of HCC. Patients were classified into low risk (not requiring screening), intermediate and high risk (requiring screening) based on previously validated cut-offs. The primary outcome was the validity of each score (sensitivity, specificity and predictive values).

Results: 535 patients underwent HCC surveillance with a median follow up of 4.96 years. The median age was 49 years, 55% were male, 61% were of Asian ethnicity, 19% were of African ethnicity, 6.2% were Caucasian, 8.4% were cirrhotic and 47% received antivirals. Thirteen patients (2.4%) developed HCC during the study period (0.46 per 1000 person-years). Key results are reported in table 1. Data were available to calculate the time-dependent area under the curve at 3 years for the PAGE-B and modified PAGE-B scores which were 0.77 and 0.82 respectively. Both showed good overall accuracy (Integrated Brier Score 0.04 and 0.02 respectively) and discrimination (Gonen and Heller’s k-statistic 0.73 and 0.76 respectively). The cumulative incidence of HCC at 3 years for those classified as low, intermediate and high risk was 0%, 2.6% and 4.7% respectively for PAGE-B and 0.42%, 1% and 7.5% for modified PAGE-B.

114

To bleed or to clot? The challenging coagulopathy of liver disease

Joel Thio

Department of Gastroenterology and Hepatology, Logan Hospital, Brisbane, Australia

Introduction: Cirrhosis of the liver is complicated by its ability to cause both prothrombotic and antithrombotic changes. Portal vein thrombosis (PVT) is a common prothrombotic complication of liver cirrhosis which may be complete or partial. Alternatively, antithrombotic complications include spontaneous haematomas, variceal bleeding, and post-procedural bleeding. We present a case of concurrent portal vein thrombosis and spontaneous intracerebral haemorrhage in a cirrhotic patient, further illustrating this paradigm and challenges of management.

Discussion: This case highlights the difficulties of managing the complications of bleeding and hypercoagulability in patients with liver cirrhosis. In our patient, her intracerebral haemorrhage occurred spontaneously with no previous trauma, aneurysms, genetic risk factors, or anticoagulation. Development of PVT and SMV thrombus are known complications of liver disease, but there is growing suggestion that endoscopic variceal therapy could increase the risk of developing portal venous system thrombosis, presumably from increasing portal pressures, worsening venous stasis and hence thrombosis. The complications of bleeding and thrombosis in liver cirrhosis limit management options in such patients, and hence illustrates the challenging coagulopathy of liver disease.

121

Final results of the Australian prospective nucleos(t)ide analogue stop study: Long-term follow up identifies a higher incidence of functional cure in HBeAg-negative chronic hepatitis B

Simon Hume^1,2,3, Sam Hall¹, Gareth Burns⁴, Daniel Tassone¹, Paul Desmond^1,3, Dilip Ratnam⁵, William Sievert⁵, Miriam Tania Levy⁶, Rohit Sawhney⁷, Amanda Nicoll⁷, Simone Strasser⁸, Meng Ngu⁹, Zina Valaydon⁴, Marie Sinclair¹⁰, Christopher Meredith¹¹, Gail Matthews¹², Sara Vogrin³, Kumar Visvanathan^1,3, Jacinta Holmes^1,3 and Alexander Thompson^1,3

¹St Vincent's Hospital Melbourne, Fitzroy, Australia; ²Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia; ³University of Melbourne, Parkville, Australia; ⁴Western Health, Footscray, Australia; ⁵Monash Health, Clayton, Australia; ⁶Liverpool Hospital, Liverpool, Australia; ⁷Eastern Health, Box Hill, Australia; ⁸Royal Prince Alfred Hospital, Camperdown, Australia; ⁹Concord Hospital, Concord West, Australia; ¹⁰Austin Health, Heidelberg, Australia; ¹¹Bankstown-Lidcombe Hospital, Bankstown, Australia; ¹²St Vincent's Hospital Sydney, Darlinghurst, Australia

Background and Aim: Discontinuation of nucleos(t)ide analogue (NA) therapy has been associated with favourable outcomes including functional cure (HBsAg loss) amongst patients with chronic hepatitis B (CHB). A higher incidence of HBsAg loss has been reported in studies with longer follow up.

Methods: This is a prespecified analysis of the longer-term outcomes of participants enrolled in a prospective multicentre study of NA discontinuation (all patients were non-cirrhotic with HBeAg-negative CHB at enrolment; 85% were Asian). Following 96 weeks of follow up (outcomes previously reported), participants returned to standard of care and were reviewed 6 monthly and managed at the discretion of their treating practitioner. Key efficacy (including HBsAg loss) and safety outcomes [including ALT flare (ALT>2x upper limit of normal) and HCC (hepatocellular carcinoma)] were assessed.

Results: Data collection is ongoing with complete data expected by July 2024. Results are currently available for 81/110 participants with a median follow up of 6.8 years from NA discontinuation. Overall, treatment was recommenced for 67% of participants. 33% remained stable in the immune control phase. Beyond 96 weeks, an additional 7 patients achieved HBsAg loss to date, with a frequency of HBsAg loss of 7.8% at 4 years and 16.7% at 6 years (Figure 1). Early HBsAg loss (<96 weeks) was associated with very low end of treatment (EOT) HBsAg levels and was observed in the absence of ALT flares. In contrast, participants who achieved late HBsAg loss (>96 weeks) had higher EOT HBsAg levels (median 680 IU/mL vs 3.1 IU/mL, p<.05) and were more likely to have experienced a hepatitis flare (6/7 vs 0/7, p<0.05). Overall, 65 patients experienced an ALT flare. Of the seven patients who lost HBsAg beyond 96 weeks, four participants were re-treated with NA at the time of ALT flare. The median time from ALT flare to HBsAg loss was 155 weeks. No episodes of hepatic decompensation, liver transplant of death occurred. HCC was identified in three participants, all of whom were treated with curative intent and no patient has active disease at time of writing.

Conclusion: A higher incidence of functional cure was observed with longer follow up. Late HBsAg loss (>96 weeks) was associated with ALT flares suggesting that a subset of flares may be therapeutic.

127

Health and economic benefits of nucleoside analogue therapy in Australia: a cost-effectiveness analysis

Christopher Seaman^2,4, Yinzong Xiao^2,3, Jessica Howell^1,2,3 and Nick Scott^2,4

¹St Vincent's Hospital Melbourne, Fitzroy, Australia; ²Burnet Institute, Melbourne, Australia; ³University of Melbourne, Parkville, Australia; ⁴Monash University, Melbourne, Australia

Background and Aim: NUC therapy in the form of tenofovir disoproxil fumarate (TDF) and entecavir (ETV) stand as first-line treatments for hepatitis B in Australia. While impact of NUCs on reducing incidence of cirrhosis and liver cancer is well characterized through longitudinal studies, health and economic benefits within an Australian chronic hepatitis B (CHB) cohort are yet to be quantified.

Methods: Total mortality, survival time, and lifetime costs of CHB in Australia were compared for a natural history and a NUC treatment cohort using a Markov model. Rates of disease progression and treatment effectiveness were drawn from the literature and were reflective of individuals with treatment eligible CHB. Key costs of disease were considered disease management, hospitalization, liver transplants, and treatment; each estimated using an ingredients-based approach. Analysis took the health-providers perspective and used 2023 $AU discounted at 5% per annum. Monte Carlo sampling was used to quantify uncertainty (95% Credible Interval of 1000 model simulations).

Results: Without treatment, there were 443 (95%CrI: 182, 795) CHB-related deaths per 1000 people with treatment-eligible CHB, with average lifetime costs of $23,500 (95%CrI: 12,500, 67,900) per person. On NUCs, CHB-related deaths were reduced to 174 (95%CrI: 64, 245) with average lifetime costs of $32,800 (95%CrI: 21,100, 54,100) per person. Survival benefits from treatment were estimated at 5.8 (95%CrI: 1.2, 16.9) years, at an incremental cost of $1585 (95%CrI: -2702, 19551) per year of life gained. When total costs were adjusted for survival benefits, NUC therapy added a cost of $131 (95%CrI: -2091, 748) per person per year. Of this, $318 was incurred for treatment, but $188 averted in disease management and treatment costs.

130

Assessing the cost-effectiveness of a treat-all policy change for hepatitis B in six WHO regions

Christopher Seaman^2,4, Yinzong Xiao^2,3, Phillip Luong², Romesh Abeysuriya^2,4, Margaret Hellard^2,3,4, Jessica Howell^1,2,3 and Nick Scott^2,4

¹St Vincent's Hospital Melbourne, Fitzroy, Australia; ²Burnet Institute, Melbourne, Australia; ³University of Melbourne, Parkville, Australia; ⁴Monash University, Melbourne, Australia

Background and Aim: Globally, hepatitis B (HBV) treatment uptake is low. Adopting a “treat-all” approach for all people with HBV could remove barriers to treatment uptake and reduce transmission. This study evaluated the cost-effectiveness of a ‘treat-all’ approach for six WHO regions to achieve WHO 2030 HBV elimination targets, assuming no clinical benefits for individuals not meeting current treatment eligibility.

Methods: HBV epidemic models projected health and economic outcomes in each region for a baseline/status-quo and three scenarios: (1) treatment coverage among those currently ineligible (as per WHO 2015 guidelines) increased to levels among those currently eligible [“policy change”], (2) WHO elimination targets met by 2030 (90% diagnosis coverage and 80% treatment coverage among those eligible) [“elimination”], and (3) Elimination targets met plus expanding treatment to 80% of individuals diagnosed with CHB [“elimination + policy change”]. Incremental cost-effectiveness ratios (ICERs) were estimated for the policy change versus baseline scenarios, and the elimination + policy change versus elimination scenarios. Sensitivity analyses were conducted for treatment effectiveness, impact of treat-all policy change on diagnosis and/or treatment coverage.

Results: Over 2023-2050, the baseline scenario had 44.4 (42.0-49.2) million new HBV infections, 6.5 (6.4-6.6) million hepatocellular carcinoma (HCC) incident cases, 17.8 (16.8-18.3) million HBV attributable deaths and 314 (304-320) million HBV-related disability-adjusted life years (DALYs) globally. Compared with the baseline, scenarios 1, 2 and 3 had a 0.8%, 12.9%, and 42.8% reduction in new infections, a 0.6%, 23.5%, and 30.1% reduction in HCC incident cases, and a 0.3%, 38.0% and 39.5% reduction in HBV-attributable deaths, respectively. Scenario 1’s total impact was limited by low diagnosis coverage, with greater impact possible if a treat-all policy change led to both increased diagnosis and treatment coverage. The ICER of the policy change versus baseline scenarios ranged from US$650 per DALY averted in the WHO South-East Asia Region (SEAR) to US$4129 per DALY averted in the WHO European Region (EUR). The ICER for elimination + policy change versus elimination was higher than for policy change versus baseline, suggesting that for settings where elimination care cascade targets are already achieved, the clinical benefits for people currently ineligible will be an important consideration for cost-effectiveness.

Conclusion: The public health benefits of a ‘treat-all’ HBV policy could lead to important reductions in new HBV infections, HCC cases and deaths, but impact is potentially limited by low diagnosis coverage. A ‘treat-all’ policy is increasingly cost-effective where it improves the HBV care cascade.

136

Interim analysis of a single-centre, prospective, randomised trial comparing a multidisciplinary, multimodal, home based intervention with standard of care in adult patients post hospitalisation for hepatic decompensation

Natalie Ngu^1,2, Thomas Worland¹, Patricia Anderson^1,2, Edward Saxby¹, Stephanie Yung¹, Joshua Abasszade¹, Eliza Flanagan^1,2, Bowen Xia¹, Jo Hunter¹, Benjamin Rogers^1,2, William Sievert^1,2, Adam Irving², Sally Bell^1,2 and Suong Le^1,2

¹Monash Health, Melbourne, Australia; ²Monash University, Melbourne, Australia

Background and Aim: Hepatic decompensation frequently necessitates hospitalisation, with an estimated Australian admission rate rise from 8.5/10,000 in 2008 to 11.21/10,000 in 2016¹ and annual cost increase by 78% from 2012 to 2018² at our health service. Trials of chronic disease management (CDM) programs have had variable impact on re-admission rates^3,4. LivR Well is a 28-day, multidisciplinary, multimodal, home based intervention targeting enhanced liver recovery immediately post hospitalisation.

Methods: Recruitment for a randomised controlled study at an Australian, non-liver transplant health service was undertaken from February 2022 to March 2024. Patients with acute hepatic decompensation were recruited from inpatient admissions and randomised 1:1 to LivR Well, or standard care. The intervention group received a hepatology consultation weekly and allied health consultations as required from physiotherapist, dietitian, pharmacist, social worker, and/or addiction medicine specialist, coordinated by a hepatology clinical nurse consultant. The control group received a hepatology consultation within 4 weeks of discharge and then at clinician discretion. Chronic liver disease questionnaire (CLDQ) and EuroQoL-5 Dimension instruments were performed at baseline, week 6 and week 12. The primary outcome was 30-day re-admission. Secondary outcomes were 28-day mortality, health-related quality of life (HRQoL), admission and ambulatory care costs, and change in MELD score.

Results: 104 patients were enrolled and randomized, of which 73 (n=32 control, n=41 intervention) have 6 month follow up data and are included in this interim analysis. There was no difference in baseline characteristics between groups. Overall, the median age was 56 years (IQR: 47-65), 71% were male, and the most frequent aetiologies of liver disease were alcohol (74%) followed by MAFLD (18%). Median baseline Child-Pugh and model for end-stage liver disease-Sodium (MELD-Na) scores were 10 (IQR: 9-11) and 19 (IQR: 16-24) respectively. Ten patients in the intervention group dropped out, of which 6 did not start the program, and 2 in the control arm dropped out following randomization. There was no difference in re-admission between Intervention and Control groups at 30 days (Incidence Rate Ratio (IRR) 1.60, 95% CI 0.60-4.52, p=0.31), 90 days (IRR 1.36, 95% CI 0.62-3.17, p=0.42) or 6 months (IRR 1.16, 95% CI 0.57-2.40, 0.67) with readmission-free survival shown in Figure 1 (p=0.772). Twenty-eight-day mortality was low overall (n=0 vs. n=2) with 11 deaths in total at 6 months (n=6 vs. n=5). There was no difference in MELD-Na at baseline or at Day 28 however the score in all groups improved by a median 24% (IQR: 3-50). Both groups had a low baseline overall CLDQ score (3.48±1.51 vs. 3.91±1.25, p=0.26) reflecting poor HRQoL, compared to week 6 (4.32±1.25 vs. 5.11±1.06, p=0.11). The mean intervention cost was $5353±2142. Patients in both LivR Well and control groups received regular albumin infusions (n=1 vs. n=3), elective large volume abdominal paracentesis (n=12 vs. n=8), and elective endoscopy (n=13 vs. n=14). Despite the intervention group being scheduled for weekly appointments for the first 4 weeks, there was no difference at 6 months in mean frequency of clinic attendance (7.1±4.4 vs. 6.3±3.1, p=0.62) and total clinic costs using Medicare Benefits Scheme costs was similar ($982±537 vs. $888±380, p=0.62). The sum total costs for the 73 patients over 6 months including re-admissions, albumin infusions, elective abdominal paracentesis, elective endoscopy, and clinic appointments was $2 453 008 vs. $2 472 797.

Conclusion: Patients with decompensated liver disease had low short-term mortality, and improvements in liver disease severity and QoL regardless of treatment group. Control arm patients accessed enhanced supportive care, which may have contributed to lack of significant difference in outcomes between groups. Further evaluation of this cohort over a longer follow up or the inclusion of another control group more closely simulating standard care will provide insight into any components of this CDM program contributing additional benefit and which can be replicated in other centres.

References

1. Powell, EE et al. Increasing Hospitalization Rates for Cirrhosis: Overrepresentation of Disadvantaged Australians. EClinicalMedicine. 2019; 11: 44-53.

2. Lovett, GC et al. Healthcare utilisation and costing for decompensated chronic liver disease hospitalisations at a Victorian network. Intern Med J. 2023; 53(9): 1581-7.

3. Wigg, A et al. A randomized multicenter trial of a chronic disease management intervention for decompensated cirrhosis. The Australian Liver Failure (ALFIE) trial. Hepatology. 2024. DOI: https://doi.org/10.1097/HEP.0000000000000862

4. Tapper, E et al. A quality improvement initiative reduces 30-day rate of readmission for patients with cirrhosis. Clin Gastroenterol Hepatol. 2016; 14(5): 753-759.

144

Passive transfer of anti-HBc after IVIG – the TAPAS study (Transmission of Anti-HBc Passively After IVIG Study)

Isabella Commins¹, Evangelia Dendrinos¹, Denis Shi^1,2, Barbara Demediuk¹, Tim Papaluca¹, Thai Hong¹, Jessica Howell^1,2, Marno Ryan^1,2, David Iser¹, Jacinta Holmes^1,2 and Alexander Thompson^1,2

¹St Vincent's Hospital Melbourne, Melbourne, Australia; ²The University of Melbourne, Melbourne, Australia

Background and Aim: Passive transfusion of anti-HBc antibodies after treatment with IVIG has been reported. Differentiating IVIG-related passive transfusion of anti-HBc from past infection with hepatitis B virus (HBV) can be difficult, but is an important distinction for patients who subsequently need B cell depleting therapy. The frequency of passive transfusion of anti-HBc after IVIG treatment, and the rate of persistence is not known. We performed a retrospective analysis of the frequency of anti-HBc positivity detected after IVIG therapy, and evaluated the testing rate for baseline HBV serology prior to IVIG therapy.

Methods: A retrospective, single centre study was carried out at a tertiary referral hospital. All patients who received IVIG from January 2023 – December 2023 were identified using the electronic medical record. We recorded clinical demographics, baseline and follow-up HBV serology, and the incidence of the need for B cell depleting therapy post IVIG.

Results: 153 patients were identified who received at least 1 dose of IVIG. The median (IQR) age was 65 years (50 – 73), 50% were male. 57% were being treated for a neurological and 23% for a rheumatological condition. 93 patients (61%) were receiving concurrent immunosuppression, most commonly with systemic corticosteroids (74/93, 80%). Only 73 (48%) had HBV serology recorded prior to IVIG therapy. Patients who had HBV serology were more likely to be receiving concurrent immunosuppression (p <0.001). All 73 patients tested were negative for HBsAg. 9/73 patients (12%) had a positive baseline anti-HBc. 17 patients (11%) were found to be anti-HBc positive after IVIG therapy. Of these, 7 were known to be positive prior to IVIG therapy, 4 had no baseline serology, and 6 patients seroconverted from anti-HBc negative pre-IVIG, to anti-HBc positive post-IVIG, consistent with passive anti-HBc transfer. 7/153 patients (4.6%) progressed to B cell depleting therapy after IVIG. 4/7 had HBV serology at baseline; 2 patients were anti-HBc positive pre-IVIG consistent with past HBV infection; 2 patients seroconverted to anti-HBc positive post IVIG (suspected passive transfer). 3/7 had no baseline HBV serology. 6/7 patients were started on entecavir prophylaxis against HBV reactivation. 1 patient was not started on prophylaxis as they were deemed to have had likely passive transfer of anti-HBc.

145

Global epidemiology, natural history, maternal-to-child transmission, and treatment of pregnant women with hepatitis C: a systematic review and meta-analysis of 311,905,738 women

Joo Wei Ethan Quek¹, Jing Hong Loo², En Qi Lim³, Ambrose Hon-Lam Chung³, Abu Bakar Bin Othman³, Jarell Jie-Rae Tan¹, Scott Barnett⁴, Mindie H Nguyen^4,5 and Yu Jun Wong^1,2,3,6

¹Yong Loo Lin School of Medicine, National University of Singapore, Singapore; ²Department of Gastroenterology & Hepatology, Changi General Hospital, Singapore; ³Duke-NUS Medical School, Singapore; ⁴Division of Gastroenterology & Hepatology, Stanford University Medical Center, Palo Alto, United States of America; ⁵Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, United States of America; ⁶Division of Gastroenterology & Hepatology, University of Alberta, Edmonton, Canada

Introduction: Pregnant women with hepatitis C virus (HCV) infection represent a special population in which treatment access remains limited despite its increasing prevalence. This study aimed to determine the prevalence, maternal-to-child transmission (MTCT), maternal and fetal complication rates, and direct acting antivirals (DAA) treatment outcomes of chronic HCV in pregnant women.

Method: We performed a systematic review and meta-analysis to identify studies reporting the prevalence, MTCT, and complications of HCV infection in pregnant women.

Results: From a total of 311,905,738 pregnant women from 333 studies, the pooled global seroprevalence of HCV in pregnant women was 2.6% (95%CI: 2.0-3.2), which increased in patients with intravenous drug abuse. Seroprevalence varied by geographical region, with the highest found in the Eastern Mediterranean (4.7%, 95%CI: 3.4-6.2), followed by Americas (3.4%, 95%CI: 1.7-5.6), Africa (2.4%, 95%CI: 1.9-2.9), Southeast Asia (1.6%, 95%CI: 0.8-2.7), and Western Pacific region (1.6%, 95%CI: 0.4-3.5) and Europe (1.5%, 95%CI: 0.8-2.4). Most patients were diagnosed through universal screening (75%). Viremic prevalence of HCV in pregnant women was 1.3% (95%CI: 0.7-2.2). The pooled MTCT rate was 9.0% (95%CI: 6.6-11.7), which was higher with HIV co-infection (OR: 2.29, 95%CI: 1.56-3.35) but not influenced by the mode of delivery or breastfeeding. Pregnant women with HCV infection had more maternal complications, including intrahepatic cholestasis (OR: 12.97, 95%CI: 4.01–41.99), preterm delivery (OR: 1.62, 95%CI: 1.45–1.81), and antepartum hemorrhage (OR: 1.39, 95%CI: 1.15–1.68). Neonates from HCV mothers had significantly higher odds of being small for gestational age (OR: 1.74, 95%CI: 1.30–2.31). The pooled rate of sustained virologic response (SVR12) among the 74 women treated with DAA during pregnancy was 100%. Common adverse events included nausea or vomiting (17.6%), headaches (10.8%), and fatigue (9.5%), with no serious maternal adverse events requiring treatment cessation or any fetal adverse events reported.

Conclusion: HCV prevalence in pregnant women varies by geographic region and patient population, while MTCT occurs in almost one in ten viremic mothers. Pregnant women with HCV had a significantly higher risk of both maternal and neonatal complications. Early data suggests that DAA are safe and efficacious in pregnant women with HCV infection. Majority of HCV in pregnant women was diagnosed through universal screening, suggesting that HCV screening should be offered to all pregnant women. The diagnosis of HCV in pregnant women is vital for linking care for HCV to address the major unmet need of eradicating HCV in mothers and infants.

147

Epidemiology and outcomes of primary biliary cholangitis patients undergoing liver transplantation: An Australian 37-year cohort study

Yael Celermajer¹, Akalya Mahendran², David Bowen¹, Rachael Jacob¹, Madeleine Gill¹, Talal Valliani¹, Simone Strasser¹, Geoffrey McCaughan¹ and Ken Liu¹

¹Royal Prince Alfred Hospital, Sydney, Australia; ²Bankstown Hospital, Sydney, Australia

Background and Aim: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease which can progress to decompensated cirrhosis and liver transplantation (LT) despite advances in medical treatment. The epidemiology and outcomes of PBC patients undergoing LT in Australia is not well-described and this forms the aim of our study.

Methods: We retrospectively studied consecutive adults with PBC who underwent deceased-donor LT between 1987-2023. Donor and recipient data at time of LT and recipient outcomes were collected from a prospective LT database. The primary outcome of interest was graft survival (time to retransplant or death). Secondary outcomes were the development of recurrent PBC (rPBC) as defined by liver biopsy or documentation by treating clinician and biopsy-proven allograft rejection.

Results: During the study period, 1960 patients received LT of which 95 (5%) were PBC patients: 88% female, median age 53 years (IQR 47-61), 85% anti-mitochondrial antibody positive. Patients were diagnosed with PBC a median of 10 years (IQR 5-16) before LT. Most patients (91%) were taking ursodeoxycholic acid (UDCA) leading up to LT with the minority taking second-line therapies (2% obeticholic acid, 3% fenofibrate). The indication for LT was decompensated cirrhosis in 94% (66% with ascites, 36% with encephalopathy, median model for end-stage [MELD) liver disease score 21 [IQR 16-24]) and HCC in 6%. The most common induction immunosuppression regimen was corticosteroids, tacrolimus and mycophenolate (47%) which was also the most common maintenance regimen (46%). Most (77%) patients restarted UDCA at a median of 20 days (IQR 4-106) post-LT. Of these, 14% were started prophylactically to prevent rPBC, 32% to treat rPBC and 55% for deranged liver function tests without a definitive diagnosis of rPBC. No patients received second-line PBC therapy post-LT. After a median follow-up of 9.3 years (IQR 4.7-20.6), there were 46 deaths (50%) and 2 retransplants (2%). Based on Kaplan Meier analysis, the estimated median graft survival was 20.6 years (95% confidence interval [CI] 14.0-27.0) with 1-year, 5-year and 10-year graft survivals of 94%, 84% and 68%, respectively. rPBC was diagnosed in 29% at a median of 4.2 years post-LT. Of these, 56% were biopsy proven while the remainder were based on clinician assessment. On multivariable analysis, the only independent predictor of rPBC was increased MELD score at time of LT (hazard ratio [HR] 1.14 per point increase, 95% CI 1.01-1.29, P=0.035). rPBC did not impact on long-term graft survival (Log-rank P=0.227). Over half (58%) of patients developed biopsy-proven allograft rejection during the follow-up period. Biopsy-proven rejection was associated with worse graft survival (HR 3.07 for death or retransplant, 95% CI 1.03-9.13, P=0.044).

158

Impact of addiction medicine consultation on mortality in patients with alcohol-related liver disease: A retrospective cohort study

Tsz Hong Yiu¹, Aisha Khalid^1,2, Hans Mautong^2,3, Jennifer Andraos¹, Emily Matejin¹, Kerrie Curin¹, Nicola McGuinn¹ and Zina Valaydon^1,4

¹Western Health, Melbourne, Australia; ²Department of PGME (Post grade medical education), Harvard Medical School, Boston, United States; ³Department of Medicine, John H. Stroger Jr. Hospital of Cook County, Chicago, United States; ⁴Department of Medicine, University of Melbourne, Melbourne, Australia

Background and Aim: Alcohol-related liver disease (ALD) carries significant morbidity, and alcohol abstinence is crucial for improving clinical outcomes. Addiction medicine (AM) services play a pivotal role in providing psychosocial therapy and medications to ensure long-term abstinence. Western Health (WH) is a large tertiary hospital serving a catchment area of 1.2 million people in socioeconomically disadvantaged areas of Melbourne, characterized by a high density of immigrants from non-English speaking backgrounds (NESB), low health literacy, and high rates of alcohol misuse. Given the significant burden of ALD, our study aims to examine the impact of inpatient AM consultations on mortality in patients with ALD.

Methods: We retrospectively collected data from the electronic medical records of all patients admitted with ALD to WH from January to December 2021. We documented demographics, presenting complaints, and the involvement of AM during the admission. Univariate and multivariable logistic regression analyses were performed to assess predictors of liver-related mortality, defined as death resulting from liver disease complications up to a 2-year follow-up.

Results: Our study included 169 admissions of ALD patients, with a mean age of 57 years (SD 15); 70% (n=118) were male. Among these patients, 75% (n=127) were still consuming alcohol and 96% (n=162) had cirrhosis. Of the cirrhotic patients, 21% (n=34) were classified as Child-Pugh (CP) A, 43% (n=69) as CP-B, and 36% (n=59) as CP-C. 78.4% (n=127) cirrhotic patients were previously decompensated and had not yet recompensated. Common presenting complaints included symptomatic ascites in 26% (n=44), falls and functional decline in 21% (n=35), and upper gastrointestinal bleeding in 20% (n=35). Inpatient AM team was consulted in only 52% of cases (n=88). The overall 2-year mortality was 20% (n=18) for those where the AM team was consulted, compared to 49% (n=40) for those without (Table 1). Univariate logistic regression showed a statistically significant reduction in 2-year mortality with inpatient AM input (OR 0.35, 95% CI: 0.16-0.73, p=0.006). A multivariate logistic regression model indicated that the mortality reduction associated with inpatient AM input was independent of gender, age, and CP status (OR 0.30, 95% CI: 0.12–0.77, p=0.012).

Conclusion: Our study demonstrated that AM input is associated with reduced mortality in ALD patients. Currently, only half of the ALD patients were consulted by AM, possibly due to patient non-engagement and counselling difficulties arising from language barriers. Future research should focus on identifying the underlying barriers to AM involvement, and efforts should be directed towards increasing access and streamlining referrals to AM for ALD patients.

161

Anti-HBs immune complex levels: A novel biomarker of hepatitis flare in patients with HBeAg-negative chronic hepatitis B who stop nucleos(t)ide analogue therapy

Simon Hume^1,2,3, Sam Hall¹, Gareth Burns⁴, Kathy Jackson², Peter Revill^2,3, Margaret Littlejohn^2,3, Darren Wong⁵, Kaylene Cheng^1,3, Sara Vogrin³, Jacinta Holmes^1,3, Kumar Visvanathan^1,3, Alexander Thompson^1,3 and Nadia Warner^2,3

¹St Vincent's Hospital Melbourne, Fitzroy, Australia; ²Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia; ³University of Melbourne, Parkville, Australia; ⁴Western Health, Footscray, Australia; ⁵Austin Health, Heidelberg, Australia

Background and Aim: The saturation of HBsAg by the formation of anti-HBs immune complexes (HBsAg-IC) has made it challenging to study the humoral immune response in chronic hepatitis B (CHB). We have previously optimised an immune complex assay for quantifying anti-HBs in the presence of HBsAg. We have previously observed that on treatment ALT flares leading to HBsAg loss are associated with an increase in HBsAg-IC. The role of HBsAg-IC in the pathophysiology of hepatitis flare warrants further study.

Methods: HBsAg-IC levels were evaluated amongst 34 patients previously enrolled in a prospective study of nucleos(t)ide analogue (NA) discontinuation with 96 weeks of follow-up (all patients were non-cirrhotic with HBeAg-negative CHB). Patients with available stored sera were selected (21 cases with ALT > 10 x ULN, 5 cases with ALT 2-10 x ULN and 8 controls with no ALT flare). HBsAg-IC was isolated using an established polyethylene glycol precipitation method with quantification subsequently performed using the Roche Elecsys system. End-of-treatment (EOT; at NA cessation) and longitudinal HBsAg-IC levels were used to predict clinical outcomes including hepatitis flare (ALT >5xULN with HBV DNA >2000 IU/mL) and major flare (ALT >10xULN with HBV DNA >2000 IU/mL).

Results: At EOT, the median age was 54 years, 62% were male, 79% were Asian and the median EOT HBsAg titre was 547 IU/mL. HBsAg-IC level was detectable at EOT in 33/34 participants with a median level of 9.78 IU/mL. A high EOT HBsAg-IC (≥39 IU/mL or 75^th centile) was associated with a reduced risk of major flare (22% vs 76%, p=.01) and a trend towards a lower risk of hepatitis flare (44% vs 83%, p=.05). Amongst participants who experienced a flare, peak flare was associated with an increase in HBsAg-IC levels (Figure 1) and occurred at the time of peak ALT in 92% of patients. No significant change in HBsAg-IC levels were observed over time in the patients without flare.

Conclusion: This is the first study to demonstrate that higher EOT HBsAg-IC levels are associated with a lower risk of flare amongst individuals who stop NA therapy and therefore may be a marker of immune control. Amongst those who experienced a hepatitis flare off-treatment, a rapid rise in HBsAg-IC level was observed at time of peak ALT. This suggests that the humoral immune system may play an important role in the pathophysiology of hepatitis flare.

165

Interactions between sarcopenia, frailty and resting energy expenditure in patients with cirrhosis and portal hypertension

Rachael Jacob^1,2, Joanne Craik¹, Aviv Pudipeddi^2,5, Laura Park⁶, Grace Aw⁷, Natalie Ngu¹, Helen Vidot¹, Talal Valliani¹, Madeleine Gill^1,2, David Bowen^1,2,3, Simone Strasser^1,2, Geoffrey McCaughan^1,2,4 and Ken Liu^1,2,4

¹AW Morrow Gastroenterology & Liver Centre, Royal Prince Alfred Hospital, Sydney, Australia; ²Faculty of Medicine and Health, University of Sydney, Sydney, Australia; ³Liver Immunology Program, Centenary Institute, Sydney, Australia; ⁴Liver Injury and Cancer Program, Centenary Institute, Sydney, Australia; ⁵Concord Repatriation General Hospital, Sydney, Australia; ⁶Alfred Health, Melbourne, Australia; ⁷Department of Medical Imaging, Royal Brisbane and Women’s Hospital, Brisbane, Australia

Background and Aim: Sarcopenia and frailty are prevalent and independently prognostic in cirrhosis. Few studies have evaluated both entities together to ascertain their interaction and phenotypic differences. Their relationship with resting energy expenditure (REE) is also unclear. Thus, we examined sarcopenia, frailty and REE in a cohort of patients with cirrhosis and portal hypertension.

Methods: We retrospectively studied consecutive adult patients with cirrhosis and portal hypertension who were prospectively recruited to undergo sarcopenia (Transversal Psoas Muscle Thickness [TPMT]/height), frailty (Fried Frailty Index [FFI]) and nutritional assessments between 2015-2018. Sarcopenia and frailty were defined as TPMT/height ≤16.8mm/m and FFI ≥3/5 respectively. For analysis, patients were categorised into four groups based on their sarcopenia and frailty status: not frail and not sarcopenic (NFNS), not frail but sarcopenic (NFS), frail but not sarcopenic (FNS), and frail and sarcopenic (FS). The primary outcome was transplant-free survival (TFS).

Results: During the study period, 97 patients were recruited for assessment (71% male, median age 57 [IQR 52-63]). Median Child-Pugh score was B9 (IQR 7-10) and median model for end-stage liver disease (MELD) scores was 16 (IQR 11-20). Frailty assessment was completed in 96 patients (99%), CT sarcopenia measurement in 90 (93%) and indirect calorimetry in 63 (65%). Over half the cohort (59/97, 61%) had all three measurements performed. By FFI, 40% (38/96) were classified as frail, while 26% (23/90) were classified as sarcopenic by TPMT/height. Patients were further categorised into four subgroups depending on the presence of sarcopenia and frailty: NFNS (52%); FNS (23%); FS (16%); and NFS (9%). The median predicted (by Harris-Benedict equation) and measured (by indirect calorimetry) REE were 1637 (IQR 1440-1799) and 1695 (IQR 1459-1955) kcal/day respectively. The majority of patients were normometabolic (48/63, 76%), while 13 (21%) were hypermetabolic and two (3%) were hypometabolic. There was a modest but significant correlation between TPMT/height and FFI (Spearman rho = -0.266, p=0.016). Patients with sarcopenia or frailty alone were phenotypically similar, except those with sarcopenia had a lower median body mass index (BMI) (23 vs 28 kg/m², p=0.032) and were more likely to be hypermetabolic (60% vs 0%, p=0.017). After a median follow up of 5.7 years (IQR 2.2-7.6), 50 (51%) of patients underwent liver transplant (LT) and 35 (36%) of patients died. The median overall TFS was 7.2 months (95% CI 4.8-9.6). By Kaplan-Meier analysis, median TFS was significantly lower in patients who were sarcopenic (3.6 vs 8.3 months; p=<0.001) or frail (4.5 vs 13.4 months; p=0.032) (Figure 1a & 1b). When comparing all subgroups, sarcopenia and frailty had a cumulative impact, with the lowest median TFS seen in the FS (1.8 months, 95% CI 1.4-2.1) compared to the NFNS, NFS and FNS groups (log rank p=0.001) (Figure 1c). Independent predictors of death or LT were sarcopenia (lower TPMT/height) (aHR = 0.930 per mm/m increase, 95% CI 0.868-0.996, p=0.037), presence of hepatic encephalopathy (aHR = 2.051, 95% CI 1.211-3.474, p=0.008), and higher MELD score (aHR = 1.114 per point increase, 95% CI 1.073-1.156, p<0.001).

167

Mortality in a large gastroenterology and liver service – the impact of alcohol-related liver disease in the younger cohort

Angela Nguyen^1,4, Mrinal Unuth¹ and Georgia Crowley^1,2,3

¹Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, Australia; ²The University of New South Wales, Sydney, Australia; ³The Ingham Institute for Applied Medical Research, Liverpool, Australia; ⁴School of Medicine, Western Sydney University, Campbelltown, Australia

Background and Aim: Cirrhosis is the 11^th leading cause of death worldwide and liver cancer the 16^th, both of which affect a younger cohort.¹ Yet, 71% of healthcare expenses in Australia reportedly went to those over 65 years despite representing 14% of the population. ² We sought to characterise those patients who died under the Gastroenterology and Liver Service (GLS) in Liverpool Hospital, Australia in an effort to identify modifiable factors according to age.

Methods: We conducted a retrospective analysis of admitted patients under the GLS who died during their admission (January 2021 to January 2023). Data was collected from electronic medical records, including demographics, outpatient reports and cause of death.

Results: There were 111 mortalities, median age 70 (IQR: 59-80), and 62% were male. Median length of stay until death was 8 days (IQR: 4-20). Eleven (10%) were from a nursing home. Forty (36%) were non-English speaking. Forty-six (41%) had a Charlson Comorbidity Index of ≥7 at admission. Liver disease accounted for 46% (n = 51) of deaths including 16 (14%) with hepatocellular carcinoma (HCC) and 38 (34%) with decompensated cirrhosis (alcohol-related cirrhosis (AC) in 28 (74%), metabolic dysfunction associated steatotic liver disease (MASLD) in 5 (13%), viral hepatitis in 7 (18%) and cardiac cirrhosis 1 (3%)). Non-liver-related causes were non-cirrhotic gastrointestinal bleeding in 13, malignancy (non-HCC) in 21, pancreato-biliary benign disease 4, and many miscellaneous in 32. Cirrhosis was newly diagnosed (during admission or in the preceding two months) in 40% of those with AC vs 11% for those with non-AC (p = 0.02). Only 5 of 37 with AC were known to the Drug and Alcohol service. Of those with known cirrhosis prior to admission, only 21% had any clinical service engagement within the previous three months. Those under 70 years more frequently died due to decompensated cirrhosis (56% vs 11%, p < 0.00001) (Fig. 1). They were more commonly male (72% vs 52%, p = 0.03) and AC was the cause of 75% of these.

References

1. Asrani, SK, Devarbhavi, H, Eaton, J, Kamath, PS. Burden of liver diseases in the world. J Hepatol. 2019; 70(1): 151-71.

2. Harris, A, Sharma, A. Estimating the future health and aged care expenditure in Australia with changes in morbidity. PLoS One. 2018; 13(8):e0201697.

174

Hepatic steatosis in young adults is associated with altered gut microbiology

Yasmina Tashkent^1,2,3, Jocelyn Choo^1,2, Alyson Richard², Jenny Wang⁴, Luis Calzadilla Bertot⁴, Steven Taylor^1,2, Kerry Ivey⁵, Oyekoya Ayonrinde⁴, Brendan Adler⁸, Trevor Mori⁴, Lawrence Beilin⁴, John Olynyk⁷, Alan Wigg^1,3, Kate Muller^1,3, Geraint Rogers^1,2 and Leon A Adams^4,6

¹Flinders University, Adelaide, Australia; ²South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia; ³Flinders Medical Centre, Adelaide, Australia; ⁴University of Western Australia, Perth, Australia; ⁵Harvard University, Cambridge, United States of America; ⁶Sir Charles Gairdner Hospital, Perth, Australia; ⁷Curtin University, Perth, Australia; ⁸Envision Medical Imaging, Perth, Australia

Background and Aim: Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide, and is most commonly related to metabolic dysfunction–associated steatotic liver disease. The gut microbiome has been linked to SLD pathogenesis in children, adolescents and older adults with steatosis. Our aim was to identify changes in the gut microbiome of young adults that may contribute to steatosis development.

Methods: 1082 participants of the Raine Study birth cohort underwent cross-sectional assessment at age 27 years. Hepatic steatosis was quantified using a validated magnetic resonance imaging (MRI) volumetric liver fat fraction (VLFF) equation (HepaFat) with a >3.55% cut-off used to identify SLD. Participants were divided into three groups for analysis (no steatosis: VLFF ≤3.55%, mild-moderate steatosis: VLFF 3.56 – 13.55% and severe steatosis: VLFF >13.55%). Gut microbiome profiling was performed using 16S rRNA V4 amplicon sequencing of stool samples.

Results: Of 588 participants for whom complete data was available, 488 (83%) had no steatosis, 76 (12.9%) had mild-moderate and 24 (4.1%) had severe steatosis. Compared to no steatosis, severe steatosis was associated with significantly lower microbiota alpha diversity (observed features [p=0.015], Pielou evenness [p=0.001], and Shannon entropy [p=0.002]) (Figure 1). Faecal microbiota composition differed significantly between no steatosis and mild-moderate (p=0.008) and severe steatosis groups (p=0.002) using unrestricted permutational multivariate analysis of variance (PERMANOVA). The severe steatosis group gut microbiota were significantly more dispersed (higher within-group variation) than those in the no steatosis group (p (perm)<0.001). Compared to no steatosis, the severe steatosis group exhibited a significantly lower relative abundance of bacteria associated with short-chain fatty acid (SCFA) production and significantly higher levels of the proinflammatory bacterial taxa Lachnoclostridium and Ruminococcus gnavus group (False Discovery Rate corrected p<0.05).

179

Case report: Ascitic fluid polymerase chain reaction enables early diagnosis of HSV hepatitis - a novel concept

Daniel Oliver¹ and Alex Prudence²

¹John Hunter Hospital, Newcastle, Australia; ²Universtiy of NSW, Sydney, Australia

Introduction: Herpes Simplex Virus (HSV) hepatitis is a rare but aggressive cause of hepatitis with a rapid progression to fulminant disease. It accounts for 2% of virally induced acute liver failure (ALF) with liver biopsy being the gold standard for diagnosis. HSV hepatitis’ rarity, lack of unique clinical features and often absent characteristic lesions, results in a late diagnosis that is often fatal even with treatment.

Case report: We describe a case of ALF due to HSV hepatitis in a 20-year-old female who initially presented with abdominal pain due a flare of Crohn’s Disease. The patient was immunosuppressed with azathioprine 75mg PO and hydrocortisone 100mg QID IV with recent use of Prednisone 50mg PO as an outpatient. On the 5^th day of admission, the patient developed a fever of 39.4C accompanied by a steep rise in liver function tests (LFTs) with AST of 2016 U/L and ALT 1714 U/L from AST 20U/L and ALT 12 U/L at admission. New thrombocytopaenia was noted with platelets 33 x10⁹/μL. Azathioprine was ceased, a non-invasive liver screening panel sent, and abdominal ultrasound completed that revealed a smooth liver with no lesions, no biliary dilation, and the presence of moderate ascites. On day 6, the bilirubin increased to 27 μmol/L with INR 2.6, the development of encephalopathy with an AST of 4829U/L and ALT 3504U/L. The patient was admitted to the intensive care unit. A high index of suspicion for systemic HSV evolved following the discovery of characteristic genital lesions and treatment with IV acyclovir commenced. Abdominal paracentesis was performed, excluding SBP. Ascitic fluid was sent for viral PCR and returned a positive result for HSV 2 DNA. Subsequent liver biopsy showed viral inclusions with immunohistochemistry positive for HSV2. The PCR from genital lesions was positive for HSV2, confirming a diagnosis of systemic HSV2 infection. The patient was treated with 3 weeks of IV acyclovir with normalisation of liver function tests. This was followed by oral valaciclovir 500mg daily for 3 months for suppression whilst on weaning doses of prednisone awaiting biologic commencement for management of Crohn’s Disease.

Conclusion: This is the only case in the literature in which ascitic fluid PCR has aided an early diagnosis of HSV hepatitis. As characteristic lesions are not always present, ascitic fluid PCR may prove a useful diagnostic test in cases of acute liver failure to facilitate early diagnosis and treatment, whilst awaiting definitive liver biopsy.

180

Unhealthy plant-based diets are associated with hepatic steatosis in young adults

Yasmina Tashkent^1,2,3, Therese O’Sullivan⁴, Dujinthan Jayabalan^5,6, Sophie Miller^1,2, Luis Calzadilla Bertot⁵, Steven Taylor^1,2, Brendan Adler⁷, Trevor Mori⁵, Lawrence Beilin⁵, Oyekoya Ayonrinde⁵, John Olynyk⁸, Richard Woodman¹, Jocelyn Choo^1,2, Geraint Rogers^1,2, Kate Muller^1,3, Alan Wigg^1,3 and Leon A Adams^5,6

¹Flinders University, Adelaide, Australia; ²South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia; ³Flinders Medical Centre, Adelaide, Australia; ⁴Edith Cowan University, Perth, Australia; ⁵University of Western Australia, Perth, Australia; ⁶Sir Charles Gairdner Hospital, Perth, Australia; ⁷Envision Medical Imaging, Perth, Australia; ⁸Curtin University, Perth, Australia

Background and Aim: Dietary intake is a key driver of metabolic dysfunction-associated steatotic liver disease. Plant-based diets have been recommended for cardio-metabolic health, however, unhealthy plant-based diets (uPD) may have opposing impacts on hepatic steatosis compared with healthy plant-based diets (hPD). We therefore aimed to quantify the relationship between consumption of a healthy and unhealthy plant-based dietary pattern and the presence of hepatic steatosis in young adults.

Methods: 887 participants of the population-based Raine Study underwent assessment at age 27 years, including a clinical questionnaire, anthropometrics and dietary assessment using a Food Frequency Questionnaire (FFQ). Hepatic steatosis was quantified using a validated magnetic resonance imaging volumetric liver fat fraction equation (HepaFat) and a previously established cut-off >3.55% indicating the presence of hepatic steatosis. Data from the FFQ was used to create two primary measures: 1) hPD index (positive scores given to healthy plant food groups and reverse scores to animal and unhealthy plant food groups) and 2) uPD index (positive scores given to unhealthy plant food groups and reverse scores to animal and healthy plant food groups). Individual healthy and unhealthy plant food groups were also analysed.

Results: Of 887 participants (mean age 27 years, 463 [52%] female), 142 (16%) had hepatic steatosis. Participants with hepatic steatosis had a significantly higher uPD index and lower hPD index than those without (Table 1). The positive association between steatosis and the uPD index remained after adjustment for waist circumference, sex and alcohol intake (Odds Ratio (OR) 1.04, [Confidence Interval (CI) 1.01-1.07; P=0.013], whereas the association with the hPD index was not significant after adjustment (OR 0.993, CI 0.962-1.03; P=0.661). Steatosis was also associated with a significantly lower consumption of vegetables, legumes, nuts, fish/seafood and tea/coffee and higher consumption of fruit juice and animal-based processed food (P<0.001) (Table 1).

Conclusion: A diet with more unhealthy plant-based foods is associated with hepatic steatosis in young adults, whereas diets rich in healthy plant-based foods may be protective potentially through a higher consumption of vegetables, legumes, nuts and tea/coffee.

184

Effect of pro-dopamine oral docarpamine on ascites: an open-label phase 2a study to assess safety and effectiveness in patients with refractory ascites due to liver cirrhosis

Edmund Tse², Nick Kontorinis³, Martin Weltman⁴, Alicia Braund⁵, Rohit Sawhney⁶, Ann Tunstall⁷, Ibrahim Mian⁷ and James O'Beirne¹

¹Sunshine Coast University Hospital, Birtinya, Australia; ²Royal Adelaide Hospital/University of Adelaide, Adelaide, Australia; ³Royal Perth Hospital, Perth, Australia; ⁴Nepean Hospital, Kingswood, Australia; ⁵Gold Coast University Hospital, Southport, Australia; ⁶Department of Gastroenterology, Eastern Health/Eastern Health Clinical School, Monash University, Melbourne, Australia; ⁷Martin Pharmaceuticals, New York, USA

Background: Docarpamine (DCP) is an orally available dopamine prodrug approved in Japan to transition patients with circulatory failure from IV dopamine to oral therapy. In several small studies, DCP was shown to improve refractory ascites in patients with liver cirrhosis. In this study, we aim to re-evaluate the safety and effectiveness of DCP.

Methods: Patients with liver cirrhosis with refractory ascites dependent on periodic large volume paracentesis (LVP) and MELD-Na ≤ 25 received open-label oral DCP 750mg TID (low) or 1500mg TID (high) for up to 90 days. Primary outcome measures were safety and tolerability. Clinical outcomes included total volume of ascites drained and frequency of LVP pre-treatment (Pre-tx) compared to on-treatment (On-tx) and post-treatment (Post-tx) periods.

Results: Eight subjects received the low dose, and 8 the high dose. All but one had alcohol-associated liver disease. Ten subjects, 5 at each dose level, experienced a total of 18 SAEs, 17 of which were hospitalizations due to complications of ascites, expected in this condition and considered unrelated to study drug. One event with concurrent tachycardia and vomiting occurred after the initial 1500mg dose, was thought related to DCP, and resulted in study drug discontinuation. Overall, a total of 113 AEs were recorded in 16 subjects. The most common events were vomiting (7), nausea (4), and abdominal pain (4), none of which led to discontinuation of study drug except for the one event listed above. Welch’s t-test was used to evaluate efficacy of the pooled doses. Comparing On-tx to Pre-tx, the total volume of removed ascites decreased by 14% [p=0.47 (n=13)] and the total number of LVPs decreased by 13% [p=0.33 (n=13)]. Comparing Post-tx to Pre-tx, the volume decreased by 53% [p=0.01 (n=9)] and frequency by 44% [p=0.01 (n=10)]. This pattern was seen in both doses. The Mixed Model for Repeated Measures yielded similar trends in reduction of volume [On-tx 9% (p=0.3); Post-tx 27% (p=0.02)] and frequency [On-tx 11% (p=0.2); Post-tx 33% (p=0.01)].

Conclusions: Oral DCP was safe and well-tolerated in patients with liver cirrhosis with refractory ascites. Given the statistically significant reduction of ascites volume and LVP frequency in the Post-tx period, it is postulated that treatment with DCP induces neurohumoral changes leading to a delayed effect. Considering the unmet medical need for the treatment of refractory ascites, further studies are warranted to evaluate the efficacy of DCP.

188

A systematic review on the efficacy and safety of faecal microbiome transplantation in severe alcoholic hepatitis

Evance Pakuwal¹, Jin Lin Tan^1,2, Amanda Page³, Andrea Stringer⁴ and Mohamed Asif Chinnaratha^1,2

¹Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia; ²Department of Gastroenterology/Hepatology, Lyell McEwin Hospital, Haydown Road, Elizabeth Vale, Australia; ³School of Biomedicine, University of Adelaide, Adelaide, Australia; ⁴Department of Clinical and Health Sciences, University of South Australia, Adelaide, Australia

Background and Aims: Severe alcoholic hepatitis (sAH), as defined by Maddrey’s DF ≥32, has a high short-term mortality. Prednisolone is currently the standard of care (SOC) in these patients albeit with increased risk of infections. Faecal Microbiota Transplantation (FMT) has shown some benefits in small studies in this cohort of patients. This systematic review aims to provide updated evidence on the comparative efficacy and safety of FMT in sAH patients.

Methods: Electronic reference databases (PubMed, EMBASE, and Cochrane Central) were searched from inception till 4^th December 2023 for studies comparing FMT with the standard of care in sAH patients. The primary aim is to compare the short-term survival. The secondary aims include comparing: (i) medium- and long-term survival (ii) adverse events and (iii) changes in relative abundance (RA) of pathogenic species and gut microbiome communities. The modified Newcastle Ottawa Scale (mNOS) was used for study quality assessment.

Results: Seven studies with 387 patients (184 in the FMT group and 203 in the SOC group) met the eligibility criteria and were included in this review^1-7. Of these, there were two prospective non-randomized studies, two randomized controlled trials and three retrospective studies. All studies were of fair quality when assessed using the mNOS scale. Four studies reported on the 28-day and 90-day survival rates, two studies reported the 6-months and one study reported 12-month survival rates. The FMT group had a higher 28-day- survival rate (75-100%) compared to SOC group (48-80%). Additionally, 90-day, 6-month, 1-year survival rates were higher in the FMT group compared to the SOC group (Table 1). A meta-analysis could not be performed due to the presence of significant heterogeneity among the included studies. No treatment-related mortality or serious adverse events were reported among the included studies. For the microbial outcomes, the RA of pathogenic species, such as Klebsiella pneumonia, was reduced with time in the FMT group compared to the standard-of-care group⁶. The RA of beneficial bacteria such as Bifidobacterium and Bacteroides was observed in FMT-treated patients at 3 months post-treatment. The Bifidobacterium was significantly higher at 6 months in FMT patients⁷.

Conclusion: Based on the limited available evidence, FMT is a safe and efficacious treatment option in sAH patients. It improves the short, medium-, and long-term survival in sAH patients, with no major adverse events. FMT also aids in gut microbial recovery. A larger RCT with adequate sample size is required to confirm these findings.

References

1. Philips, et al., Indian Journal of Gastroenterology, 2018; 37(3): 215–225.

2. Sharma, et al., Hepatology Int., 2022; 16: 433–446.

3. Pande, et al., Hepatol Int., 2023 Feb; 17(1): 249-261.

4. Kumar, et al., Journal of Clinical and Experimental Hepatol., 2022; 12(S2): S49.

5. Philips, et al., Gastroenterology Report., 2022a; 1–10.

6. Philips, et al., Clinical Gastroenterology and Hepatol., 2017; 15: 600–602.

7. Philips, et al., Journal of Clinical and Experimental Hepatol., 2022b; 12(4): 1124–1132.

189

Good and evil: Mediterranean diet vs ultra-processed food intake and prevalent metabolic dysfunction-associated steatotic liver disease in older Australians

Daniel Clayton-chubb^1,2, Jessica Fitzpatrick^1,2, William Kemp^1,2, John Lubel^1,2, Isabella Commins¹, Ammar Majeed^1,2, Alex Hodge², Robyn Woods², Alice Owen², John McNeil² and Stuart Roberts^1,2

¹Alfred Health, Melbourne, Australia; ²Monash University, Melbourne, Australia

Background and Aim: Lifestyle and dietary factors are commonly implicated in the development and perpetuation of metabolic dysfunction-associated steatotic liver disease (MASLD). Guidelines often recommend a Mediterranean diet (MedDiet) pattern of eating for individuals with MASLD. There is also an increasing focus on Ultra-Processed Foods (UPF) and their association with overall and cardiometabolic health. However, their importance in older adults is understudied. As such, we aimed to identify whether dietary habits consistent with MedDiet or UPF intake were associated with decreasing or increasing prevalence of MASLD respectively.

Methods: This study is a post hoc analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) randomized trial and the ASPREE Longitudinal Study of Older Persons (ALSOP) sub-study, with 12,581 respondents. MASLD was defined using standard criteria with Fatty Liver Index (FLI) ≥ 60 identifying hepatic steatosis. A UPF Diet Score (UPFQ) and MedDiet score (MDS) were developed based on self-reported eating patterns for the preceding 12 months via a 54-item FFQ. Higher scores indicate greater exposure to these dietary factors. UPFQ and MDS were analysed in quartiles. Associations were drawn using Poisson regression with robust variance. Primary comparisons were between MASLD (FLI ≥ 60) and no-MASLD (FLI < 30) (FLI 30-60 is indeterminate).

Results: We included the 6,882 participants (median 76.8 [IQR 74.6 – 80.1] years) who adequately answered a semi-quantitative FFQ during ALSOP and were classifiable by the FLI. Of these 6,882, 29.3% (2,016) were classified as MASLD, 36.1% (2,486) as no-MASLD, and 34.6% (2,380) as indeterminate. Population UPFQ scores were median 6.0 (range 0.3 – 14.0), and MDS were median 11.4 (range 3.3 – 16.6). On univariate analysis, there was a strong association between the highest compared to lowest quartile of UPF intake and MASLD with a RR 1.27 [95% CI 1.16 – 1.40], and a strong inverse association between the highest quartile of MDS compared to the lowest (RR 0.66 [95% CI 0.60 – 0.72]). Results remained significant when adjusting for multiple relevant co-factors (Table 1), and were similar when comparing MASLD to FLI < 60. When examining only the highest quartile of MDS, increasing UPF intake was associated with increasing risk of MASLD on unadjusted analysis (RR 1.07 [95% CI 1.03 – 1.12]), but not when fully adjusted (aRR 1.03 [95% CI 0.99 – 1.07]).

Conclusion: In initially relatively healthy older adults, self-reported higher intake of UPFs was associated with increased prevalence of MASLD while higher adherence to a MedDiet was associated with a lower prevalence of MASLD. These data may support recommendations to increase MedDiet adherence and reduce UPF intake in MASLD.

196

Compensated advanced chronic liver disease management in primary care: good quality with the right model

Alvin Lee^1,2, Jeyamani Ramachandran^1,2, Kate Muller^1,2, Rachel Wundke¹, Kylie Bragg¹ and Alan Wigg^1,2

¹Flinders Medical Centre, Adelaide, Australia; ²Flinders University, Adelaide, Australia

Background and Aim: Despite an increasing global emphasis on the adoption of care pathways for chronic liver disease (CLD) in the primary care setting, CLD has not yet been incorporated within the spectrum of chronic diseases that are managed by general practitioners (GPs) in Australia. Therefore, at a tertiary hospital in South Australia, a de-centralised model of care (MOC) was developed in consultation with GPs to transition patients with stable compensated advanced CLD (cACLD) back to their GPs. The aim of this study was hence to examine the quality of care received by patients with cACLD following transition to this new MOC.

Methods: We conducted a retrospective analysis of all adult patients at our centre who transitioned to this new MOC with a greater than 12-month follow-up period. Quality outcome measures that were assessed included adherence to surveillance for hepatocellular carcinoma (HCC) and hepatic osteodystrophy, as well as appropriate titration of beta-blocker prophylaxis for patients with clinically significant portal hypertension (CSPH). The transition to primary care was supported by GP protocols outlining care requirements, including triggers for referral back to the tertiary care system. Additionally, hepatology nurses provided ongoing annual reviews with vibration-controlled transient elastography as well.

Results: 172 patients with cACLD were included in this study, with a median follow-up period of 15.1 months (IQR 13.9-17.3). The average age was 66 years (SD 10.7) with a majority being male (59.9%), and the predominant aetiologies for their cACLD included alcohol-related liver disease (41.9%), metabolic-associated fatty liver disease (32.6%), and Hepatitis C virus (22.7%). Adherence to 6-monthly abdominal ultrasounds and serum Alpha-Fetoprotein testing was 79.7% and 79.1% respectively. In addition, adherence to 2-yearly Bone Mineral Density scans and serum Vitamin D testing was 74.4% and 75.6% respectively. Of the 79 patients with CSPH, 65 (82.3%) were being appropriately managed on Carvedilol by their GP. Of the five patients who met triggers for referral back to a hepatology unit, all were appropriately referred back by their GP. Significantly, no patients experienced any preventable presentations or admissions to hospital from their underlying cirrhosis. However, one patient suffered a serious adverse event in primary care related to a missed diagnosis of HCC, which was due to non-adherence to ultrasound surveillance.

197

A retrospective cohort study of perioperative analgesic practices in liver transplant recipients

Zhenxi Wang², Alvin Lee^1,2, Adam Badenoch¹, Rohan Wheaton¹, John Chen^1,2, Libby John¹, Kate Muller^1,2, Jeyamani Ramachandran^1,2 and Alan Wigg^1,2

¹Flinders Medical Centre, Adelaide, Australia; ²Flinders University, Adelaide, Australia

Background and Aims: Perioperative pain management strategies for liver transplantation (LT) are evolving. Challenges of analgesia in this setting include rapidly changing liver function and increased risks of opiate addiction in patients with prior drug and alcohol misuse. Additionally, there is a lack of consensus and well-defined protocols to guide optimal analgesic regimens in this context. The aims of this study were to: (1) describe current analgesic regimens employed at our LT centre and (2) describe the effectiveness and safety of current analgesic regimens.

Methods: A retrospective cohort study design was employed to describe the analgesic regimens administered to patients who underwent LT between 1st January 2022 and 31st December 2022 through review of their electronic medical records.

Results: 20 liver transplant recipients were included in the study. The median (IQR) Model for End-Stage Liver Disease (MELD) score at LT was 19 [15-29]. The median (IQR) length of stay was 16 days [12.3-25.3]. Alcohol related cirrhosis was the most common (40%) indication for LT. Opioids were used in all patients for postoperative pain management, with a high mean daily morphine milligram equivalent (MME) of 28.1 (SD 32.8). Fentanyl was the primary MME source, with all patients receiving parenteral Fentanyl on their first day in the Intensive Care Unit (ICU), and 15% continuing after discharge from ICU. Patient controlled opiate analgesia (PCA) was only used in a minority (40%) of patients. Tramadol, an opiate with a smaller side effect profile, was used in only 15% of patients. The median (IQR) time to first receive oral analgesics and Paracetamol was 3 days [2-4] and 6 days [5-7], respectively. Only 20% of patients had regular Paracetamol prescribed as part of their initial analgesic regimen. More than half (55%) of patients were discharged with prescriptions for Oxycodone despite cessation of this medication prior to discharge. A higher MME was found to significantly correlate with the incidence of postoperative nausea, vomiting, and ileus. The mean pain scores reported by LT recipients was 2.63 (SD 0.90) (see Figure). Postoperative chronic pain was reported by 10% of patients at 3 months follow-up. Subgroup analysis did not identify a difference in MME between patients with a history of prior alcohol misuse and those with no past history (MME consumption 30.3 versus 30.7, p value= 0.968).

198

Ascites liver training initiative: Quality improvement study to increase rates of timely diagnostic paracentesis

Lucy Vaux, Kate Vaughan, Rohit Gupta and James O'Beirne

Sunshine Coast University Hospital, Birtinya, Australia

Background and Aim: Ascites is the pathological accumulation of fluid in the peritoneal cavity. Cirrhosis is the predominant aetiology of ascites in the Western world. Spontaneous bacterial peritonitis (SBP) is the bacterial infection of ascites that occurs without an apparent source. The prevalence of SBP among patients admitted to the hospital is estimated to be around 10%. Performing a diagnostic paracentesis is the standard of care for all patients admitted to the hospital with cirrhosis and ascites to rule out SBP. Diagnostic paracentesis is a low-risk procedure and can safely be performed in patients with advanced cirrhosis. However, inpatient diagnostic paracentesis is frequently not performed or delayed. This was evident in a local audit which found that only 16% of the patients admitted with ascites had a diagnostic paracentesis within 12 hours of admission. The primary factors that influenced this outcome were the knowledge gaps among junior clinicians on the indications for paracentesis and their lack of procedural experience. We developed a quality improvement (QI) study targeting barriers to timely diagnostic paracentesis. Our aim is to improve the rates of timely diagnostic paracentesis for inpatients with cirrhosis and ascites.

Methods: The study includes a comprehensive paracentesis training program for junior doctors. This involves a didactic 20min lecture outlying indications for diagnostic paracentesis, diagnosis and treatment of SBP. This is followed by a 30-minute practical session using a paracentesis training model and point of care ultrasound. The knowledge of each attendant is assessed pre-session and post-session, via 10 randomly selected questions from a total of 20 (via Excel Randomization Equation).

Results: 47 junior doctors have been involved in the training program over three months. The pre-session results demonstrated 64.7% correctly answered questions. The post session results demonstrated 86.8% correctly answered questions. The overall improvement to knowledge was identified in 70.2% (33/47) of participants. Statistical analysis using the signed Wilcoxon rank test demonstrated a higher post-session median score of 4 compared to the pre-session score of 3 (p < 0.001).

Conclusion: We have demonstrated that a practical training session provides improved knowledge to participating junior doctors. The next step will be to audit rates and timing of diagnostic paracentesis post 6 months of regular education sessions. This will hopefully identify a practical and simply method to improve diagnostic paracentesis rates and improve patient outcomes.

Table 1:

200

Optimising timely detection of very early-stage hepatocellular carcinoma in Australia: A multi-centre, combined retrospective and prospective cohort study of hepatocellular carcinoma diagnosis in Melbourne, Victoria

Kiran Gopinath Iyer¹, Joan Ericka Flores¹, Tom Sutherland¹, Ashu Jhamb¹, Marno Ryan¹, Brett Knowles¹, Adrian Fox¹, Ammar Majeed², Stuart Roberts², William Kemp², Marie Sinclair³, Amanda Nicoll⁴, Rohit Sawhney⁴, Stephen Bloom⁴, Gauri Mishra⁵, Zina Valaydon⁶, Alexander Thompson¹ and Jessica Howell¹

¹St Vincent's Hospital Melbourne, Fitzroy, Australia; ²The Alfred Hospital, Melbourne, Australia; ³Austin Hospital, Heidelburg, Australia; ⁴Eastern Health, Box Hill, Australia; ⁵Monash Health, Clayton, Australia; ⁶Western Health, Footscray, Australia

Background and Aim: Hepatocellular carcinoma (HCC) has a high mortality if diagnosed at late stage. Enrolment in surveillance with 6-monthly liver ultrasounds remains vital to detect HCC early when potentially curable. The best outcomes are reported in people with Barcelona Clinic Liver Cancer (BCLC) stage 0 disease, or very early-stage HCC. However, there are limited Australian data describing prevalence of very early stage HCC and impact on clinical outcomes. This study aimed to describe the proportion of incident BCLC stage 0 and BCLC stage A disease in an Australian cohort, identifying demographic and clinical characteristics associated with BCLC 0 stage HCC and impact on first treatment modality and survival.

Methods: We performed a multi-centre retrospective and prospective cohort study of all incident HCC cases diagnosed between January 1^st, 2018 and October 31^st, 2022 across 6 tertiary centres in Victoria. HCC cases were identified using clinical HCC databases, cross-referenced with HCC multidisciplinary team (MDT) meeting discussions and electronic medical records. Primary outcome was the proportion of HCC cases with BCLC stage 0 versus BCLC stage A disease; secondary outcomes were HCC surveillance uptake, first treatment modality and survival in early stage HCC (BCLC 0 or A). Enrolment in surveillance was defined as at least one documented appointment for a surveillance liver ultrasound within 12 months of HCC diagnosis. Bi-variable analysis was performed using chi square test and Mantel-Haenztel odds ratios were calculated; multivariable logistic regression and Cox proportional hazards models were built using stepwise elimination and likelihood ratio testing to identify variables associated with diagnosis of BCLC stage 0 disease and survival.

Results: 569 of 1203 (47%) incident HCC cases diagnosed across 6 centres were early BCLC stage 0 or A HCC. Within this cohort, 133 cases (23.4%) were diagnosed at BCLC stage 0, and 436 cases (76.6%) were diagnosed at BCLC stage A. Most (80%) were male with cirrhosis (80%), with a median age of 66 years. Most HCC cases were due to hepatitis C (35%), alcohol-related liver disease (32%), and metabolic-associated steatotic liver disease (32%). On bivariable analysis, compared to BCLC stage A disease, BCLC stage 0 HCC was associated with younger age (63 years (IQR 56, 71)) vs 66 years (IQR 60, 74; p=0.007), compensated vs decompensated cirrhosis (OR 3.3, 95% CI 1.7-6.4, p<0.001) and enrolment in HCC surveillance (OR 2.5, 95% CI 1.6-3.8, p<0.001). Patients with stage 0 HCC were also more likely to undergo surveillance scans in a tertiary hospital compared to a community radiology service (OR 2.7 (95% CI 1.7-4.4, p<0.001)). However, on multivariate analysis, enrolment in HCC surveillance remained the only significant factor associated with BCLC stage 0 vs BCLC stage A HCC (aOR 2.6, 95%CI 1.7-4.0, p<0.001). First treatment allocation varied between BCLC stage 0 and A HCC; people with BCLC stage 0 more likely to receive laparoscopic or percutaneous microwave ablation (52% compared with 27%, p<0.001), whereas people with BCLC stage A HCC were more likely to receive surgical resection (31% vs 20%, p=0.009). 77% (102/133) patients with BCLC stage 0 HCC were allocated curative first line treatment compared to 59% (257/436) patients with BCLC stage A HCC (p<0.0001). Downstaging with first-line TACE was also more common among those with BCLC stage A compared with stage 0 HCC (30% versus 13%; p<0.001). Overall, 150 people died during follow up; 22 (17%) BCLC stage 0 and 128 (29%) stage A. People with BCLC stage 0 had significantly longer survival from diagnosis compared to BCLC A stage HCC, adjusted for age and Child-Pugh status (aHR 1.64, 95% CI 1.03-2.61, p=0.034). Median time from diagnosis to death was 24.8 months (IQR 13.9, 32.3) in BCLC stage 0 HCC compared to 16.1 months (IQR 7.7, 30.5; p=0.07) in those with BCLC stage A HCC.

Conclusions: Diagnosis of incident BCLC stage 0 HCC is increased by timely liver cancer surveillance. People with BCLC stage 0 HCC are more likely to receive curative ablative therapy rather than surgical resection and have longer post-HCC survival compared to patients with BCLC stage A HCC. These findings highlight the need to invest in strategies to increase timely HCC surveillance uptake in Australia.

216

Experience of transjugular intrahepatic portosystemic shunt insertion for patients from metropolitan and rural areas

Darragh Egan, Adam Doyle, Justin Chin, Nick Kontorinis, Jee Kong, Wendy Cheng and Tim Mitchell

Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Australia

Background and Aim: Transjugular intrahepatic portosystemic shunt (TIPS) is an important option for managing complications of portal hypertension. We aimed to explore the demographics, indications, outcomes and complications of patients undergoing TIPS in our center from rural areas compared with those from the metropolitan area.

Methods: We undertook a retrospective analysis of all patients who had undergone TIPS in our department between May 2021 and January 2024. This data was collected with a plan to build an ongoing database. Data included patient demographics, TIPS indication, MELD score, Child-Pugh score, immediate (during hospitalisation) and late (following discharge) complications, incidence of hepatic encephalopathy, requirement for TIPS revision or closure and death. Unpaired t-test and Fisher’s exact test were used for statistical analysis.

Results: We identified 23 patients who underwent TIPS in our center between May 2021 and January 2024. The mean age of the cohort was 53.8years-old and 60.8% were male. Seven patients (30.4%) lived in a rural area. A higher proportion of rural patients were Indigenous Australian. Post-TIPS hepatic encephalopathy (HE) was common and generally responded to medical management, however two patients required TIPS narrowing for refractory HE. Overall, TIPS was well tolerated and provided excellent control of symptoms with no difference in outcomes between metropolitan and rural patients (Table 1).

Conclusion: TIPS is an effective treatment for patients suffering from complications of portal hypertension. Our center performed 23 TIPS across a 32-month period, including in 7 patients from rural WA where access to specialist healthcare is limited. These patients had good outcomes and TIPS reduced the need for them to travel to Perth for repeated interventions. These patients were predominantly followed up via telehealth, in consultation with their local healthcare team.

217

Stereotactic ablative body radiotherapy versus ablation for the treatment of early-stage hepatocellular carcinoma

Darragh Egan¹, Fadak Mohammadi², Lauren Andersson^1,3, William Ormiston⁴, Jonathan Tibballs⁴, Shaun Samuelson⁴, Matthys Van Wyk⁴, Matthew Clifford⁴, Luis Calzadilla Bertot^1,5, Hien Le⁶, Colin Tang⁷, Michael Wallace^1,5 and Alan Wigg^1,8

¹Department of Hepatology, Sir Charles Gairdner Hospital, Nedlands, Australia; ²Hepatology and Liver Transplantation Medicine Unit, Flinders Medical Centre, Bedford Park, Australia; ³Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; ⁴Department of Interventional Radiology, Sir Charles Gairdner Hospital, Nedlands, Australia; ⁵Medical School, University of Western Australia, Nedlands, Australia; ⁶Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia; ⁷Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia; ⁸College of Medicine and Public Health, Flinders University of South Australia, Adelaide, Australia

Background and Aim: Stereotactic ablative body radiotherapy (SABR) shows promise as a curative therapy for early-stage hepatocellular carcinoma (HCC) by delivering high dose, targeted radiation. Its use is limited by a lack of high-quality comparative data with current standard of care treatments. The aim of this study was therefore to assess the efficacy of SABR compared to percutaneous ablation (PA) in a large Australian cohort, with the primary outcome of local recurrence.

Methods: This was a retrospective cohort study from two quaternary referral centers from May 2012 to February 2024 of 276 patients (369 tumours treated) who underwent SABR or PA (MWA and RFA) with a minimum 1-year follow-up. Cox proportional hazard regression analysis was performed per tumour treated. Adverse events (AEs) were recorded according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 5.

Results: A total of 235 episodes of SABR and 134 episodes of PA in 276 patients were included. The cohorts had a similar median age (65 vs 63) and similar percentage of male patients (80% vs 82%). Most common aetiology for both cohorts was hepatitis C followed by alcohol associated liver disease. Clinical characteristics that differed significantly between SABR and PA groups included ECOG score of 0 (70% vs 95%; p<0.0001), prior HCC treatment (71% vs 46%; p<0.0001), tumours >3cm (22% vs 5%; p<0.0001) The mean dose of radiation in the SABR group was 43.9 Gy delivered in a mean of 3.8 fractions. Local recurrence rates in the SABR cohort were 4.6% (95 % CI 2.5-8.4%), 6.0% (CI 3.2-10%) and 6.0% (95% CI 3.2-10%) at 1, 2 and 3 years respectively. Local recurrence rates in the ablation cohort were 11% (95% CI 6.8-18%), 18% (95 %CI 12-27%) and 21% (95 %CI 14.8-31%) at 1, 2 and 3 years respectively (p<0.001) (Figure). After adjustment for age, sex, MELD, previous HCC treatment, tumour size, AFP and BCLC stage, the SABR cohort had an 85% reduced risk of recurrence compared to the PA cohort (HR 0.15; 95 % CI 0.06-0.37, p<0.01). For progression events outside the radiation field there was a similar rate for SABR and PA 50.2% versus 46.3% respectively (p=0.466). Rate of treatment related adverse events (AE) was identical in both groups (43%). There was only one Grade 3 AE, an hepatic abscess 4 months post SABR.

Conclusion: This is the largest study of early HCC treated with SABR in Australia. SABR demonstrated excellent local tumour control compared to PA, and a low rate of serious AEs. Our observational study is further justification for ongoing randomized controlled trials investigating primary treatment with SABR vs standard of care for early-stage HCC.

219

The accelerated impact of alcohol-associated hepatitis on healthcare utilisation during the COVID-19 pandemic: An Australian multicentre analysis.

Leya Nedumannil¹, Steven Cheema¹, Simon Hume^1,2, Thomas Goodwin³, Robert Little³, Timothy Phan², Thang Dao^2,9, Ronald Ma⁴, Daryl Jones^5,7, Stephen Warrillow⁵, Jessica Howell^2,8,9,10, Ammar Majeed³, William Kemp³, Alexander Thompson², Stuart Roberts^3,11, Josephine Grace^1,6, Karl Vaz^1,3, Darren Wong^1,6 and Matthew Choy^1,6

¹Department of Gastroenterology and Hepatology, Austin Health, Melbourne, Australia; ²Department of Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, Australia; ³Department of Gastroenterology, Alfred Hospital, Melbourne, Australia; ⁴Clinical Costing, Austin Health, Melbourne, Australia; ⁵Department of Intensive Care, Austin Health, Melbourne, Australia; ⁶Department of Medicine, Austin Academic Centre, University of Melbourne, Melbourne, Australia; ⁷Department of Critical Care, University of Melbourne, Melbourne, Australia; ⁸Department of Disease Elimination, Burnet Institute, Melbourne, Australia; ⁹Department of Medicine, University of Melbourne, Melbourne, Australia; ¹⁰Department of Epidemiology and Disease Prevention, Monash University, Melbourne, Australia; ¹¹Central Clinical School, Monash University, Melbourne, Australia

Background and Aim: Alcohol-associated hepatitis (AAH) causes significant morbidity, mortality, and healthcare expenditure. Increased alcohol consumption during the SARS-CoV-2 (COVID-19) pandemic was observed internationally. This study aimed to assess temporal associations between the COVID-19 pandemic and AAH admission frequency and outcomes.

Methods: A retrospective cohort study was conducted analysing AAH admissions and outcomes in three large Australian tertiary academic hospitals between 1st March 2020-31^st March 2021 (“COVID-19 cohort”) compared with a “historical cohort” (1^st January 2016 – 29^th February 2020). Inclusion criteria was inpatients aged > 18 years fulfilling the National Institute of Alcohol Abuse and Alcoholism (NIAAA) diagnostic criteria for AAH. The primary endpoint was monthly AAH admission rate according to COVID-19 timepoint. Secondary outcomes included change in AAH severity, interventions, healthcare costs, and mortality.

Results: In total, 301 eligible AAH admissions were identified (n=104 in the COVID-19 cohort, n=197 in the historic cohort). The COVID-19 cohort had a higher median AAH monthly admission rate [8 (IQR 6,9) vs 3 (IQR 3,5), p<0.0001], with a 76% increase compared to the historic cohort on multivariate Poisson analysis. There was a larger proportion requiring intensive care unit (ICU) admission in the COVID-19 cohort [26% (n=27) vs 12% (n=24), p=0.002] despite similar severity of liver disease as reflected by baseline MELD-Na score [20 (IQR 15-25.5) vs 19 (IQR 14-25), p=0.24]. Median total health cost per day of admission was higher in the COVID-19 cohort [$2,330 (IQR 1,507, 3,313) vs $1,870 (IQR 1,593, 2,372), p=0.024], as were median monthly costs [$90,912 (IQR 43,853, 243,469) vs $42,983 (IQR 18,231, 71,410), p=0.03]. Ninety-day mortality was 14%. No patients were diagnosed with COVID-19.

Conclusion: In this multicentre analysis, AAH admission frequency, ICU requirement and healthcare costs increased significantly during the COVID-19 pandemic. These results underscore the escalating impact of alcohol consumption on healthcare utilisation, and hence provide the impetus to better integrate preventative strategies into routine AAH management to mitigate alcohol-related admissions in the future. It also prompts consideration of the broader impact of health policy decisions, such as lockdowns, on lifestyle behaviours.

220

The power of knowledge: Evaluating disease knowledge and awareness in patients with liver cirrhosis

Leya Nedumannil¹, Catherine Yu¹, Mustafa Mohamedrashed¹, Diana Lewis¹ and Siddharth Sood^1,2

¹The Northern Hospital, Epping, Australia; ²The University of Melbourne, Parkville, Australia

Background and Aim: Patient understanding is an essential component of chronic disease management. In patients with cirrhosis, inadequate disease comprehension has been associated with increased healthcare utilisation. We aimed to evaluate knowledge regarding chronic liver disease and its complications amongst patients with cirrhosis.

Methods: Inpatients with cirrhosis admitted to the Gastroenterology Unit were offered a knowledge questionnaire previously validated in this cohort (1), to voluntarily complete on discharge. The questionnaire comprised 14 questions, each scored out of 1, which covered ascites management (out of-5), variceal bleeding management (out of-3), hepatic encephalopathy (HE) management (out of-3), hepatocellular carcinoma surveillance (out of-1), and lifestyle measures (out of 2). The primary outcome was total knowledge score, and secondary outcome was breakdown scores for each knowledge category.

Results: 61 patients with cirrhosis [median age 61 years (IQR 46.5-70.5), 34% (n=21) female] were identified between 1^st March 2023 and 1^st March 2024. Median Child Pugh score was 8 (IQR 7-9) and MELD-Na score 19 (IQR 14-23). 73.8% (n=45) patients had ascites, 20% (n=1) had > Grade 2 hepatic encephalopathy (HE), and 5% (n=3) presented with variceal bleeding. 66% (n=40) of patients invited completed the questionnaire, achieving a median total score of 8.5 out of 14 (IQR 7-10). Median scores per topic demonstrated poor knowledge particularly with respect to HE (Table 1). A presentation with > Grade 2 HE did not improve knowledge regarding HE compared to those without [median score 1 out of 3 (IQR 0-2) for both groups, p=0.76]. Despite poor knowledge scores regarding HE, 57% (n=35) patients were prescribed lactulose with/without rifaximin. Of the 21 patients who did not complete the questionnaire, 38% (n=8) were from a non-English-speaking background, compared to 25% (n=10) of those who completed it (p=0.29).

Conclusion: Patients with cirrhosis generally possess a suboptimal depth of knowledge about liver health. Our patients, regardless of encephalopathy status on admission to hospital, exhibited notable shortcomings in their understanding about HE. Despite daily clinician assessment for hepatic asterixis, and prescription of lactulose with/without rifaximin for more than half our patients, the deficiency in patient knowledge about HE is noteworthy and reflects a failure in adequate clinician-patient communication. Unlike ascites, which is more conspicuous and easier for patients to comprehend, HE is often insidious and requires active education before it develops. These findings highlight the need to enhance clinician-led education for patients with cirrhosis and ideally, their next of kin, prior to hospital discharge.

Reference

1. Ramachandran, J, Woodman, RJ, Muller, KR, Wundke, R, McCormick, R, Kaambwa, B, Wigg, AJ. Validation of Knowledge Questionnaire for Patients With Liver Cirrhosis. Clin Gastroenterol Hepatol. 2020 Jul; 18(8): 1867-1873.

249

Assessing the quality of non-targeted liver biopsies: A portal towards improved reporting

Leya Nedumannil¹, Natasha Walker¹, Eda Gungormez¹, Mustafa Mohamedrashed¹, Siddharth Sood^1,2 and Diana Lewis¹

¹The Northern Hospital, Epping, Australia; ²The University of Melbourne, Parkville, Australia

Background and Aim: Liver biopsy plays a crucial role in the diagnosis and prognostication of several liver pathologies. Although a relatively invasive procedure, advancements in technology and reporting have improved the diagnostic value of liver biopsies. The aim of this study was to assess the quality and diagnostic accuracy of non-targeted liver biopsies at our institution.

Methods: A single-centre retrospective analysis was used to examine non-targeted liver biopsies performed between 1^st June 2021 and 1^st November 2023. Data was collected on procedural details [interventionalist, biopsy method (percutaneous vs. transjugular vs. laparoscopic), and needle size], biopsy specimen characteristics (number of samples, specimen length, number of portal tracts), and histopathology. The primary outcome was the proportion of diagnostic specimens. Secondary outcomes included specimen length and portal tract number.

Results: There were 169 liver core biopsies identified in the study period, of which 68 were non-targeted. 83.8% (n=57) were performed by interventional radiology (IR), of which 80.9% (n=55) were percutaneous (median needle gauge 16, IQR 14-18) and 3% (n=2) transjugular. 14.7% (n=10) of biopsies were obtained laparoscopically, and 1.5% (n=1) via endoscopic ultrasound (EUS). The median sample number per biopsy was 2 (IQR 1-2), yielding 142 individual samples of median length 14mm (IQR 8.5-17). Median aggregate length per biopsy was 24mm (18-36). Portal tract number was reported in 58.8% (n=40) of biopsies [median 9 (IQR 6.5-12)], and 20% (n=8) of these had <6 portal tracts. Of the 68 biopsies, 58.8% (n=40) were diagnostic, 20.6% (n=14) were non-diagnostic, and 20.6% (n=14) were partially diagnostic. The diagnostic biopsies had a greater median individual sample length [14mm (IQR 9-18) vs.13mm (IQR 8-16), p=0.047]. A greater number of reported portal tracts was observed in diagnostic and partially diagnostic specimens combined compared to non-diagnostic specimens [median 9 (IQR 7-12) vs. 5.5 (IQR 2-10), p=0.059].

Conclusion: Diagnostic accuracy relies on the quality of the diagnostic tool in question. Our audit revealed a deficit in the reporting of non-targeted liver biopsy results, particularly with respect to the number of portal tracts. Of the biopsies which had portal tract numbers reported, 20% did not meet the Royal College of Pathologists of Australasia criteria for minimum number of 6 portal tracts. Predictors of non-diagnostic biopsies in our analysis included smaller individual core sample length and portal tract number. These findings are informative and currently guiding changes to practice with the aim to improve liver biopsy quality.

250

A specialist liver home-based nursing program following inpatient admission facilitates earlier discharge from hospital: A single-centre analysis

Leya Nedumannil¹, Catherine Yu¹, Kristen Peake¹, Vanessa Lowen¹, Kendall Fitzpatrick¹, Mustafa Mohamedrashed¹, Mayur Garg^1,2, Diana Lewis¹ and Siddharth Sood^1,2

¹The Northern Hospital, Epping, Australia; ²The University of Melbourne, Parkville, Australia

Background and Aim: Liver At Home (L@H) is a 3-month liver-focused home-based program at a tertiary metropolitan health service. It provides continued outpatient care for patients with cirrhosis following hospitalisation through regular home visits and telehealth reviews (three times a week in the first four weeks, then weekly for eight weeks). We hypothesised that the availability of L@H would facilitate earlier inpatient discharge and reduce hospital length of stay (LOS) for patients subsequently enrolled to L@H.

Methods: Patients with cirrhosis were enrolled to L@H between 01/03/2023-01/03/2024. Only index referrals to L@H were analysed (i.e. re-enrolments excluded). Estimated discharge date (EDD) from hospital was provided by the ward Gastroenterology team. Exclusion criteria from L@H included patient preference not to participate, residence outside the hospital catchment, and high-risk score on safety screening. LOS in L@H patients were compared to patients with cirrhosis who were not enrolled, using an intention to treat analysis.

Results: 71 initial referrals for patients with cirrhosis were made to L@H, of which 47 were enrolled and 24 were not. Patient demographics, cirrhosis severity, and reason for admission were similar in both groups (Table 1). Median hospital LOS in days was 3-(IQR 2-3) in L@H vs 5-(IQR 3-6) in non-L@H patients, p=0.43. Whilst non-L@H patients had a higher proportion admitted with hepatic encephalopathy (p=0.14) and variceal bleeding (p=0.07), median LOS in this subset did not significantly differ from L@H patients [6-(IQR 4-7) vs 8-(IQR 5-11), p=0.19]. Based on EDD, earlier than anticipated inpatient discharge was facilitated by L@H in 31.9%-(n=15) of enrolled patients. 21.3%-(n=10) of these patients were discharged early by one day, and 10.6%-(n=5) patients by two days. L@H primarily enabled earlier hospital discharge in patients admitted for alcohol-associated hepatitis [40%-(n=6)] and uncomplicated ascites [27%-(n=4)], where blood test and fluid status monitoring could be safely conducted at home.

Conclusion: Patients with cirrhosis enrolled to L@H had a shorter median hospital LOS by two days relative to a similar non-enrolled cohort. Our findings suggest that L@H may have facilitated earlier discharge from hospital in a subset of these patients, especially those with alcohol-associated hepatitis or uncomplicated ascites, who could be effectively observed at home with close support provided through specialist liver nurse and hepatologist input. Analogous home-based care programs to L@H may help to expedite safe hospital discharge in a select group by engendering confidence in physicians that their patients will receive ongoing adequate specialist management in the community.

251

Hepatocellular carcinoma confers prolonged hospital admissions but lower 30-day readmission rates when compared to patients with cirrhosis only

Oliver Moore, Eric Kalo, Rajiv Kurup and Golo Ahlenstiel

Blacktown Clinical School, Blacktown, Australia

Background and Aim: Cirrhosis and hepatocellular carcinoma (HCC) are associated with high levels of mortality and morbidity, especially when disease course is punctuated by an acute decompensation event. Population based evaluation of trends in presentations, length of stay (LOS) and time to mortality can help in the development and implementation of effective public health policy. We assessed and compared mortality and morbidity trends for patients experiencing an acute decompensation event with HCC and cirrhosis versus those with cirrhosis and no HCC to identify vulnerable patient populations.

Methods: We retrospectively analysed data from 1538 patients with cirrhotic liver disease who presented to Blacktown hospital between 2010 and 2022 with an acute decompensation event; ascites requiring therapeutic intervention, hepatic encephalopathy, hepatic hydrothorax and acute variceal bleeds. LOS, time to death and readmission as well as demographic data were recorded, with comparisons of means between patients with and without HCC. Independent predictors of 30-day readmission were selected for the entire cohort, patients with only cirrhosis and those with HCC.

Results: 128 patients (8.3%) had diagnosed HCC at the time of discharge following an acute admission. Patients with HCC were significantly older (61.34 ± 9.72) than those without (58.94 ± 11.75) with significantly more having an aetiology relating to hepatitis C infection (41.41% vs 28.16%, p=0.002). These patients also had significantly longer admissions (8.25 ± 9.02 vs 6.96 ± 9.19, p<0.001) with greater rates of in-hospital mortality (25.00% vs 5.55%, p<0.001). As expected, patients with HCC had higher 90-day mortality (47.65%) than those without (15.60%, p<0.001). 30-day readmission rates were higher in those without HCC (37.66%) than those with (23.21%, p=0.029). For cirrhotics without HCC, younger age, male sex and viral aetiology of disease were associated with readmission, whilst gastroscopy for acute variceal bleeding was protective. There were no predictors for readmission in patients with HCC including BCLC, MELD score, ALBI class and admission or discharge on weekends.

Conclusion: Patients with HCC have longer admissions with increased mortality when compared to those with cirrhosis but no HCC. However, those with HCC also had lower 30-day readmission rates. There are no clear predictors for acute hospital representation emphasising the importance of early and regular follow up.

253

Is nesting addiction medicine and hepatology care in the outpatient setting worthwhile? A retrospective case series at a single tertiary centre

Rachit Gupta¹, Jecinn Wong¹, Christine Hallinan², Jacinta Holmes¹, Alexander Thompson¹, Adam Pastor¹ and Yvonne Bonomo¹

¹St Vincent's Hospital Melbourne, Fitzroy, Australia; ²Department of General Practice, University of Melbourne, Parkville, Australia

Background and Aim: Guidelines for management of substance use disorders (SUD) and alcohol use disorder (AUD) complicated by liver disease suggest input from both addiction medicine and hepatology physicians. Although integrated care models are well researched and implemented across other specialities, patients with SUD/AUD rarely have access to integrated addiction medicine and hepatology care in the outpatient setting. Patients are limited from accessing streamlined models of collaborative care for a number of reasons including healthcare provider shortages, stigma, medical and psychiatric complexity, increasing prevalence and resource disparities according to geographic location.

Methods: We conducted a retrospective review of medical records (n= 81) of an integrated outpatient clinic with both addiction medicine specialists and hepatologists at a tertiary hospital in Melbourne, Australia.

Results: A total of 81 outpatient integrated appointments over a 31-month period (February 2021 – September 2023) were completed for 54 distinct patients. Mean age was 58 years and the majority were male (n = 35, 64.8%). Most patients met criteria for AUD (n = 48, 88.9%) with all patients (n = 54, 100%) reporting alcohol as their primary substance of use. 20/54 (37%) patients had transient elastography (TE) results available with a median of 8.7 kPa and 5/20 (20%) having TE > 12.5 kPa. Interventions offered in the clinic included continuation or commencement of anticravings medications for alcohol use disorder, motivational interviewing and referral to specialist alcohol and drug counselling (Table 1). For patients who had more than one integrated appointment (n = 17), 2 (11%) reported reduction in alcohol use and 8 (41%) reported alcohol cessation in the preceding one month.

Conclusion: An integrated model of care addressed a number of barriers for people with SUDs and chronic liver disease and that access to multispecialty care in the one outpatient appointment was achievable. 10/17 (59%) patients who had more than one integrated appointment reported either reduction or cessation in their alcohol use in the preceding one month to their appointment. Further large-scale prospective studies are required to assess the implementation and cost effectiveness of real-world integrated models of care in this population.

259

Piloting an anti-inflammatory diet in patients with metabolic dysfunction associated steatotic liver disease

Wai See Ma

Blacktown Hospital, Blacktown, Australia

Background and Aim: Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is rising in prevalence to 30% in the adult population worldwide¹. This is in parallel with rising worldwide prevalence of metabolic disorders such as obesity, dyslipidaemia, hypertension and insulin resistance^1-3. There is, therefore, substantial economic burden^4-6 associated with the disease. With limited therapeutic options, the mainstay of treatment remains as lifestyle intervention involving weight loss through diet and exercise. The Mediterranean Diet, a part of an anti-inflammatory diet, is often recommended¹ to these patients given its associated improvements in cardiovascular health and reduction in hepatic steatosis. The anti-inflamamtory diet itself, however, has not been studied as extensively in patients with MASLD. We therefore set out to investigate, via an observational study, to determine the impact of the anti-inflammatory diet on patients with MASLD.

Methods: 30 patients were recruited from Western Sydney, NSW. Patients age > 18, with known MASLD diagnosed via imaging, fibroscan and blood parameters were included. Patients with liver cirrhosis, concomitant liver disease and hepatocellular carcinoma were excluded. Prior to commencing the diet, a two week wash-in period was included to minimize baseline variability. Fasting bloods (liver function tests, metabolic markers and inflammatory markers), anthropometric measurements and a fibroscan were performed at enrolment, and at the end of the study. A pre-study dietary questionnaire was also conducted. The patients then embarked on a three month anti-inflammatory dietary intervention period, guided by a dietician.

Results: There was no significant difference in any of the blood parameters over the two week wash in period. At the end of the study, there was a global decrease in studied markers including anthropometric markers, although only ALT (57± 36.8, 42.37± 22.7, p=0.0476) and CAP (310.7±46.7, 287.1±51.1, p=0.0475) on fibroscan had a statistically significant decrease.

Conclusion: Whilst our feasibility study involved low patient numbers, we demonstrated that improvement in hepatic steatosis and liver function tests in the absence of significant weight loss can be achieved via the anti-inflammatory diet. The limitations of our study included low patient numbers and a short timeframe; therefore, further studies will need to be conducted to be able to draw more substantial conclusions on the subject.

References

1. Rinella, M.E., et al., AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology, 2023. 77(5): p. 1797-1835.

2. Estes, C., et al., Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology, 2018. 67(1): p. 123-133.

3. Le, P., et al., Population-based trends in prevalence of nonalcoholic fatty liver disease in US adults with type 2 diabetes. Clinical Gastroenterology and Hepatology, 2019. 17(11): p. 2377-2378.

4. Younossi, Z.M., et al., The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology, 2016. 64(5): p. 1577-1586.

5. Younossi, Z.M., et al., Economic and clinical burden of nonalcoholic steatohepatitis in patients with type 2 diabetes in the US. Diabetes care, 2020. 43(2): p. 283-289.

6. Schattenberg, J.M., et al., Disease burden and economic impact of diagnosed non-alcoholic steatohepatitis in five European countries in 2018: a cost-of-illness analysis. Liver International, 2021. 41(6): p. 1227-1242.

261

Enhancing the diagnosis of metabolic dysfunction-associated steatohepatitis with advanced liver fibrosis using FibroScan-aspartate aminotransferase (FAST) score

Wei Ling Teh, James Fiori, Wendy Lam, Christopher Welman and Oyekoya Ayonrinde

Fiona Stanley Hospital, Perth, Australia

Background and Aim: Over 30% of the global population has metabolic dysfunction-associated steatotic liver disease (MASLD), among whom those with metabolic dysfunction-associated steatohepatitis (MASH) are at highest risk of adverse liver and cardiometabolic outcomes. Various non-invasive tests (NITs) have been proposed to diagnose MASH without requiring liver biopsy. Studies have shown that the risk of liver-related events becomes exponentially higher with advanced liver fibrosis, i.e. fibrosis stages F3 and F4. We aimed to compare different NITs in predicting MASH with a NAFLD activity score (NAS) ≥4 with advanced fibrosis (MASH-F3/4) in a Western Australia cohort.

Methods: Retrospective study including patients with suspected MASH, who underwent liver biopsy between February 2017 and May 2024. Patient demographic characteristics, anthropometry, blood tests, and FibroScan® results performed within 6-months of the biopsy were recorded. We calculated the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, AST to platelet ratio index (APRI) and Fibrosis-4 (FIB-4) index. We also calculated the FibroScan-aspartate aminotransferase (FAST) score, utilising controlled attenuation parameter (CAP) (dB/m), liver stiffness measurement (LSM) (kPa), and AST (U/L). We excluded patients with significant alcohol use, defined as >20g/d and 30g/d alcohol intake in females and males respectively, and those with other liver disorders. We examined the utility of the different NITs for MASH with F3/4 fibrosis.

Results: 64 patients (women 45 (70.3%)) were included. There were 32 patients (50%) with MASH + NAS ≥4 + ≥F3. Patients with MASH with NAS≥4 and advanced fibrosis had significantly higher mean AST, APRI, FIB4, LSM and FAST scores, compared with those without MASH-F3/4 (p<0.05 for all), whereas the mean age at biopsy, BMI, ALT, AST/ALT ratio and CAP were not significantly higher.

Using multivariable logistic regression analysis, a FAST-score ≥0.67 was independently associated with increased risk of MASH-F3/4 (OR 8.13, 95% CI 1.42-46.63, p=0.02), while the absence of type 2 diabetes mellitus was associated with reduced risk of a histological diagnosis of MASH-F3/4 (OR 0.09, 95% CI 0.01-0.67, p=0.02), after adjusting for other covariates. Age (OR 1.00, 95%CI 0.94-1.07, p=0.93), gender (OR 1.43, 95%CI 0.34-5.96, p=0.62), BMI (OR 0.93, 95%CI 0.82-1.06, p=0.26), FIB-4 score ≥2.67 (OR 5.47, 95%CI 0.78-38.55, p=0.09) and FibroScan® LSM ≥10kPa (OR 1.28, 95%CI 0.27-6.03, p=0.75), were not significantly associated with MASH-F3/4.

Conclusion: AST is an important liver enzyme in assessment of liver fibrosis, being a component of both the FIB-4 score and FAST score. In our study, a FAST score ≥0.67 was useful for predicting MASH with advanced liver fibrosis, while the absence of type 2 diabetes mellitus appeared protective. We found FIB-4 score to be a useful pre-screening test prior to proceeding to liver elastography or biopsy in those with suspected MASH with advanced fibrosis.

264

Predicting hepatic decompensation in patients with metabolic dysfunction-associated fatty liver disease-related cirrhosis: The ABID-LSM model

Luis Calzadilla Bertot^1,2, Anna Soria³, Alba Jimenez-Masip⁴, Isabel Serra⁵, Teresa Broquetas⁶, Mercedes Vergara⁷, Adria Rodriguez⁸, Carles Aracil⁹, Octavi Bassegoda³, Sergio Muñoz Martínez⁴, Jose Carrion⁶, Albert Pardo⁸, Juan M Pericàs⁴, Isabel Graupera³ and Leon A Adams^1,2,10,11,12

¹Medical School, The University of Western Australia, Australia; ²Department of Hepatology and Liver Transplantation Service, Sir Charles Gairdner Hospital, Australia; ³Servei d'Hepatologia, Clínic Barcelona, Spain; ⁴Liver Unit, Vall d’Hebron University Hospital, Spain; ⁵Departament Hepatology, Dr Josep Trueta Hospital, Spain; ⁶Liver Section, Gastroenterology Department, Hospital del Mar, Spain; ⁷Unidad Hepatología Servicio Digestivo, Hospital Universitari Parc Taulí, Spain; ⁸Servicio de Aparato Digestivo, Hospital Universitari de Tarragona Joan XXIII, Spain; ⁹Secció d´Hepatologia. Servei de Digestiu, Institute of Biomedical Research, Spain; ¹⁰Liver Unit, Vall d’Hebron University Hospital, Spain; ¹¹Liver Section, Gastroenterology Department, Hospital del Mar, Spain; ¹²11111, 11111,

Background and Aim: Metabolic dysfunction-associated fatty liver disease (MAFLD) is becoming a major cause of cirrhosis leading to decompensation and death. Predicting the risk of hepatic decompensation is crucial for prognostication and identification of those who may benefit from therapy. We previously developed a predictive tool of hepatic decompensation for MAFLD patients with cirrhosis consisting of AST/ALT ratio, bilirubin, international normalized ratio, Type 2 diabetes and esophageal varices (ABIDE model). The ABIDE model includes the assessment of esophageal varices by gastroscopy. We aimed to validate a modified ABIDE model by replacing esophageal varices with liver stiffness measurement (LSM) by transient elastography (TE) and compare the modified model with other risk prediction models.

Methods: This was a multicenter (8 tertiary centers, Catalonia, Spain) retrospective cohort study of 388 patients with compensated cirrhosis due to MAFLD conducted from January 2009 to December 2018. Patients with previous HCC or hepatic decompensation, MELD score ≥15 or Child Pugh ≥7 or prior liver transplantation were excluded. ABIDE model, NFS, FIB-4, ALBI, ALBI-FIB-4 and NAFLD decompensation risk score were computed at baseline. Competing risk regression, time dependent area under the curve (tAUC), net reclassification (NRI) and integrated discrimination improvement (IDI) were used to assess incidence of outcomes and prognostic measures respectively. Estimation and comparison were made between ABIDE model, a modified ABIDE model replacing varices with LSM by TE and LSM alone. K and D statistic, calibration slope and Integrated Brier score were calculated as measures of discrimination, calibration, and overall accuracy.

Results: Hepatic decompensation occurred in 105 (27%) patients during a median follow-up of 31 months (range 18-60). Hepatic decompensation occurred in 20% in the subset of patients (n=273) with available LSM. The predictive accuracy at 5 years of ABID-LSM (tAUC 0.80) was better than ABIDE (tAUC 0.75, p=0.03) and LSM (tAUC 0.63, p<0.001). ABID-LSM showed better net reclassification, IDI compared to ABIDE and LSM. Discriminative measures were better for ABID-LSM (k-statistic 0.73, D –statistic 1.91) than ABIDE (k-statistic 0.71, D –statistic 1.77) and LSM (k-statistic 0.68, D –statistic 1.65). The cumulative incidence of hepatic decompensation at 5 years was significantly higher using a model threshold of ≥7.1 (22 vs 5%, sHR=5.3, 95% CI 1.71-7.89; p<0.001) (Figure). ABID-LSM calibrated well (slope 0.99) with excellent overall performance (Integrated Brier score 0.15). The ABID-LSM model had better prediction values at 5 years (tAUC=0.80) than NFS and ALBI (tAUC= 0.72), FIB-4 (tAUC= 0.74), ALBI-FIB-4 (tAUC= 0.73) and NAFLD decompensation risk score (tAUC= 0.65) (all p<0.001).

266

Hepatocellular carcinoma and lifestyle: How do dietary patterns differ in those with metabolic and non-metabolic dysfunction associated fatty liver disease?

Nikil Vootukuru¹, Elena George², Nicholas Batt¹, Surbhi Sood², Beverly Rodrigues¹, Rohit Sawhney¹, Alex Hodge¹, Stephen Bloom¹, Carol McCrae¹, Stuart Roberts³, Anouk Dev⁴, Sally Bell⁴, Alexander Thompson⁵, Marno Ryan⁵, William Kemp³, Paul Gow⁶, Siddharth Sood⁷ and Amanda Nicoll¹

¹Eastern Health, Melbourne, Australia; ²Deakin University, Melbourne, Australia; ³Alfred Health, Melbourne, Australia; ⁴Monash Health, Melbourne, Australia; ⁵St Vincents Health, Melbourne, Australia; ⁶Austin Health, Melbourne, Australia; ⁷Melbourne Health, Melbourne, Australia

Background and Aim: Metabolic-Associated Fatty Liver Disease (MAFLD) is now a major cause of liver morbidity and mortality, including hepatocellular carcinoma (HCC). Unhealthy dietary patterns are more likely to predispose to HCC development. The aim of this study was to explore dietary patterns among patients with established HCC comparing those with and without MAFLD.

Methods: A multicentre, prospective cohort analysis of newly diagnosed HCC patients at six hepatology centres in metropolitan Melbourne (Victoria, Australia) was conducted from October 2020 to July 2022. A subset of seventy participants out of 313 recruited (22.4%) completed a three-day food diary. Food diaries were self-reported written records documenting the type, brand, and quantities of food and beverages consumed by participants, and recipes were provided where appropriate; they were entered and analysed the food diaries using the software FoodWorks 9™. Food diaries were used to measure adherence to MedDiet Score (0–45 points); higher scores indicating higher adherence. Demographic and clinical data was prospectively collected from hospital electronic medical records. All statistical analysis for this subgroup analysis was performed using the R programming environment.

Results: Seventy patients with HCC were included in the study of which: 35 (50%) had no features of MAFLD (non-MAFLD) and 35 (50%) had features of MAFLD. There were no significant differences in baseline demographics between the groups except for age (Table 1). Cirrhosis was present in 77% of MAFLD HCC, compared to 83% in non-MAFLD group, and the majority were Child-Pugh A (55.7%) in both groups. An exploratory univariable analysis identified significant differences in daily energy intake (kJ) (p=0.03), processed meat serves (p=0.04), legumes serve (p=0.02), and yoghurt serves (p=0.03) but interestingly the daily energy intake (kJ) and processed meat serves were higher among the non-MAFLD group. A multivariable analysis adjusting for energy, gender, BMI and age showed that processed meat serves (p = 0.04) were higher among non-MAFLD than MAFLD groups. There were no other dietary differences identified both on univariable and multivariable analysis between the non-MAFLD and MAFLD groups. The MedDiet Score which evaluates adherence to mediterranean dietary patterns was not significantly different between both groups.

Conclusion: Differences in dietary patterns in patients with liver injury may contribute to the occurrence of HCC in patients with MAFLD, and possibly in non-MAFLD. However, further studies are required to explore habitual dietary intake and patterns that predispose to development of HCC

276

Impacts of COVID-19 on HCC care cascade: maintained surveillance rates and improved linkage to care

Joan Ericka Flores^1,2, Alexander Thompson^1,2, Thai Hong^1,2, Stuart Roberts³, Amanda Nicoll⁴, Zina Valaydon⁵, Marno Ryan^1,2, Marie Sinclair⁶, Gauri Mishra⁷, William Kemp³, Ammar Majeed³ and Jessica Howell^1,2

¹St Vincent's Hospital Melbourne, Fitzroy, Australia; ²University of Melbourne, Clayton, Australia; ³Alfred Health, Melbourne, Australia; ⁴Eastern Health, Box Hill, Australia; ⁵Western Health, Footscray, Australia; ⁶Austin Health, Heidelberg, Australia; ⁷Monash Health, Clayton, Australia

Background and Aims: The Cancer Council of Australia first released the Optimal Cancer Pathway Recommendations of Hepatocellular Carcinoma (HCC OCP) in 2015, which include recommended time intervals for each step in the HCC care cascade: from referral to multidisciplinary HCC meeting (MDT) review, specialist care and treatment. ‘Lockdown restrictions’ in Melbourne, Victoria were implemented from March 2020 affecting access to pathology, radiological and outpatient services, leading to a transition to virtual telehealth clinics and MDTs, and HCC surveillance scans delivered in the community. The aim of this study was to describe the HCC cascade of care, concordance with HCC OCP recommendations and determine the impact of COVID19 lockdown restrictions in Victoria.

Methods: Incident HCC cases were prospectively identified over the period of 1^st January 2018-31^st December 2021 from six tertiary hospital sites with referrals from urban and rural locations. ‘Pre-lockdown’ cases were diagnosed prior to March 31st 2020, and ‘during-lockdown’ after. Demographic and clinical data including HCC stage, treatment and dates of each HCC OCP step were obtained from the hospital electronic medical record and HCC MDT databases. Proportion of concordance, median time intervals and interquartile ranges between HCC care steps were compared against HCC OCP recommendations: 14 days from referral to MDM presentation/attendance at specialist review; 28 days for staging/investigation time from referral to diagnostic and management consensus; 28 days from management decision to treatment receipt.

Results: A total of 1013 incident HCC cases were identified, with a male preponderance (n=820, 81%) and median age of 66 years (IQR 59-74 years). Cirrhosis was present in 83% of cases (n=842), of whom 29% had a diagnosis of cirrhosis made at the time as HCC. Early (BCLC 0-A) stage (n=482) occurred in 47%. 42% of all cases (n=424) diagnosed through a surveillance program, with no significant variation across the years (p=0.423). Of the 928 cases where referral information was available, 70% (n=646) were discussed at an MDT within two weeks of referral as recommended by HCC OCP guidelines (median time 6 days (IQR 3, 9 days); 63% (n=596) achieved the recommended 4 weeks from time of referral to management consensus (median time 9 days (IQR 5, 16 days). Of 957 cases where data were available, the recommended time from management consensus to treatment receipt was achieved in 30% (n=287) of cases, with a median time of 19 days (IQR 12, 24 days). There were 558 incident HCC cases identified pre-lockdown (54%) and 469 cases diagnosed during-lockdown. There was no significant difference in the proportion of individuals with known risk factors of cirrhosis and chronic hepatitis B undergoing surveillance (64%, n=221 vs 64% n=185, p=0.894). However, the proportion of cases concordant with recommended time from referral to MDT significant increased during from 64% (n=334) to 76% (n=316) (p<0.0001), median interval time reduced from 7 days (IQR 4,10) to 6 days (IQR 2, 9) in concordant cases. Similarly, investigation time recommendation concordance increased from 58% (n=306) to 69% (n=289) (p=0.001). There was a significant decrease in the proportion receiving timely treatment receipt during lockdown (33% n=175 vs 27% n=112 p=0.03). There was a decrease in the proportion of concordant non-surgical treatments from 42% (n=129) to 37% (n=83), though not statistically significant (p=0.117).

Conclusion: These data highlight effective successful implementation of telehealth clinics and virtual meetings, leading to an improvement in linking new HCC cases to specialist MDM for follow up during. However, timely treatment receipt was significantly impacted by lockdowns, seen particularly in non-surgically treated cases. HCC surveillance uptake remained suboptimal but were maintained during lockdowns through increased use of community radiology services. These data highlight the need for increased resource allocation to enable timely receipt of HCC surveillance and management.

277

Efficacy and safety of bulevirtide 2 mg or 10 mg monotherapy for chronic hepatitis delta at 96 weeks: Results from an interim analysis of a phase 3 randomized study

Heiner Wedemeyer¹, Soo Aleman², Maurizia Brunetto^3,4, Antje Blank⁵, Pietro Andreone⁶, Pavel Bogomolov⁷, Vladimir Chulanov⁸, Nina Mamonova⁹, Natalia Geyvandova¹⁰, Viacheslav Morozov¹¹, Olga Sagalova¹², Tatyana Stepanova¹³, Dmitry Manuilov¹⁴, Renee-Claude Mercier¹⁴, Qi An¹⁴, Aurelie Freismuth¹⁵, John F Flaherty¹⁴, Anu Osinusi¹⁴, Audrey Lau¹⁴, Julian Schulze zur Wiesch¹⁶, Markus Cornberg¹, Stefan Zeuzem¹⁷ and Pietro Lampertico^18,19

¹Clinic for Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover; ²Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Heidelberg; ³Hepatology Outpatient Medical Clinic, University Hospital Hamburg-Eppendorf, Hamburg; ⁴Department of Medicine, University Hospital Frankfurt, Frankfurt am Main, Germany; ⁵Department of Infectious Diseases, Karolinska University Hospital/Karolinska Institute, Stockholm, Sweden; ⁶Hepatology Unit, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa; ⁷Department of Clinical and Experimental Medicine, University of Pisa, Pisa; ⁸Internal Medicine, University of Modena and Reggio Emilia, Modena; ⁹Foundation IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoDivision of Gastroenterology and Hepatology; ¹⁰CRC “A. M. and A. Migliavacca” Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; ¹¹Moscow Regional Clinical Research Institute n.a. M.F. Vladimirsky, State Budgetary Institution of Health Care of Moscow Region; ¹²Sechenov University; ¹³FSBI National Research Medical Center for Phthisiopulmonology and Infectious Diseases of the Ministry of Health of the Russian Federation; ¹⁴LLC Clinic of Modern Medicine, Moscow; ¹⁵Stavropol Regional Hospital, Stavropol; ¹⁶LLC Medical Company Hepatolog, Samara; ¹⁷South Ural State Medical University, Chelyabinsk, Russian Federation; ¹⁸Gilead Sciences, Inc., Foster City, USA; ¹⁹Gilead Sciences, Pty Ltd, Melbourne, Australia

Background and Aim: Bulevirtide (BLV) is a first-in-class, entry inhibitor for chronic hepatitis delta (CHD) which was conditionally approved in the EU in July 2020. Results from the W48 primary endpoint analysis for MYR301 (NCT03852719), a phase 3 randomized study, showed monotherapy with BLV at 2mg or 10mg/day given subcutaneously was superior to no active anti-HDV treatment based on the combined viral and biochemical response. Efficacy was similar at the 2 dose levels and BLV was generally safe and well tolerated. Here, we present findings from the predefined W96 interim analysis of this study.

Methods: 150 patients with CHD were randomized (1:1:1) and stratified based on the presence/absence of compensated cirrhosis as follows: Arm A: no active hepatitis delta virus (HDV) treatment for 48W followed by BLV 10mg/day for 96W (n=51), and in arm B or C: immediate treatment with BLV at 2mg/day (n=49) or 10mg/day (n=50), respectively, each for 144W, with follow-up of 96W after end of treatment (up to W240). Combined response was defined as undetectable HDV RNA or decrease by ≥2 log₁₀ IU/mL from baseline and alanine aminotransferase (ALT) normalization; other endpoints included viral response (undetectable HDV RNA or ≥2 log₁₀ IU/mL decrease from baseline), ALT normalization, log₁₀ change in HDV RNA, and change in liver stiffness (LS) by transient elastography.

Conclusion: BLV continues to be safe and well tolerated as monotherapy for CHD through W96. Virological and biochemical responses increased with longer term therapy.

278

Continued treatment of early virologic nonresponders or partial responders with bulevirtide monotherapy for chronic hepatitis delta leads to improvement in virologic and biochemical responses: Results from an integrated analysis at week 96

Pietro Lampertico^1,2, Heiner Wedemeyer³, Maurizia Brunetto^4,5, Pavel Bogomolov⁶, Tatyana Stepanova⁷, Marc Bourlière⁸, Helène Fontaine⁹, Grace M Chee⁹, Dmitry Manuilov⁹, Qi An⁹, Aurelie Freismuth¹⁰, Audrey Lau⁹, Ben Da⁹, John F Flaherty⁹, Renee-Claude Mercier⁹, Catherine Frenette⁹, Anu Osinusi⁹, George Sebastian Gherlan^11,12, Adrian Streinu-Cercel¹³, Stefan Zeuzem¹⁴, Markus Cornberg³, Dominique Roulot¹⁵, Fabien Zoulim¹⁶, Soo Aleman¹⁷ and Tarik Asselah¹⁸

¹Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; ²CRC "A.M. and A." Migliavacca Center for the Study of Liver Disease, University of Milan, Milan, Italy; ³Clinic for Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany; ⁴Hepatology Unit, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa, Italy; ⁵Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; ⁶State Budgetary Institution of Health Care of Moscow Region, Moscow Regional Clinical Research Institute n.a. M.F. Vladimirsky, Moscow, Russian Federation; ⁷LLC Clinic of Modern Medicine, Moscow, Russian Federation; ⁸Hôpital Saint Joseph, Marseille, France; ⁹Gilead Science, Pty Ltd, Foster City, USA; ¹⁰Gilead Sciences, Pty Ltd, Australia; ¹¹Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; ¹²Dr. Victor Babes Foundation, Bucharest, Romania; ¹³Matei Bals National Institute of Infectious Diseases, Bucharest, Romania; ¹⁴University Hospital Frankfurt, Frankfurt am Main, Germany; ¹⁵Université Sorbonne Paris Nord, Bobigny, France; ¹⁶Hospital Croix Rousee, Lyon, France; ¹⁷Karolinska University Hospital/Karolinska Institute, Stockholm, Sweden; ¹⁸Hôpital Beaujon, Université de Paris, Clichy, France

Background and Aim: Bulevirtide (BLV) is approved in Europe for chronic hepatitis delta (CHD). Virologic responders (VR) were defined as having undetectable hepatitis delta virus (HDV) RNA or ≥2-log₁₀ IU/mL decline from baseline (BL). Optimal BLV monotherapy duration and whether continued therapy will benefit patients who are early virologic nonresponders (NR) or partial responders (PR) are unclear. This integrated analysis evaluated continued BLV monotherapy in patients without virologic response after W24.

Methods: Results from patients after BLV monotherapy for 96W in the Phase 3 (MYR301; NCT03852719) and Phase 2 (MYR204; NCT03852433) studies were included. NR and PR were defined as having HDV RNA declines of <1 log₁₀ IU/mL and ≥1 but <2 log₁₀ IU/mL. Rates of alanine aminotransferase (ALT) within normal limits [WNL] were compared.

Results: 141 CHD patients (47 BLV 2mg; 94 BLV 10mg) were evaluated. At BL, 67% were male, 87% White, 43% had cirrhosis, 40% received concomitant nucleos(t)ide analogues, and 50% had prior interferon exposure. Mean (SD) HDV RNA was 5.2 (1.3) log₁₀ IU/mL; median (Q1, Q3) ALT was 94 (64, 136) U/L. At W24, 65% of patients were VR (58% with ALT WNL), 24% were PR (56% with ALT WNL), and 11% were NR (13% with ALT WNL) (Table). 49 patients were NR or PR at W24. Of the PR at W24, 74% were VR and 71% had ALT WNL by W96. Of the NR at W24, 47% were VR and 20% were PR by W96. A higher proportion of NR at W24 were VR at W96 among those receiving BLV 10mg (80%) vs BLV 2mg (30%). Among W24 NR or PR, mean BL HDV RNA did not predict viral response at W96. Median (Q1, Q3) BL ALT was higher in NR (138 [112, 196] U/L) vs VR (79 [53, 113]) and PR (95 [56, 150]) at W96. The mean (SD) HDV RNA change at W96 was −3.6 (1.1), −1.4 (0.3), and −0.2 (0.7) log₁₀ IU/mL for VR, PR, and NR. Median (Q1, Q3) ALT change at W96 among VR/PR/NR was −48 (−73, −12), −42 (−83, −6), and −67 (−102, −33) U/L. Among all NR at W96, ALT declined >50% from BL in 7/11 (3/11 achieved ALT WNL).

279

Efficacy and safety of bulevirtide in combination with pegylated interferon alfa-2a in patients with chronic hepatitis delta: Primary endpoint results from the phase 2b, open-label, randomized, multicenter study MYR204

Tarik Asselah¹, Pietro Lampertico^2,3, Heiner Wedemeyer⁴, Adrian Streinu-Cercel⁵, Victor Pantea⁶, Stefan Lazar⁷, Gheorghe Placinta⁶, George Sebastian Gherlan⁷, Pavel Bogomolov⁸, Tatyana Stepanova⁹, Viacheslav Morozov¹⁰, Vladimir Chulanov¹¹, Vladimir Syutkin¹², Olga Sagalova¹³, Vladimir Gorodin¹⁴, Dmitry Manuilov¹⁵, Renee-Claude Mercier¹⁵, Lei Ye¹⁵, John F Flaherty¹⁵, Aurelie Freismuth¹⁶, Anu Osinusi¹⁵, Audrey Lau¹⁵, Ben Da¹⁵, Marc Bourlière¹⁷, Vlad Ratziu¹⁸, Stanislas Pol¹⁹, Marie-Noëlle Hilleret²⁰ and Fabien Zoulim²¹

¹Hôpital Beaujon, Université de Paris, Clichy, France; ²Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; ³CRC "A.M. and A." Migliavacca Center for the Study of Liver Disease, University of Milan, Milan, Italy; ⁴Clinic for Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany; ⁵Matei Bals National Institute of Infectious Diseases, Bucharest, Romania; ⁶Infectious Clinical Hospital “T. Ciorba”, Chisinau, Moldova; ⁷Dr. Victor Babes Foundation, University of Medicine and Pharmacy “Carol Davila” Bucharest, Bucharest, Romania; ⁸State Budgetary Institution of Health Care of Moscow Region, Moscow Regional Clinical Research Institute n.a. M.F. Vladimirsky, Moscow, Russian Federation; ⁹LLC Clinic of Modern Medicine, Moscow, Russian Federation; ¹⁰LLC Medical Company Hepatolog, Samara, Russian Federation; ¹¹Sechenov University, Moscow, Russian Federation; ¹²Institute of Emergency Medicine n.a. NV Sklifosovsky, Moscow, Russian Federation; ¹³South Ural State Medical University, Chelyabinsk, Russian Federation; ¹⁴Specialized Clinical Infectious Diseases Hospital, Krasnodar, Russian Federation; ¹⁵Gilead Sciences, Inc., Foster City, USA; ¹⁶Gilead Science, Pty Ltd, Melbourne, Australia; ¹⁷Hôpital Saint Joseph, Marseille, France; ¹⁸CH Pitié-Salpétrière, Paris, France; ¹⁹Hôpital Cochin, France; ²⁰Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France; ²¹Hospital Croix Rousee, Lyon, France

Background and Aim: Bulevirtide (BLV) is a first-in-class entry inhibitor approved in Europe for the treatment of chronic hepatitis delta (CHD). This Phase 2 study (MYR204; NCT03852433) evaluated the safety and efficacy of BLV (2 and 10mg) with or without peginterferon alfa-2a (PegIFN) in patients with CHD and compensated liver disease.

Methods: 174 patients with CHD were randomized (1:2:2:2) and stratified based on the absence or presence of compensated cirrhosis to receive (A) PegIFN for 48w; (B) BLV 2mg+PegIFN or (C) BLV 10mg+PegIFN for 48w, followed by 48w of monotherapy with BLV 2mg or 10mg; or (D) BLV 10mg for 96w. All patients were followed for 48w after end of treatment (EOT). The primary endpoint was sustained virologic response at W24 after EOT (SVR24) defined as undetectable hepatitis delta virus (HDV) RNA (<LLOQ, target not detected) with predefined comparison between arms C and D.

Results: Owing to a communications embargo, W48 data were not available for this submission. We will include those data for presentation at the conference. Demographics and baseline characteristics were similar across arms. The majority were male (71%) and White (87%) with a mean age of 41 years (SD, 8.7). Overall, 35% had compensated cirrhosis, mean liver stiffness was 13.1 (7.72) kPa, mean HDV RNA was 5.3 (1.2) log₁₀ IU/mL, mean alanine aminotransferase (ALT) was 114.0 (94.8) U/L, 28% were on nucleos(t)ide analogue therapy, and 48% were interferon experienced. Efficacy and safety results are shown in the table. SVR24 was achieved by 17% in arm A, 30% in arm B, 46% in arm C, and 12% in arm D (P=.003; arm C vs D). ALT normalization and composite endpoint at W24 after EOT were superior with BLV 10mg+PegIFN vs monotherapy. Hepatitis B surface antigen loss was only observed with the combination. The most common adverse events (AEs) were leukopenia, neutropenia, thrombocytopenia, influenza-like illness, lymphopenia, and vitamin D deficiency. AEs observed in the BLV+PegIFN combination arms were similar to those with PegIFN monotherapy. BLV dose-dependent bile acid elevations were asymptomatic, and levels returned to baseline after EOT. Six patients (3%) discontinued treatment; none were assessed as related to BLV.

280

Investigating the safety of same day discharge following microwave ablation and transarterial chemoembolisation for hepatocellular carcinoma: A retrospective analysis and planned prospective study

Darshan Nitchingham, Peter Litwin, Olga Sukocheva, Kathy Pietris and Edmund Tse

Royal Adelaide Hospital Department of Gastroenterology and Hepatology, Adelaide, Australia

Background and Aim: Two common forms of treatment for Hepatocellular carcinoma (HCC) include microwave ablation (MWA) and transarterial chemo-embolization (TACE). Despite low complications rates, there is no clear guideline regarding the need for post-procedural hospitalization. Clinical practice thus varies between centres, from same day discharge following a period of observation, up to 4 days of routine hospitalisation. We are auditing the complication rates of locoregional therapy to assess the feasibility of same day discharge. We expect that any post-procedural complications would be identified in a 3 hour observation period leading to hospital admission and appropriate treatment.

Methods: We retrospectively collected all data from 1^st July 2021 to 30^th June 2023 for all patients undergoing TACE and MWA at one of the two major tertiary referral centres in South Australia with patients being referred from the entire state.

Results: A total of 126 patients were referred for locoregional therapy with a male predominance. 48 had MWA and 78 had TACE. Average LOS were 1.3 days and 1.0 days respectively. Complication rates were defined as either symptoms requiring further monitoring (eg isolated fever, nausea) or requiring additional intervention (eg. Administration of analgesia, interventional radiology procedure or surgery). Complication rates were 15% for MWA and 10% for TACE. 14 patients experienced minor complications following their procedures – mostly isolated fevers, abdominal pain requiring opiates, nausea and hypertension and mild liver enzyme derangement. Only two patients experienced a major complication that would require admission following the procedure – bleeding hepatic artery requiring embolization and right sided hydrothorax requiring drainage. All of the complications except for a variceal bleed 1 month post procedure were immediate and would have been identified during a routine 3 hour observation period.

281

Microbial-metabolite interactions in MAFLD cirrhosis: Insights from MiMeNet-driven metagenomic and metabolomic integration

Mohammad Karimi Moridani¹, Jason Behary^2,3, Annette Spooner⁴, Azadeh Safarchi⁵, Arcot Sowmya⁴, Amany Zekry^2,3 and Fatemeh Vafaee¹

¹School of Biotechnology and Biomolecular Sciences, UNSW, Sydney, Australia; ²Gastroetnerology and Heaptology Department, St George Hospital, Sydney, Australia; ³St George and Sutherland Clinical Campuses, UNSW, Sydney, Australia; ⁴Computer Science and Engineering- UNSW, Sydney, Australia; ⁵CSIRO, Sydney, Australia

Background: Emerging evidence confirms that gut microbiota and their related metabolites are crucial in the pathogenesis of metabolic-associated fatty liver disease (MAFLD). Our study aimed to elucidate the interrelationships between microbiome and metabolite profiles in MAFLD cirrhosis compared to matched controls. These findings could guide clinicians in modifying metabolite levels by altering microbiome composition, offering new therapeutic opportunities.

Methods: We conducted metagenomic and metabolomic characterisations using stool and serum samples from 58 participants, including 29 individuals with MAFLD-cirrhosis and 29 matched normal controls. Utilising the MiMeNet approach, a neural network-based tool, we predicted metabolite levels and identified the most accurate ones distinguishing MAFLD-cirrhosis from controls. MiMeNet generated a background distribution of Spearman correlation coefficients (SCCs) through data shuffling and cross-validated evaluations, setting a threshold for significantly well-predicted metabolites. Post-training, MiMeNet used learned network weights to produce a score matrix indicating microbial contributions to predicted metabolite levels.

Results: The top 20 well-predicted metabolites by MiMeNet are presented in Fig 1A and include cysteine-glutathione disulphide (indicative of oxidative stress), retinol (associated with MAFLD fibrosis), and certain glutamine conjugates (known to reduce oxidative stress and liver injury in MAFLD), which prominently differentiated the groups. Feature attribution scores for all microbiome-metabolite pairs were calculated using trained model weights, revealing that 270 microbiomes had at least one significant attribution score with a well-predicted metabolite. Positive scores indicated a positive influence on metabolite abundance, while negative scores indicated a negative influence. Microbiomes and metabolites were organised into modules using biclustering, revealing nine microbial modules and five metabolite modules (Fig 1B). A bipartite graph (Fig 1C) was created between microbiome and metabolite modules, with attribution scores representing the mean score within each block, demonstrating differential microbial/metabolite interactions between MAFLD cirrhosis and control groups.

283

Can the FibroScan-AST (FAST) score predict cardiometabolic risk?

James Fiori¹, Wei Teh¹, Wendy Lam¹ and Oyekoya Ayonrinde^1,2

¹Fiona Stanley Hospital; ²Medical School, The University of Western Australia, Crawley, Australia

Background and Aim: Cardiovascular disease (CVD) is the leading cause of mortality amongst patients with metabolic dysfunction associated steatohepatitis (MASH). More severe histological features of MASH are associated with higher CVD risk. Therefore, early identification of MASH severity allows opportunities for therapeutic strategies to reduce the burden of CVD. The FibroScan-AST (FAST) score identifies patients with MASH (defined histologically by a NAFLD Activity Score [NAS] ≥4 and significant fibrosis F ≥2). It utilises non-invasive measures of FibroScan® liver stiffness measurement (LSM) by vibration-controlled transient elastography and controlled attenuation parameter (CAP) in conjunction with aspartate aminotransferase (AST). We examined associations between FAST score and measures of cardiometabolic risk in patients with MASH.

Methods: Retrospective clinical records review of 77 patients who underwent liver biopsy for suspected MASH at a Western Australian tertiary hospital between March 2017 and November 2023. 13 patients were excluded as they did not have data to calculate FAST score. Data collected included body mass index (BMI), blood pressure, history of atherosclerotic cardiovascular disease (ASCVD), type 2 diabetes, smoking, AST, lipids and HbA1c. FibroScan results were reviewed for LSM and CAP. We calculated 5-year absolute CVD risk using the Australian Absolute CVD Risk Calculator. Associations were sought between FAST score, 5-year CVD risk, type 2 diabetes, HbA1c, and BMI. Descriptive data presented as median (IQR).

Results: 64 patients were included with a median age of 63 (56.8-69) years, with two-thirds female. Fifty-five patients had sufficient data available to calculate their 5-year CVD risk. Thirteen (23.6%) had established ASCVD. Twenty-two (40%) had a high 5-year CVD risk, ten (18.2%) intermediate risk and ten (18.2%) low risk. Eight patients (14.5%) experienced a major adverse cardiac event (MACE). Patients with established CVD had higher median FAST score than those without however this was not significant (0.75 vs 0.66, p=0.77). There was no significant difference in FAST scores between each 5-year CVD risk category (p=0.44). FAST score was significantly correlated with BMI (r_s=0.57, p<0.001). There was no significant difference in median FAST score for patients with diabetes mellitus compared to those without (0.66 vs 0.69, p=1.0). There was no significant correlation between FAST score and HbA1c (r_s =0.12, p=0.40).

285

Integrative machine learning model using multi-omics data for early prediction and biomarker identification of hepatocellular carcinoma

Annette Spooner¹, Jason Behary^2,3, Mohammad Karimi Moridani⁴, Azadeh Safarchi⁵, Arcot Sowmya¹, Amany Zekry^2,3 and Fatemeh Vafaee⁴

¹School of Computer Science and Engineering, UNSW, Sydney, Australia; ²Department of Gastroenterology and Hepatology, St George Hospital, UNSW, Sydney, Australia; ³St George and Sutherland Clinical Campuses, UNSW, Sydney, Australia; ⁴School of Biotechnology and Biomolecular Sciences, UNSW, Sydney, Australia; ⁵CSIRO, Sydney, Australia

Background: Integrating various types of 'omics data provides comprehensive insights into a patient's health, enhancing our understanding of complex diseases. This study aimed to develop a machine learning model for early prediction of primary hepatocellular carcinoma (HCC) using multiple 'omics data sources and to identify reliable biomarkers for early prediction of HCC.

Methods: We included a cohort consisting of 106 patients with early HCC from metabolic-associated liver disease (MAFLD-HCC, n=25), viral hepatitis-related HCC (non-MAFLD-HCC, n=25), MAFLD-related liver cirrhosis (MAFLD cirrhosis, n=28), and a control group of healthy individuals (CON, n=28). Subjects were matched for gender, age, and ethnicity, excluding those with portal hypertension or advanced liver disease/HCC. All participants underwent oral and stool microbiome testing (metagenomic) and serum cytokine and metabolomic (untargeted) testing. For each patient, clinical and biochemical (Path) data were included. To develop the model, we first trained a gradient boosting machine (GBM) classifier on each of the individual data modalities to test their predictive accuracy in classifying patients according to their disease status i.e. healthy controls (CON), MAFLD, and MAFLD and non-MAFLD related HCC. We then developed five different machine learning models capable of integrating multiple sources of omics data. Each method used a form of late integration, training a model on each ‘omics dataset independently and aggregating the results. We compared the predictive accuracy of these methods to each other, to that of a single classifier trained on the concatenated data and to that of the individual modalities. We also examined the stability of the biomarkers predicted by these methods. The methods tested were a) a simple ensemble using majority voting to aggregate the results from the different modalities; b) a meta-learner, learning from the outputs of each modality; c) the Adaboost algorithm, enhanced for multi-modal data; d) the PB-MVBoost algorithm and e) a mixture of experts model, which trains a classifier for each class versus all other classes and selects the most confident result for each patient. Predictive accuracy was measured using the Area under the Receiver Operating Curve (AUC) and the F1 score. Stability was measured using the relative weighted consistency index.

Results: Our results show that of the individual modalities, the cytokine data was the most predictive with an AUC of 0.8 and an F1 Score of 0.69 (±0.13), followed by the metabolomic data with an AUC of 0.76 and an F1 score of 0.62 (±0.16). However, the multi-modal models, integrating metagenomic, metabolomic, cytokine and demographic data, were able to differentiate the classes more accurately than either the individual modalities or a concatenation of modalities. The mixture of experts’ model was the most accurate model, with an AUC of 0.88 and an F1 score of 0.84 (±0.12). The key features that were predictive of HCC in each class are presented in Figure 1.

286

Predictors of mortality in hepatocellular cancer secondary to metabolic-dysfunction associated steatotic liver disease: a New Zealand cohort analysis

Vijay Dyavadi¹, Akhilesh Swaminathan^1,2 and Ed Gane^1,3

¹Health New Zealand, Auckland, New Zealand; ²University of Otago, Dunedin, New Zealand; ³University of Auckland, Auckland, New Zealand

Background and Aim: Metabolic-associated steatotic liver disease (MASLD) is highly prevalent and is a risk factor for hepatocellular carcinoma (HCC), which is associated with significant mortality. This study investigated predictors of mortality in HCC patients with MASLD (MASLD-HCC) in a nationwide cohort.

Methods: New Zealand patients aged ≥18 years with MASLD-HCC were retrospectively reviewed from a national database of all patients referred to an HCC multi-disciplinary meeting between 1998-2020. Univariable and multivariable logistic regression identified baseline variables that predicted 1-year mortality. Univariable and multivariable Cox’s proportional hazards models identified baseline variables associated with overall mortality.

Results: MASLD-related HCC was identified in 295/2296 patients; median age 72 years, 220 males, 196 European ethnicity, 173/229 obese and 218/286 had type-2-diabetes. Surveillance identified MASLD-related HCC in 76/295 patients; 200/272 had cirrhosis at HCC diagnosis; and 86 had curative treatment (31 resection, 33 ablation, 22 transplant). Median time to death was 10 months (IQR 3-22) and 212 patients died during the study period. Multivariable logistic regression identified AFP≥50μg/L (adjustedOR (aOR)=5.19, p<0.01), ALBI>-2 (aOR=5.33, p<0.01), tumour diameter (aOR=1.018, p<0.01), macrovascular invasion (aOR₌5.78, p=0.01) and extra-hepatic metastasis (aOR=7.04, p<0.01) being significantly associated with 1-year mortality. Overall mortality was predicted by AFP>50μg/L (adjusted hazard ratio (aHR)=2.24, p<0.01), FIB4 score (aHR=1.09, p<0.01), ALBI>-2 (aHR=1.63, p=0.05), tumour diameter (aHR=1.01, p<0.01) and macrovascular invasion (aHR=2.98, p<0.01) on multivariable analysis. Surveillance was not associated with 1-year (OR=0.38, p=0.24) or overall mortality (aHR=0.63, p=0.36) on multivariable analysis.

Conclusion: MASLD is an increasingly significant risk factor for HCC. Baseline AFP, FIB4 and ABLI score along with tumour size and presence of vascular invasion at diagnosis predicted overall mortality in MASLD-HCC. Surveillance did not improve mortality in MASLD-HCC. These results question the cost-effectiveness of HCC surveillance in comorbid elderly populations with MASLD-associated liver disease.

289

Muscle mass, frailty and cardiopulmonary exercise testing: correlations and impact on liver transplant outcomes

Shivangi Gupta¹, Ben Bull², May Kang³, Luis Calzadilla Bertot^1,4, Angus W Jeffrey¹, Christopher Welman⁵, Bhajan Singh^6,7,8, Leon A Adams^1,4, George Garas¹, Gerry MacQuillan¹, Michael Wallace¹, Briohny Smith¹, Luc Delriviere⁹ and Gary P Jeffrey^1,3

¹Western Australian Liver Transplant Service, Sir Charles Gairdner Hospital, Perth, Australia; ²Department of Physiotherapy, Sir Charles Gairdner Hospital, Perth, Australia; ³Dietetics and Nutrition, Sir Charles Gairdner Hospital, Perth, Australia; ⁴Medical School, University of Western Australia, Perth, Australia; ⁵Department of Medical Imaging, Fiona Stanley Hospital, Perth, Australia; ⁶Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Perth, Australia; ⁷School of Human Sciences, University of Western Australia, Perth, Australia; ⁸West Australian Sleep Disorders Research Institute, QEII Medical Centre, Perth, Australia; ⁹Department of Transplant Surgery, Sir Charles Gairdner Hospital, Perth, Australia

Background and Aims: In liver transplantation (LT) candidates, sarcopenia has been associated with increased waitlist and post-transplant mortality. This may limit access to LT in these patients. Skeletal muscle index (SMI), measured by cross-sectional imaging, is an objective, reproducible measure of sarcopenia, but does not encompass muscle function. Performance-based tests of muscle function and cardiopulmonary exercise test (CPET) are objective assessments of functional status. The relationship between sarcopenia and measures of functional status is poorly characterized in this cohort of patients. We aimed to evaluate the association between SMI and measures of muscle function, and to assess LT outcomes in patients with sarcopenia and physical frailty.

Methods: Retrospective data was collected from a single-centre database of cirrhotic patients who underwent workup for LT in Australia from January 2019 to September 2023. Patients underwent physiotherapy and nutrition assessments prior to being waitlisted and received individualized exercise and nutritional interventions up to the time of transplant or delisting. SMI was calculated at the time of workup, from axial CT abdomen slices at L3 vertebral level using automated software. Cutoffs for sarcopenia were SMI <50 cm²/m² in men and <39 cm²/m² in women. Data was collected from performance-based tests of muscle function: hand grip strength (HGS), 30-second Chair Stand Test (30sCST), six-minute walk distance (6MWD), and Liver Frailty Index (LFI) score. Anaerobic threshold (AT), peak oxygen uptake (VO2peak) and peak work (Wpeak) were collected from CPET. Data was analysed using SPSS.

Results: 120 patients were included: 68% males, mean age 53.9±11.4 years, mean MELD 15.8±7. Mean SMI was 47.1±7.3 cm²/m² in males and 37.7±6.3 cm²/m² in females and 60% of all patients were sarcopenic. Using Spearman’s correlation analysis, SMI was significantly correlated with BMI (r_s=0.513, p<0.001), HGS (r_s=0.538, p<0.001), 30sCST (r_s=0.263, p=0.005), LFI score (r_s=-0.319, p=0.001), AT (r_s=0.278, p=0.021), VO2peak (r_s=0.245, p=0.042) and Wpeak (r_s=0.460, p<0.001), but not 6MWD (r_s=0.164,p=0.086). Sarcopenia, as a categorical variable, correlated with BMI (r_s=-0.452, p<0.001), 30sCST (r_s=-0.215, p=0.023), LFI score (r_s=0.234 p=0.013), but not with 6MWD, HGS, AT, VO2peak or Wpeak. At the time of data collection, 85 (71%) patients were waitlisted, and 64 (53%) were transplanted. SMI was significantly lower in patients who were delisted due to deterioration in liver disease (37.5±6.1 cm²/m²) compared to patients who underwent transplantation (44.9±8.7cm²/m²), p= 0.023. There was a trend towards frailty in patients who were delisted (mean LFI 4.2±0.4) compared with those who were transplanted (3.7±0.6), p=0.062. Of the 64 transplanted patients, 57.8% were sarcopenic. Mean follow up post-transplant was 22 months (range 1-53 months). KM survival at 1 and 3 years was 91% and 87% for sarcopenic patients, compared with 92% and 85% in non-sarcopenic patients, p=0.612. There was no difference between sarcopenic vs non-sarcopenic patients in the length of post-operative ICU stay (p=0.274) or post-operative inpatient stay (p=0.478). Post transplant survival for frail patients (LFI>4.5, n=9) was 100% at 1 and 3 years, compared to non-frail patients, which was 90% and 83% respectively, p=0.182.

Conclusion: SMI correlated with tests of muscle function and CPET. Sarcopenic patients can have successful liver transplant outcomes with personalised physiotherapy and nutritional interventions. Prioritisation of patients with lower SMI may help reduce waitlist mortality. Further studies are required to validate these findings.

290

Analysis of the impact of female sex and sarcopenia on serum creatinine and waitlist priority for liver transplantation

Shivangi Gupta¹, Angus W Jeffrey¹, Zhengyi Wang^1,2, Leon A Adams^1,2, George Garas¹, Gerry MacQuillan¹, Michael Wallace¹, Briohny Smith¹, Wai Lim³, Roslyn Francis^2,4, Christopher Welman⁵ and Gary P Jeffrey^1,2

¹Western Australian Liver Transplant Service, Sir Charles Gairdner Hospital, Perth, Australia; ²Medical School, University of Western Australia, Perth, Australia; ³Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia; ⁴Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Perth, Australia; ⁵Department of Medical Imaging, Fiona Stanley Hospital, Perth, Australia

Background and Aim: Serum creatinine (sCr) is a poor measure of renal function in patients with cirrhosis, particularly in the presence of sarcopenia. Model for End-Stage Liver Disease (MELD) score incorporates sCr and is used to prioritise those on the liver transplant waitlist. Females have a higher waitlist mortality rate which is proposed to be due to lower muscle mass and consequent lower sCr values in MELD scores. This study evaluated the difference between sCr and calculated creatinine (cCr) derived from the measured GFR (mGFR), in patients with cirrhosis. The effect of sex and sarcopenia was studied for bias.

Methods: Retrospective data was collected cirrhotic patients, from an Australian centre, who had workup for liver transplantation from 2019-2023. A control population was live renal donors with normal renal function (n=48). The CKD-EPI equation was rearranged to determine cCr as a function of mGFR. Underestimation of creatinine was calculated as the difference between cCr and sCr, and called delta creatinine (ΔCr). MELD, MELD-Na and MELD 3.0 scores were calculated using cCr and sCr; and the difference was delta MELD (ΔMELD). Skeletal muscle area was obtained from CT images at L3 vertebral level, using automated software, and adjusted for height to obtain skeletal muscle index (SMI, cm2/m2). Data analysis was performed using SPSS.

Results: 119 patients were included (32% females, 68% males; mean age 53.8±11.4yrs; mean mGFR 80.5± 28.6 ml/min/1.73m2, mean MELD 15.4±6.2). Mean MELD, MELD-Na and MELD 3.0 scores were significantly higher in females v males (p=0.009, p=0.008 and p<0.001 respectively). 64.2% of males (SMI<50 cm2/m2 ) and 52.6% of females (SMI< 39 cm2/m2) were sarcopenic, p=0.236. In the study group, the mean cCr (110.6±53.7μmol/L) was significantly higher than mean sCr (80.5±45.8μmol/L), p<.001. In the controls, mean cCr (78.7±24.6μmol/L) was not significantly different to mean sCr (73.0±13.2μmol/L), p=.115. There was no significant difference in the ΔCr between males and females in the study group (males, 27.6±43.0μmol/L; females 35.2±55.2μmol/L, p=.720) or control group (males 7.4±21.8μmol/L; females 4.3±27.4mol/L, p=0.416). In the study group, SMI was inversely associated with ΔCr, p=.023. Multivariate analysis using age, sex, SMI, INR, bilirubin and sodium values, found SMI and bilirubin were independently associated with ΔCr (p=0.022 and p=0.020 respectively). ΔCr was higher in sarcopenic patients (35.6±48.4μmol/L) compared to non-sarcopenic patients (21.4±44.3μmol/L), but not statistically significant (p=.113). Mean cCr-MELD (17.0±6.8) was more than sCr-MELD (15.4±6.3), p<.001. There was no significant difference between males and females for ΔMELD (p=.801), ΔMELD-Na (p=0.819) or ΔMELD3.0 (p=.616). Multivariate analysis using SMI and sex found SMI was independently associated with ΔMELD (p=0.015), ΔMELD-Na (p=.025) and ΔMELD 3.0 (p=.016). Sarcopenic patients had higher ΔMELD (p=.020), ΔMELD-Na (p=.037) and ΔMELD3.0 (p=.015). Subgroup analysis in patients with GFR ≤60ml/min/1.73m2 (n=36) showed no difference between the ΔCr or ΔMELD of males (26.3±51.8μmol/L, 2.3±2.2) and females (29.1±16.7 μmol/L,1.8±1.2), p=.834 and p=.384. Sarcopenic patients had a higher ΔCr (36.1±19.1μmol/L) and ΔMELD (2.5±1.4) compared with non-sarcopenic patients (ΔCr, 10.5±59.7μmol/L, p=.060; ΔMELD, 1.1±2.1, p=.020). Multivariate analysis using sex and sarcopenia found that sarcopenia was independently associated with ΔCr (p=.046) and ΔMELD (p=.032).

Conclusion: Sex did not impact ΔCr or ΔMELD. SMI was independently associated with ΔCr and ΔMELD. The higher waitlist mortality seen in females is unlikely due to lower serum creatinine, and other factors need to be further investigated.

295

Different patterns of care and survival outcomes in transplant-centre managed patients with early-stage HCC: Real-world data from an Australian multi-centre cohort study

Jonathan Abdelmalak^1,2,3, Simone Strasser⁴, Natalie Ngu⁴, Claude Dennis⁴, Marie Sinclair³, Avik Majumdar³, Kate Collins³, Katherine Bateman³, Anouk Dev⁵, Joshua Abasszade⁵, Zina Valaydon⁶, Daniel Saitta⁶, Kathryn Gazelakis⁶, Susan Byers⁶, Jacinta Holmes^7,8, Alexander Thompson^7,8, Dhivya Pandiaraja⁷, Steven Bollipo⁹, Suresh Sharma⁹, Merlyn Joseph⁹, Rohit Sawhney^10,11, Amanda Nicoll^10,11, Nicholas Batt¹⁰, Myo Jin Tang¹, Stephen Riordan¹², Nicholas Hannah¹³, James Haridy¹³, Siddharth Sood¹³, Eileen Lam², Elysia Greenhill², John Lubel^1,2, William Kemp^1,2, Ammar Majeed^1,2, John Zalcberg^14,15 and Stuart Roberts^1,2

¹Department of Gastroenterology, Alfred Hospital, Melbourne, Australia; ²Monash University, Melbourne, Australia; ³Austin Hospital, Heidelberg, Australia; ⁴Royal Prince Alfred Hospital, Camperdown, Australia; ⁵Monash Health, Clayton, Australia; ⁶Western Health, Footscray, Australia; ⁷St Vincent's Hospital Melbourne, Fitzroy, Australia; ⁸University of Melbourne, Parkville, Australia; ⁹John Hunter Hospital, New Lambton Heights, Australia; ¹⁰Box Hill Hospital, Box Hill, Australia; ¹¹Eastern Health Clinical School, Box Hill, Australia; ¹²Prince of Wales Hospital, Randwick, Australia; ¹³Royal Melbourne Hospital, Parkville, Australia; ¹⁴School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia; ¹⁵Department of Medical Oncology, Alfred Hospital, Melbourne, Australia

Background and Aim: Management of early-stage hepatocellular carcinoma (HCC) is complex with multiple treatment strategies available. There is a paucity of literature regarding variation in patterns of care and outcomes between transplant and non-transplant centres. We performed this real-world multi-centre cohort study in two liver transplant centres (LTCs) and eight non-transplant centres (NTCs) across Australia to assess for variation in patterns of care and key survival outcomes.

Methods: Patients with Barcelona Clinic Liver Cancer (BCLC) 0/A HCC, first diagnosed between 01/01/2016 and 31/12/2020 who were managed at a participating site were included in the study. Patients were excluded if they had a history of prior HCC or if they received upfront liver transplantation.

Results: A total of 887 patients were included in the study, with 433 patients managed at a LTC and 454 patients managed at NTC. Management at a LTC did not significantly predict allocation to resection using multivariable binary logistic regression adjusting for tumour burden as well as age, gender, liver disease aetiology, liver disease severity and medical comorbidities (adjusted OR 0.75 95%CI 0.50 to 1.11, p=0.148). However, in those not receiving resection, LTC and NTC patients were systematically managed differently, with LTC patients five times less likely to receive upfront ablation than NTC patients (adjusted OR 0.19, 95%CI 0.13 to 0.28, p<0.001). LTC patients had significantly higher proportions of patients undergoing TACE for every tumour burden category, including those with single tumour 2cm or less (p<0.001). 42 of 887 patients (4.7%) underwent transplantation during follow-up, with higher Charlson Comorbidity Index (CCI) in LTC patients who received liver transplant compared to NTC patients (median 5 vs 3, p=0.028). Using multivariable Cox-proportional hazards analysis, management at a transplant centre was associated with reduced all-cause mortality (adjusted HR 0.71, 95%CI 0.51 to 0.98, p=0.036) and competing-risk regression analysis considering liver transplant as a competing event demonstrated a similar reduction in risk (adjusted HR 0.70., 95% CI 0.50 to 0.99, p=0.041), suggesting that the reduced risk of death is not fully explained by higher rates of transplantation.

Conclusion: Our study highlights systematic differences in HCC care and survival outcomes between large volume liver transplant centres and other sites, which has not previously been well-described. Further work is needed to prospectively evaluate the differences in treatment strategy, access to transplantation and long-term survival outcomes both within and across centres in order to minimise unwarranted treatment variation and maximise patient outcomes across Australia.

298

Improved survival outcomes with surgical resection compared to ablative therapy in early-stage HCC: A large, real-world, propensity-matched, multi-centre, Australian cohort study

Jonathan Abdelmalak^1,2, Simone Strasser³, Natalie Ngu³, Claude Dennis³, Marie Sinclair⁴, Avik Majumdar⁴, Kate Collins⁴, Katherine Bateman⁴, Anouk Dev⁵, Joshua Abasszade⁵, Zina Valaydon⁶, Daniel Saitta⁶, Kathryn Gazelakis⁶, Susan Byers⁶, Jacinta Holmes^7,8, Alexander Thompson^7,8, Dhivya Pandiaraja⁷, Steven Bollipo⁹, Suresh Sharma⁹, Merlyn Joseph⁹, Rohit Sawhney^10,11, Amanda Nicoll^10,11, Nicholas Batt¹⁰, Myo Jin Tang¹, Stephen Riordan¹², Nicholas Hannah¹³, James Haridy¹³, Siddharth Sood¹³, Eileen Lam^2,14, Elysia Greenhill^2,14, John Lubel^1,2, William Kemp^1,2, Ammar Majeed^1,2, John Zalcberg^14,15 and Stuart Roberts^1,2

¹Alfred Hospital, Melbourne, Australia; ²Monash University, Melbourne, Australia; ³Royal Prince Alfred Hospital, Sydney, Australia; ⁴Austin Hospital, Melbourne, Australia; ⁵Monash Health, Melbourne, Australia; ⁶Western Health, Melbourne, Australia; ⁷St Vincent's Hospital Melbourne, Melbourne, Australia; ⁸University of Melbourne, Melbourne, Australia; ⁹John Hunter Hospital, Newcastle, Australia; ¹⁰Eastern Health, Melbourne, Australia; ¹¹Eastern Health Clinical School, Monash University, Melbourne, Australia; ¹²Prince of Wales Hospital, Sydney, Australia; ¹³Royal Melbourne Hospital, Melbourne, Australia; ¹⁴School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia; ¹⁵Department of Medical Oncology, Alfred Hospital, Melbourne, Australia

Background and Aim: The optimal treatment approach in very-early and early-stage hepatocellular carcinoma (HCC) is not precisely defined, with ambiguity in the literature around the comparative efficacy of surgical resection versus ablation as curative therapies for limited disease. We performed this real-world propensity-matched, multi-centre cohort study to assess for differences in survival outcomes between those undergoing resection and those receiving ablation.

Methods: Patients with Barcelona Clinic Liver Cancer (BCLC) 0/A HCC first diagnosed between 01/01/2016 and 31/12/2020 who received ablation or resection as initial treatment were included in the study.

Results: A total of 450 patients were included in the study from 10 major liver centres including two transplant centres. Patients who underwent resection were systematically different to those who received ablation, with significant differences seen in age, managing centre, liver disease aetiology, diabetes, platelet count, Charlson Comorbidity Index (CCI) tumour burden and Child Pugh score, Propensity-score matching was performed using key covariates producing 156 patients available for analysis with 78 in each group. Over a median follow up of 53.3 months, patients who underwent resection had significantly improved overall survival (97.4% vs 88.5%, log-rank test p=0.023) with similar results in the original unmatched cohort (94.9% vs 83.9%, log-rank test p<0.001). Local recurrence-free survival was superior in the resection group (88.5% vs 76.7%, log-rank test p=0.027) over a median follow-up of 37.9 months with similar superior 3-year recurrence-free survival (75.6% vs 57.5%, log-rank test p=0.007). Major complication rate was low in the original unmatched resection group who had been selected for surgery by a real-world multidisciplinary group of expert clinicians (2 out of 196, 1.0%).

Conclusion: Our study suggests that surgical resection results in more durable local tumour control in BCLC 0/A HCC as compared to ablation which translates to improved survival outcomes. Based on real-world data, our study supports the use of surgical resection in preference to ablation as first line curative therapy where possible in appropriately selected BCLC 0/A HCC patients.

299

Management of muscle cramps in patients with cirrhosis: a systematic review of randomised controlled trials

Andrew Roberts¹, Joseph Makar², Jonathan Abdelmalak³, Marie Sinclair⁴, Adam Testro⁴ and Avik Majumdar⁴

¹The Royal Melbourne Hospital, Melbourne, Australia; ²The University of Melbourne, Melbourne, Australia; ³The Alfred, Melbourne, Australia; ⁴Austin Health, Melbourne, Australia

Background: Muscle cramps are common in patients with cirrhosis. Despite their prevalence and impact on health-related quality of life, there are no widely used clinical practice guidelines for management of muscle cramps in cirrhosis. The aim of this review was to critically evaluate current evidence regarding treatment of muscle cramps in cirrhosis.

Methods: A systematic review using PubMed Central, MEDLINE, Embase, and Scopus databases was performed by two independent reviewers to identify randomized controlled trials (RCTs) reporting interventions for muscle cramps in cirrhotic patients.

Results: Eleven RCTs evaluating eleven distinct interventions were identified. Baclofen, methocarbamol, orphenadrine, and taurine reduced cramp frequency, severity, and duration when compared to placebo. Human albumin, pregabalin, and quinidine reduced cramp frequency compared to placebo. Pickle juice reduced cramp severity compared to placebo. BCAAs and calcium carbonate were found to reduce cramp frequency. Electro-acupuncture was the only intervention which demonstrated no significant therapeutic effect. Pregabalin was the only agent associated with significant side effects that limited its use.

Conclusion: Baclofen, BCAAs, methocarbamol, orphenadrine, pickle juice, and taurine are all recommended treatments, with evidence for their efficacy and safety. The other agents cannot be recommended for use based on current available evidence. Further work is needed to validate the use of these treatments in different populations and investigate comparative safety and efficacy as well as therapeutic strategy.

302

Unmet supportive care needs among patients with cirrhosis – need for a patient centric approach

Osamah Al-obaidi, Alice Lee, Emily He, Peck Pogoy, Megan Day and Karen Waller

Concord Hospital, Concord, Australia

Background and Aim: Cirrhosis is associated with many symptoms that can impact quality of life (QOL). Despite their importance, patient reported measures are rarely collected in the outpatient setting, as they are time-intensive to administer. This study aimed to describe the symptom burden among patients with cirrhosis at a single centre, to understand differences in supportive care needs among our patients and to inform improvements in service delivery to reduce patient morbidity.

Methods: We included inpatients and outpatients with cirrhosis at Concord Repatriation General Hospital. Patients were asked to complete the Supportive Needs Assessment (SNAC) tool, a QOL questionnaire. Responses to each item are scored on a 5-point scale: 0 indicates no unmet needs and 5 indicates the highest level of unmet needs. Items are categorised into four subscales: lifestyle needs, physical needs, informational needs and psychosocial needs. Patients were grouped into those with unmet needs and low/no needs. For each patient, the overall SNAC score and each subscale score was calculated. The proportion of patients with unmet needs were reported by clinical characteristics and compared using Chi-square test. Differences in mean SNAC scores were compared using student T-test.

Results: Between July 2022 to April 2024, 34 patients completed the SNAC tool: most were men (59%), aged 60 or over (59%), spoke English as primary language (85%), were not employed (53%) and did not live alone (71%). Most patients had Child Pugh A cirrhosis (50%), with primary aetiologies alcohol-related liver disease (ARLD, 44%), followed by metabolic dysfunction-associated fatty liver disease (MAFLD, 29%) then viral hepatitis (26%) Most (29, 85%) had unmet needs, and few (5, 15%) had no/low needs. Among patients with unmet needs, the highest subscale was physical needs (89.7%) followed by informational needs (82.8%), psychosocial (79.3%) and lifestyle (55.2%). All patients with MAFLD (10/10, 100%) had unmet needs, vs 14/15 (93%) with ARLD and 5/9 (56%) with viral hepatitis (p=.019). The mean SNAC score for patients with ARLD was 1.9 (SD=0.9) and for patients with MAFLD was 1.6 (SD=0.7); both scores were significantly higher than patients with viral hepatitis (mean 0.8, SD=0.6, p = 0.003 and 0.017 respectively).

Conclusion: The vast majority of patients with cirrhosis in our centre have unmet needs, with needs higher among those with steatotic liver disease than underlying viral hepatitis. Based on study results, increased services should address physical and informational needs.

317

Screening emergency admissions at risk of chronic hepatitis 3 extension (SEARCH 3X) - universal is better than risk-based screening for viral hepatitis

Basheer Alshiwanna^1,2,3,8, Miriam Tania Levy^1,2,3, Julia Di Girolamo^2,3, Melissa Bagatella¹, Irena Petrovski⁴, Robert Porritt¹, David Thomas¹, Shahida Bakridi¹, Hung Tran⁵, Sophie Gryllis¹, Maria Tiglao⁵, Rebecca Haack⁴, Kristian Peralta⁴, Julie Doan¹, Jeremy Lawrence⁶, Richard Cracknell⁴, Michael Maley¹, Hong Foo¹, Nathan Jones⁴, Gregory J Dore^3,7 and David Prince^1,3

¹Liverpool Hospital, Sydney, Australia; ²Ingham Institute for Applied Medical Research, Sydney, Australia; ³The University of New South Wales, Sydney, Australia; ⁴Campbelltown Hospital, Sydney, Australia; ⁵NSW Health Pathology IT Services, Sydney, Australia; ⁶Fairfield Hospital, Sydney, Australia; ⁷The Kirby Institute, Sydney, Australia; ⁸The Canberra Hospital, Canberra, Australia

Background and Aim: Viral hepatitis remains an important public health concern globally. Despite effective therapies for cure of hepatitis C (HCV) and suppression of hepatitis B (HBV), a significant proportion of Australians remain undiagnosed or not linked with care. We evaluate the use of universal, automated hepatitis screening in the emergency department (ED) and assess diagnosis rates and linkage to care (LTC) success.

Methods: A novel pilot clinical service utilizing automated universal hepatitis screening in the ED, “SEARCH 3X” (Screening of Emergency Admissions at Risk of Chronic Hepatitis Third Extension) was implemented across two metropolitan hospitals in Sydney, Australia. A computer algorithm solution automatically added Hepatitis B surface antigen (HBsAg) and Hepatitis C antibody (HCV Ab) tests when an adult underwent routine biochemistry testing in ED. Data was collected on patient demographics, overall prevalence of viral hepatitis and effectiveness of LTC (defined as successful contact by the SEARCH team).

Results: 10,204 unique patients were tested using the SEARCH 3X algorithm. Positive serology for HBsAg and/or HCV Ab was detected in 92 (0.9%) and 170 (1.7%) patients respectively, equating to 259 (2.5%) unique patients overall (3 with HBV-HCV co-infection). The median age of the population tested was 58 years old (IQR 45-66), with a relatively even gender distribution (M:F; 44%:56%). The prevalence of positive HBsAg and/or HCV Ab in Indigenous Australians was 8.0% (3 HBV and 28 HCV from 375 tested), in non-indigenous Australians 1.9% (6 HBV and 79 HCV from 4384 tested), and in Overseas-born (OB) patients 2.7% (83 HBV and 63 HCV from 5445 tested). Of the 259 total positive patients, 251 were eligible for follow-up (too unwell n = 5, deceased n = 3) and 224 (86%) were successfully LTC. HCV diagnosis was new in 16/170 (9%) patients. HCV Ab positive patients were more often male (62% vs 44%; p<0.001) and Indigenous (16.5% vs 3.5%; p<0.001) compared with HCV Ab negative patients. HCV RNA was available in 134/170 HCV patients. RNA test was positive in 16 patients (12%) and negative in 118 (88%). Of RNA negative patients, 77/118 (65%) had previous HCV treatment, 28/118 (24%) had no previous treatment but had a risk factor for blood-borne virus; 13/118 (11%) treatment status and/or risk factor unknown. HBV diagnosis was new in 23/92 (25%) patients. Of those with known diagnosis, only 24/69 (39%) were receiving guideline-based care. HBsAg positive patients were more often OB (90% vs 53%; p<0.001) and non-English speaking (39% vs 15%; p<0.001) compared to HBsAg negative patients.

321

Hepatitis C treatment with a direct-acting antiviral and concurrent carbamazepine: A case report

Li Ean Mah¹, Sheridan Rodda^1,2, Eliza Flanagan^2,3 and Michael Braude¹

¹Monash Health, Melbourne, Australia; ²Monash University, Melbourne, Australia; ³Barwon Health, Geelong, Australia

Introduction: Direct acting antiviral (DAA) therapies have revolutionised hepatitis C virus (HCV) management, however barriers to treatment exist. One such example is the complexity around co-administration of DAAs and carbamazepine. This combination is contraindicated as carbamazepine induces intestinal P-glycoprotein and CYP450, reducing DAA effectiveness and increasing risk of virological failure. Carbamazepine reduces the area under the curve of sofosbuvir, glecaprevir and pibrentasvir by approximately half. Many patients and practitioners are reluctant to change effective anti-seizure or mood-stabilising therapies, due to concerns over breakthrough seizures, mood swings or psychosis, and social ramifications such as temporary driving bans. Consequently, there is a subset of patients that have not received HCV treatment. We describe a patient treated with DAA therapy, while co-prescribed carbamazepine and outline future practical considerations.

Case report: A 57-year-old woman attended our multidisciplinary (medical, nursing, pharmacist, liver care navigator) hepatology clinic for assessment and management of chronic HCV infection. The patient was treatment-naïve from a HCV perspective, with normal liver function tests and viral load of 5.88 log10 IU/mL at baseline. The patient was non-cirrhotic with a FibroScan score of 9.5kPa. Medical history was relevant for bipolar disorder managed with controlled-release carbamazepine 600mg in the morning. Pharmacist-led review of clinical and medication history was conducted. At the time, the patient had no psychiatrist and did not wish to alter her current therapy. Literature review found published case reports describing successful treatment of Hepatitis C virus with interacting anti-epileptic medicines.^1-3 Upon multidisciplinary discussion, a 12-week course of sofosbuvir-velpatasvir concurrent with carbamazepine was prescribed, after a risk versus benefit discussion with the patient. The pharmacist provided education including strategies to encourage adherence, separation of the DAA dose from carbamazepine and taking the DAA after meals to maximise absorption. Carbamazepine levels were monitored throughout treatment, with no change from baseline levels (31 μmol/L). The patient achieved sustained virologic response, as evidence by a negative HCV load at 24 weeks after treatment completion.

Conclusion: The cohort of people remaining with HCV is challenging to identify and treat. Making changes to established anti-epileptic or mood stabilising medications can be difficult, potentially detrimental, and sometimes unavoidable. Expertise and collaboration within a multidisciplinary team can generate positive outcomes for complex patients with HCV. Clinicians should be aware of the emerging literature supporting co-administration of DAAs with interacting medicines in exceptional circumstances.

References

1. Braude, M et al. Hepatitis C virus treatment with glecaprevir and pibrentasvir in patients co-prescribed carbamazepine: Three case reports. World J Gastrointest Pharmacol Ther. 2023; 14(4): 33–38.

2. Natali, KM, Jimenez, HR, Slim, J. When Coadministration Cannot Be Avoided: Real World Experience of Direct Acting Antivirals for the Treatment of Hepatitis C Virus Infection in Patients on First Generation Anticonvulsants. J Pharm Pract. 2022; 35(3): 495-499. https://doi.org/10.1177/0897190020977762

3. Marcos-Fosch, C, et al. Anti-epileptic drugs and hepatitis C therapy: Real-world experience. J Hepatol 2021; 75(4): 984-985.

326

Exercise stress echocardiography is a feasible alternative to pharmacologic stress echocardiography for cardiac risk evaluation in patients with cirrhosis prior to liver transplantation

Madeleine Gill^1,2,3, Joanna Huang¹, Daniel Brieger⁴, Jessica Handreck², Fiona Fraser², Andrew Brodzeli², Imre Hunyor^1,2, Michele McGrady^1,2, Rachael Jacob^1,2, Talal Valliani¹, Ken Liu^1,2, David Bowen^1,2,3, Simone Strasser^1,2, Anoop Koshy^5,6, Geoffrey McCaughan^1,2,3 and Avik Majumdar^2,5,6

¹Royal Prince Alfred Hospital, Sydney, Australia; ²University of Sydney, Sydney, Australia; ³Centenary Institute, Sydney, Australia; ⁴Royal North Shore Hospital, Sydney, Australia; ⁵Austin Health, Melbourne, Australia; ⁶University of Melbourne, Melbourne, Australia

Background and Aim: Dobutamine stress echocardiography (DSE) is often used in preference to exercise stress echocardiography (ESE) for cardiac risk evaluation prior to liver transplantation (LT) due to perceived challenges in attaining adequate workload with ESE. This study aimed to determine the tolerability and ability of ESE to attain target heart rate (THR) compared to DSE.

Methods: A retrospective cohort study of consecutive patients with cirrhosis undergoing cardiac evaluation prior to LT at a state-wide transplant centre between 2010-2020 was performed. Choice of stress modality was at the clinician’s discretion. Treadmill ESE utilized Bruce protocol to maximum capacity. DSE utilized incremental dosing from 10-50mcg/kg, with hand grip and atropine to augment heart rate (HR) if required, according to standardized protocol. THR was defined as 85% of the maximum predicted HR (220-age). Functional capacity on ESE was assessed by metabolic equivalents (METs). Beta-blockers were withheld 72 hours prior to both DSE and ESE; patients inadvertently continuing were excluded from analysis.

Results: Overall, 452 patients were included. In our cohort, 169 (37%) underwent ESE. Model for end-stage liver disease (MELD) score was lower in ESE patients (ESE: 13; IQR, 9-17; vs DSE: 18; IQR, 15-22; P<0.001). Fewer patients undergoing ESE had ascites (24% vs 52%; P<0.001). More DSEs were prematurely ceased due to complications, mainly hypotension and arrhythmia, compared with ESE (8% vs 3%; P=0.04). THR was attained in 85 of 169 (50%) ESEs, compared with 91 of 283 (32%) DSEs (P<0.001). The median METs achieved on ESE were 7.0 (IQR, 5.4-9.8). Of the patients who did not attain THR on ESE, 43 (51%) achieved ≥7 METs and this was considered an adequate test at our institution. Similarly, on DSE, 121 (63%) achieved 80-84% of maximum predicted HR, also considered adequate. On multivariate logistic regression, DSE was an independent predictor of failure to attain THR, after adjusting for sex, age, hypertension, diabetes, ascites, hepatic encephalopathy and MELD (OR 1.82; 95% CI, 1.16-2.87, P=0.009). Additionally, moderate-to-severe ascites (OR 1.79; 95% CI, 1.04-3.10; P=0.037) and age (OR 1.04; 95% CI, 1.01-1.08; P=0.007; per unit increase in age) also predicted failure to attain THR in the overall cohort. For ESEs alone, the only independent predictor was MELD (OR 1.05; 95% CI, 1.00-1.11; P=0.048; per unit increase in MELD), and age for DSE (OR 0.95; 95% CI, 0.92 – 0.99; P=0.025; per year increase in age).

Conclusion: ESE was feasible in over a third of patients undergoing cardiac evaluation prior to LT. When compared to DSE, patients undergoing ESE were almost twice as likely to attain THR, although these patients had less severe liver disease. Given the higher complication rate observed during DSE, ESE may be considered as an alternative modality in selected individuals undergoing LT assessment.

332

Remaining chronic hepatitis C treatment gaps impact on the care cascade of HCV related hepatocellular carcinoma

Joan Ericka Flores¹, Alexander Thompson^1,2, Thai Hong^1,2, Stuart Roberts³, William Kemp³, Ammar Majeed³, Amanda Nicoll⁴, Rohit Sawhney⁴, Zina Valaydon⁵, Marno Ryan^1,2, Marie Sinclair⁶, Gauri Mishra⁷ and Jessica Howell^1,2

¹St Vincent's Hospital Melbourne, Fitzroy, Australia; ²University of Melbourne, Clayton, Australia; ³Alfred Health, Melbourne, Australia; ⁴Eastern Health, Box Hill, Australia; ⁵Western Health, Footscray, Australia; ⁶Austin Health, Heidelberg, Australia; ⁷Monash Health, Clayton, Australia

Background and Aim: Direct acting antivirals (DAAs) for chronic hepatitis C (HCV) were made universally available in Australia in 2016. The impact of HCV cure availability on the clinical presentation of HCV-related HCC (HCV-HCC) is not well described in Australia. In this study, we aimed to describe the cascade of HCV care in people with HCV-HCC. We also describe the impact of achieving SVR on HCC stage at diagnosis, treatment receipt and survival.

Methods: All incident HCC cases were retrospectively identified between 1st January 2018 to 31st December 2021 from six tertiary hospital networks in Melbourne and followed up to 31^st October 2023. HCC was diagnosed histopathologically or radiologically by LIRADS criteria with HCC multidisciplinary team (MDT) consensus. SVR confirmed by HCV RNA negativity on blood tests or EMR documentation. Bivariable analysis was conducted using Chi square and Wilcoxon rank-sum test, and Cox multivariable regression models determined factors associated with overall survival.

Results: A total of 1013 incident cases of HCC were diagnosed, of these 35% (n=348) were due to HCV. There was a male predominance (80%, n=279) and median age of 61 years (IQR 57, 65) among those with HCV-HCC: significantly younger than non-HCV-HCC cases (median age 70 years IQR 63, 76.5 (p<0.0001). Cirrhosis was present in 95% (331/348) of HCV-HCC cases compared to 77% (509/665) non-HCV-HCC (p<0.0001); of these, 72% (238/331) had known cirrhosis compared to 60% (305/509), respectively (p<0.0001). More HCV-HCC cases had at least one surveillance scan in the 12 months preceding HCC diagnosis (45%, 158/348 vs 37%, 248/665) (p=0.012). There were no significant differences between HCV-HCC and non-HCV cases with respect to: proportions of early BCLC (51%, 175/348 vs 46%,306/665) (p=0.162), timely review in MDT within 2 weeks following referral (73% 236/325 vs 68% 414/610; p=0.133), timely treatment receipt within 4 weeks (32%, 105/329 vs 29%, 182/623; p=0.388) and proportion that received first line curative therapies (35%, 120/348 vs 31%, 203/665; p=0.199). SVR data were available for 98% (341/348): 61% with HCV-HCC (208/341) had achieved SVR from antiviral treatment with median time to HCC diagnosis from documented SVR of 1043 days (IQR 574, 1532). SVR was associated with a lower proportion of documented previous/current: intravenous drug use (26%, 54/208 vs 41%, 55/133; p = 0.003) and alcohol misuse (27%, 56/204 vs 43%, 57/133; p=0.003). 8%(18/208) with SVR had not been assessed as having cirrhosis prior to HCC diagnosis, 11 of whom had additional risk factors for cirrhosis. Significantly more cases with SVR had at least one surveillance scan in the year prior to HCC diagnosis (64% 133/208 vs 18%, 24/133; p<0.001); however, 36% (75/208) with SVR had no surveillance scans in the preceding 12 months. More HCV-HCC cases with SVR had early BCLC stage (59%, 122/208 vs 40%, 52/130) (p=0.001) and first line curative therapy (40%, 83/208 vs 27%, 27/133) (p=0.015). Where documented, fewer deaths occurred in individuals with SVR (42%, 74/178 vs 59%, 67/114; p=0.004) and median time to death following HCC diagnosis in the SVR group was 11.9 months (IQR 5.3, 21.4) compared to 6.0 months (IQR 2.7, 15.7) (p=0.02). SVR was associated with greater survival post HCC diagnosis (log rank HR 0.57; 95% CI 0.41-0.79; p=0.001), however this association did not remain significant when adjusted for age, Child Pugh class, diagnosis through surveillance and early BCLC stage disease at diagnosis (aHR 0.79, 95% CI 0.54-1.15 p=0.22).

Conclusion: Despite widespread availability of DAAs, a significant proportion of people with HCV-HCC remain untreated, have not been evaluated for cirrhosis and have not been enrolled in surveillance. Greater investment in health promotion and education to identify patients with HCV, increase uptake of liver fibrosis assessment and retention in specialist care and HCC surveillance is urgently needed to improve outcomes and reduce deaths from HCV-HCC.

336

Beyond the biopsy: Unraveling a rare cause of cholestasis

Nicholas Smith, Gandhi Arjun, Nivene Saad, Jennifer Borowsky and James Thomas

Princess Alexandra Hospital, Brisbane, Australia

Introduction: Hepatocyte nuclear factor 1-Beta (HNF1B) is a transcription factor of critical importance during the embryonic development of specialised epithelial tissues across various organ systems. Mutations in the HNF1B gene can lead to a spectrum of clinical manifestations including hepatic abnormalities.

Case report: A 25-year-old male was referred for evaluation of cholestatic liver enzymes. These were noted 3-years prior when diagnosed with diabetes mellitus. Apart from insulin and long term use of escitalopram for depression, there was no other medication or supplement use. There was no family history of liver disease. His BMI was 20.8mg/m2 with normal clinical examination. Laboratory results showed an alkaline phosphatase 342U/L, gamma-glutamyltransferase 236U/L, aspartate aminotransferase 29U/L, alanine aminotransferase 58U/L and total bilirubin 10mg/dl. Routine serological evaluation including for viral hepatitis and autoantibodies were also non-contributory. Median liver stiffness by transient elastography was 7.0kPa. Ultrasound and computer tomography showed an unremarkable liver. Magnetic resonance cholangiopancreatography did not reveal biliary abnormality though detected dorsal pancreatic agenesis and renal cysts (Figure 1). Liver biopsy was therefore undertaken and showed normal liver histology. Next generation gene sequencing revealed a heterozygous pathogenic variant confirming a diagnosis HNF1B deficiency.

Conclusion: HNF1B is involved in functional regulation of hepatic, biliary, kidney, brain, parathyroid and pancreatic B-cells [1]. HNF1B deficiency is the most frequent monogenic cause of developmental renal disease. Diabetes mellitus is the most common extra-renal phenotype. Other associations include electrolyte abnormalities, genitourinary malformation and an emerging link with neurodevelopmental disorders. The phenotypic range also includes pancreatic hypoplasia and hepatobiliary abnormalities [1]. Though inherited in an autosomal dominant manner, up to 50% of mutations are de novo. [1] There is a paucity of information regarding the hepatobiliary consequences of human HNF1B deficiency. A cholestatic liver enzyme pattern has been reported with variable histological manifestations from normal to a reduction in interlobular bile ducts with marked cholestasis and periportal fibrosis [2]. Electron microscopy has revealed a primary ciliary abnormality on biliary epithelia potentially explaining cholestasis [3]. The presence of normal routine serology, hepatobiliary imaging and histology highlights the diagnostic challenge of this condition. Until recently, making this genetic diagnosis was outside the scope of routine practice. Advances in genetic sequencing technology have been followed by gains in chemistry, cost-effectiveness and thus access. The judicious use of next-generation sequencing can improve our diagnostic capability and thus, recognition of such diseases in turn improving our understanding of their epidemiology, biology and clinical management.

References

1. Kotalova, R, Dusatkova, P, Cinek, O, Dusatkova, L, Dedic, T, Seeman, T, Lebl, J, Pruhova, S. Hepatic phenotypes of HNF1B gene mutations: a case of neonatal cholestasis requiring portoenterostomy and literature review. World J Gastroenterol. 2015 Feb 28; 21(8): 2550-7.

2. Gambella, A, Kalantari, S, Cadamuro, M, Quaglia, M, Delvecchio, M, Fabris, L, Pinon, M. The Landscape of HNF1B Deficiency: A Syndrome Not Yet Fully Explored. Cells. 2023 Jan 13; 12(2): 307.

3. Roelandt, P, Antoniou, A, Libbrecht, L, Van Steenbergen, W, Laleman, W, Verslype, C, et al. HNF1B deficiency causes ciliary defects in human cholangiocytes. Hepatology 2012; 56(3): 1178–1181.

339

Comparison of liver stiffness using two-dimensional shear wave elastography and transient elastography (FibroScan®) methods: focus on the accuracy in diagnosis of fibrosis and cirrhosis

Kathryn Sharley¹, Matthew Le¹, MaryAnn King¹, Meegan Gun¹, Anton Colman¹, Kathy Pietris¹, Olga Sukocheva¹ and Edmund Tse^1,2

¹Royal Adelaide Hospital, Adelaide, Australia; ²School of Medicine, University of Adelaide, Adelaide, Australia

Background and Aim: Non-invasive assessment of liver fibrosis is crucial in chronic liver disease management. Transient elastography (TE, FibroScan®) is current standard of care for assessment of cirrhosis and clinically significant portal hypertension (CSPH) using Baveno criteria. The use of TE is limited by current funding models and hence two-dimensional shear wave elastography (SWE) as a measure of liver stiffness during routine abdominal ultrasound (US) may be a suitable alternative. This study aims to compare SWE and TE results and to identify sub-groups where it may be less reliable.

Methods: This is a single-centre retrospective study from a tertiary teaching hospital. Between June 2023 and April 2024, sixty outpatients had an abdominal US with SWE and a recent TE. Median liver stiffness results from the two modalities were compared to determine correlation and further sub-group analyses were performed. Analysis was conducted using Spearman’s correlation test and SPSS tool (version 27, USA). The METAVIR (Meta-analysis of Histological Data in Viral Hepatitis) fibrosis score was calculated and compared for concordance. Parameters which may have affected concordance were reviewed, including body mass index (BMI), severity of steatosis and aetiology.

Results: There was significant correlation between the results of median liver stiffness recorded from SWE and TE (r = 0.683, p < 0.001) (Table 1). This correlation remained significant when assessing patients with minimal and severe steatosis (CAP <248 dB/m (r = 0.539, p = 0.010) and CAP > 280 dB/m (r = 0.800, p < 0.001) respectively) and in obese (BMI>30) patients (r = 0.568, p = 0.027). The METAVIR fibrosis score was the same between modalities in 63% and discordant of two or more stages of fibrosis in 10% of patients with fibrosis predominantly under-estimated by SWE. There was underdiagnosis of CSPH from SWE results compared to TE results in all patents who met Baveno criteria for diagnosis (17% of total cohort) (Table 2).

Conclusion: SWE has excellent concordance in assessment of liver fibrosis to TE overall. Results become discordant in patients with advanced fibrosis on TE and concerningly, SWE did not correlate with TE in the diagnosis of CSPH risking underdiagnosis with this modality.

341

Impact of direct acting antiviral therapy availability on hospital admissions and outcomes in gastro-oesophageal variceal haemorrhage

Shoko Satake¹, Benjamin Ngoi^1,2, Kathryn Sharley¹ and Edmund Tse^1,2

¹Royal Adelaide Hospital, Adelaide, Australia; ²School of Medicine, University of Adelaide, Adelaide, Australia

Background and Aim: Gastro-oesophageal varices (GEV) are a common complication of cirrhosis with haemorrhage leading to substantial mortality. Chronic hepatitis C (CHC) is a leading cause of cirrhosis and to address this, in March 2016 direct acting antiviral therapy (DAAs) were made widely available to Australians through the Pharmaceutical Benefits Scheme (PBS). We aimed to assess the real-world impact that this event had on acute variceal bleeds and their outcomes.

Methods: All patients who presented to our tertiary centre with a GEVH and proceeded to endoscopy between March 2011 and March 2021 were included. Patients were identified through the endoscopy database. Endoscopy findings, demographic and medical data were collected. Patients were divided into pre-DAA (March 2011-Feb 2016) and post-DAA groups (March 2016-Feb 2021) and compared using chi-squared, Student’s t-test or Mann-Whitney U testing.

Results: 290 presentations from 216 patients were included in the study. 79 (27.24%) had CHC and 141 (48.62%) presented pre-Feb 2016. Overall, 73% were male with an average age of 55.5 years (26-87). Most patients were either Child Pugh B (37.9%) or C (36.6%) on with an average MELD-NA of 17.6 (6-55). Demographics were similar between the two groups. The number of admissions were similar in the five years pre and post DAAs (n=149 vs n=141). Although there was a trend towards fewer annual cases since 2016. Alcoholic liver disease (ALD) was the most prevalent cause of cirrhosis (47%) followed by CHC (27%). CHC was more prevalent in the pre-DAA group (32.89% vs 21.28% p=0.0037) (Table 1). There was a greater incidence of hepatocellular carcinoma (HCC) in CHC patients compared to non CHC patients (25.32% vs 9.69% p <0.0001). CHC related HCC was similar in the pre and post DAA groups (26% vs 33%). Rates of hepatic encephalopathy (19.8% vs 17.3% p =0.86) and spontaneous bacterial peritonitis (2.5% vs 4.3% p =-0.733) were similar. Overall, 6-week mortality was 11.72% (Table 2). Although higher in the pre-DAA cohort, this was not statistically significant (13.42% vs 9.93%, p=0.37). 90-day mortality was higher in the CHC cohort (25.32% vs 17.24% p=0.0353) with the effect sustained up until 12 months.

Conclusion: Since DAAs have become widely available, the number of patients with CHC presenting with variceal haemorrhage has reduced. Mortality was higher in CHC patients, particularly at 90-days and may reflect the higher rates of HCC seen in this population.

342

Fibroscan-based screening to determine the prevalence and severity of metabolic-dysfunction associated steatotic liver disease in diabetes in a quaternary hospital

Janakan Selvarajah¹, Spiros Fourlanos^2,3, Weilun Gao¹ and Ashok Raj¹

¹Department of Gastroenterology, Royal Melbourne Hospital, Melbourne, Australia; ²Department of Endocrinology, Royal Melbourne Hospital, Melbourne, Australia; ³Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia

Background and Aim: Type 2 Diabetes (T2D) and obesity are the strongest risk factors for the development of Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD). The prevalence of MASLD is estimated to be 30-70% in T2D and 22% in adults with type 1 Diabetes (T1D), however recognition even in hospital clinics remains low. Fibroscan based Controlled Attenuation Parameter (CAP) is more sensitive than ultrasound for detecting steatosis. There are minimal published data in populations with diabetes in Australia using Fibroscan to screen for MASLD. We aimed to determine the prevalence and severity of MASLD in a clinic population with diabetes using Fibroscan screening, compared to documentation in clinical records. Secondary aims were to determine baseline and clinical factors associated with MASLD and significant fibrosis, and the sensitivity of non-invasive blood markers for screening for significant fibrosis.

Methods: Inpatient and outpatient presentations of diabetes patients at a large quaternary centre were retrospectively assessed (from January 2010 to December 2023 and August 2020 to December 2023 respectively) for a concurrent diagnosis of fatty liver at any time point, as captured by ICD-10 codes, or recorded in the problem list coded in the electronic health records. Other causes of chronic liver disease were excluded. Prospective assessment of randomly selected patients who presented to diabetes outpatient clinics and consented for a Fibroscan was then undertaken over a 5 month period. Steatosis was defined as CAP>250db/m² for M probe, CAP > 263db/m² for XL probe (1). MASLD was defined by the AASLD 2023 consensus criteria. Significant fibrosis was defined as LSM ≥ 8.0kPa (1). Clinical records were assessed for severity of diabetes, complications, and presentations related to MACE. FIB-4 score ≥ 1.3 and NAFLD-fibrosis score ≥ -1.455 were considered at risk for advanced fibrosis (1).

Results: Records of 16,055 inpatient and 1,513 outpatient diabetes patients were assessed. The prevalence of fatty liver was 2,715 (17%) and 325 (21%) respectively. Of 73 patients prospectively evaluated by Fiboscan, 65 had a valid scan (37 with T2D, 21 with T1D and 7 with secondary forms of diabetes), of which 74% had MASLD (95% of T2D and 43% of T1D). Of those with MASLD, 35% had significant fibrosis (51% T2D and 19% T1D). The presence of MASLD in diabetes was associated with older age (62 vs 54 years, p=0.04), higher BMI (33 vs 26 kg/m², p=0.001) and higher ALT (32 vs 27 U/L, p=0.02), but male sex (60% vs 33%) median duration of diabetes (17yrs vs 17 yrs), and HbA1c (8.5% vs 8.7%) were not significantly different. Recurrent unexplained hypoglycaemia was more common in diabetes with MASLD vs diabetes without MASLD (54% vs 24%, p=0.047), but there were no difference in MACE outcomes, microvascular and macovascular complications. FIB-4 scores had a sensitivity of 55% and specificity of 74% while NAFLD-fibrosis scores had a sensitivity of 82% and specificity of 36%.

Reference

1. Castera, L et al. Noninvasive Assessment of Liver Disease in Patients WithNonalcoholic Fatty Liver Disease. Gastroenterology. 2019 Apr; 156(5): 1264-1281.e4. https://doi.org/10.1053/j.gastro.2018.12.036.

346

Effects of the very low energy diet compared to a mediterranean diet on hepatic and metabolic outcomes in metabolic associated steatotic liver disease: A randomised controlled trial

Ann Farrell^1,2, Tonya Paris³, Evelyn Parr⁴, Elena George³, Jessica Howell^1,2,5, Catherine Croagh^1,2, Mark Page^1,2, Tom Sutherland^1,2, Penny McKelvie^1,2, Alexander Thompson^1,2 and Marno Ryan^1,2

¹St Vincent's Hosptial Melbourne, Melbourne, Australia; ²University of Melboourne, Melbourne, Australia; ³Deakin University, Geelong, Australia; ⁴Australian Catholic University, Melbourne, Australia; ⁵Burnet Institute, Melbourne, Australia

Background and Aim: Managing metabolic associated steatotic liver disease (MASLD) is challenging, and weight loss is the primary treatment. Guidelines suggest a Mediterranean diet (MD) may be optimal. Very low energy diets (VLED) and adjunctive appetite suppressing medications like semaglutide are used for medical obesity management. We hypothesised this medical weight loss approach could be used to treat MASLD and aimed to compare the VLED to an isocaloric MD on reducing hepatic steatosis by MRI liver fat fraction (MR-LFF).

Methods: A single-centre prospective RCT of adults with biopsy confirmed MASLD and BMI 27-35kg/m², randomised 1:1 to VLED or MD, stratified by gender and type 2 diabetes mellitus. Primary outcome was change in hepatic steatosis by MRI-LFF at 12 weeks. Secondary outcomes included changes in weight and metabolic parameters. After the 12-week diet, all participants were given dietary education regarding weight maintenance but able to eat to their own preferences. The VLED group were also prescribed low dose semaglutide (0.5mg weekly) from week 13 to assist with weight maintenance. Repeat MRI and liver biopsy were performed at week 24.

Results: 25 participants were randomised; 24 and 23 provided data to weeks 12 and 24 respectively. At 12 weeks the VLED was associated with a greater relative reduction in MR-LFF, -77%(IQR -88 - -51), vs -14%(IQR -30-0) in the MD(p<0.01). The VLED also resulted in greater total body weight loss -13% (IQR -16.9 - -9.1), vs -4% (IQR -4.4 - -0.2) in the MD (p<0.01). Both diets improved ALT and insulin resistance by homeostatic model assessment (HOMA-IR) and resulted in changes to body composition (Figure 1). At 24 weeks, the VLED/semaglutide group had no additional benefits in MR-LFF (-0.5%(IQR -1.8-3.7) p=0.75), or weight (-1.4kg(IQR -2.7-0.1) p=0.33) from week 12. The MD group had an increased MR-LFF [3.3%(IQR 1.7-6.5) p=0.03] but no weight change [0.8kg(IQR 0.4-3.2) p=0.07]. At 24 weeks, there was greater histological benefit via improved steatosis score ([-1.5(IQR -2 - -1) p<0.01] and hepatocellular ballooning (-1(IQR -1-0) p=0.02) in the VLED group. The MD also improved steatosis (-1(IQR -1-0) p=0.01) but less than the VLED (p=0.02). No change in fibrosis stage was seen in either group (VLED 0(IQR -1-0); p=0.18 vs MD 0(IQR 0-0); p=0.16).

356

The utility of the Gender Equity Model for Liver Allocation (GEMA) score for estimating the short term prognosis of patients with decompensated cirrhosis: Further evidence for the gender bias of the MELD score?

Brooke Colledge², Natalie Commins¹, Rohit Gupta¹ and James O'Beirne¹

¹Sunshine Coast University Hospital, Birtinya, Australia; ²University of New South Wales, Sydney, Australia

Background and Aims: The Gender Equity Model for Liver Allocation (GEMA) was developed to address inherent inequity in Model for End Stage Liver Disease (MELD) based scores in organ allocation. Lower muscle mass leads to lower serum creatinine concentrations in women compared to men, which does not reflect their true renal function resulting in systematically lower calculated MELD scores. The GEMA model replaces creatinine with a validated measure of renal function in cirrhosis (the Royal Free Hospital glomerular filtration rate -RFHGFR). GEMA has been validated in UK and Australian cohorts of patients awaiting liver transplantation and shows better discrimination than MELD based scores especially in females. As GEMA provides a better estimation of mortality risk in patients awaiting transplantation, we hypothesised that GEMA would also perform better in estimating short term prognosis than MELD in non-waitlisted patients admitted to hospital with decompensated cirrhosis.

Methods: Data was retrospectively analysed from a prospective database on 277 consecutive patients admitted to a tertiary centre with first presentation of decompensated cirrhosis within the study period (2016-2020). Patients who received a TIPS or liver transplant within 12 months of admission were excluded (n=14). Variables were collected to calculate MELD and GEMA. Survival was assessed at 90 days.

Results: The commonest causes of cirrhosis were alcohol (63%), MASLD (15%) and HCV (5%). The most frequent decompensation events were development of ascites (35%), upper GI bleeding (30%) and hepatic encephalopathy (11%). Median age was 60 (IQR 52-67). 65% were male. There was no significant difference in age between males (median 60, IQR 52-68) and females (median 59, IQR 51-66). 90 day survival was 68% in males and 78% in females (P=NS). The median MELD at admission was 16 (12-19). Median MELD in patients who died by day 90 was 18 (IQR 13-24) in males and 16 (IQR 13-23) in females P =NS. There was no significant difference in MELD scores between females who died by day 90 (MELD 15, IQR 11-18) compared to those that survived (MELD 16, IQR 13-23) P=0.12 although MELD was significantly higher in males that died by day 90 (18, IQR 13-24) than those that survived (15, IQR 12-18) P=0.03. Unlike MELD, GEMA was significantly higher in females that had died by day 90 (MELD 17, IQR 14-25) than those that survived (MELD 16, IQR 12-20) P=0.03. The median difference between GEMA and MELD was 0 in males (IQR -3-1.75) and 1 in females (IQR -1.5 – 3) P=0.0001. The AUROC curve for GEMA (0.6418) was higher than MELD (0.6) although there was overlap in the confidence intervals. In multivariable analysis, age (HR 1.032 CI 1.012-1.053 P=0.002) and GEMA (HR 1.141 CI 1.034-1.260 P=0.009) were significant predictors of 90 day mortality whereas MELD was not (HR 0.9541 CI 0.87-1.041 P=0.29).

Conclusion: In this single centre cohort of patients admitted with first decompensation of chronic liver disease, GEMA was superior at estimating short term prognosis compared to MELD and this was especially evident in females, further confirming the gender based limitations of MELD. Further studies using larger datasets are warranted to explore the prognostic value of GEMA in this patient group.

357

Hepatitis C RNA reflexive testing utilising a single blood sample collected in the Australian emergency department setting can be done

Julia Di Girolamo^1,2, David Prince^1,2,3, Robert Porritt⁴, Kiran Thapa⁴, Melissa Bagatella¹, Sicha Manandhar¹, Alex Prudence¹, Hong Foo⁴, Michael Maley⁴ and Miriam Tania Levy^1,2,3

¹Department of Gastroenterology and Liver, Liverpool Hospital, Liverpool, Australia; ²Ingham Institute for Applied Medical Research, Liverpool, Australia; ³The University of New South Wales, Sydney, Australia; ⁴NSW Health Pathology, Liverpool Hospital, Liverpool, Australia

Background and Aim: Case detection remains a challenge for hepatitis C virus (HCV) elimination. Recognised plateauing of testing and diagnosis rates suggest the need for implementation of universal screening programs, however HCV diagnostic testing methods may be a barrier. Australian guidelines recommend a sequent approach to hepatitis C diagnostic testing with an initial hepatitis C antibody (HCV Ab) serology assay, followed by a molecular confirmation of active infection using polymerase chain reaction (PCR) of hepatitis C RNA. The latter often requires patient recall for a new specimen collection. This multi-step process is complicated by instances of loss to follow up and introduces inefficiencies as many recalled patients may not have active infection. Laboratories may, at first blood collection, reserve a second blood tube in advance of an antibody test to reduce patient recall, however this is not a practical solution in the context of large-scale automated universal hepatitis screening programs.We have reported findings of a novel pilot Screening Emergency Admissions at Risk of Chronic Hepatitis (SEARCH). In this paper we describe the outcomes of a novel hepatitis C RNA reflexive testing process.

Methods: During SEARCH operation at a single tertiary hospital site in Sydney Australia, a computer algorithm automatically added HCVAb tests when an adult underwent routine biochemistry testing in ED. Initial positive HCV Ab serology results were identified and if sufficient volume available (minimum 650 μL) specimens were retrieved from the Cobas e801 biochemistry analyser, aliquoted for PCR testing of HCV quantitative nucleic acid on Cobas 4800 instrument. All patients were recalled for a subsequent HCV RNA to confirm the validity of the reflexive results.

Results: SEARCH tested 5206 patients and yielded 146 (2.8%) HCV Ab positive serology specimens eligible for reflexive HCV RNA testing. The proportion successfully tested by HCV RNA reflexive methodology was 55/146 (38%) of which, 7 (13%) were positive, 47 (85%) were negative and 1 invalid. Testing could not be performed on 91 (62%) due to insufficient sample volume. Of the 54 with valid results, 33 (61%) to date, have been recalled for a subsequent HCV RNA test to confirm the validity of the reflexive results. Six of the seven RNA positives were able to be confirmed (one patient died). Of the 47 RNA negative, 27 (57%) were confirmed and 16 (8.5%) are currently in follow up. Two were lost to follow up and a 2 declining further testing. No false positive or false negative results were identified using the reflexive HCV RNA single tube methodology.

359

Screening for viral hepatitis in the emergency department – the methodology to automate a feasible, acceptable and effective solution

Julia Di Girolamo^1,2,3, David Prince^1,2,3, Basheer Alshiwanna¹, David Thomas⁴, Shahida Bakridi⁴, Sophie Gryllis⁴, Maria Tiglao⁴, Rebecca Haack⁴, Kristian Peralta⁴, Melissa Bagatella¹, Irena Petrovski⁵, Julie Doan⁶, Richard Cracknell⁷, Jeremy Lawrence⁸, Michael Maley⁴, Hong Foo⁴, Nathan Jones¹⁰, Gregory Dore⁹ and Miriam Tania Levy^1,2,3

¹Department of Gastroenterology and Liver, Liverpool Hospital, Liverpool, NSW Australia, Liverpool, Australia; ²Ingham Institute for Applied Medical Research, Liverpool, Australia; ³The University of New South Wales, Sydney, Australia; ⁴NSW Health Pathology, Sydney, Australia; ⁵Department of Gastroenterology and Liver, Campbelltown Hospital, Campbelltown, Australia; ⁶Clinical Reporting and Analytics, Liverpool Hospital, Liverpool, Australia; ⁷Department of Emergency Medicine, Campbelltown Hospital, Campbelltown, Australia; ⁸Department of Emergency Medicine, Fairfield Hospital, Fairfield, Australia; ⁹The Kirby Institute, UNSW, Sydney, Australia; ¹⁰Liverpool Hospital, Liverpool, Australia

Background and Aims: Australian guidelines recommend risk factor screening for viral hepatitis in priority populations. Barriers to testing exist in culturally and linguistically diverse (CALD) and Indigenous populations particularly, who may acquire hepatitis via non-injecting use routes. A universal testing strategy may serve hard to reach populations, but implementation remains an issue. We reported Screening of Emergency Admissions at Risk of Chronic Hepatitis (SEARCH) pilot clinical service in Emergency Department (ED) screening of priority populations, efficacy, cost utility, and acceptability. This report describes the methodology required for automation and broad implementation.

Methods: A novel pilot clinical service (SEARCH 3X) was developed to automatically test adult ED patient blood specimens for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCVAb). A computer algorithm was developed such that at laboratory specimen reception in appropriate specimens, hepatitis serology would be automatically added, directing the specimen through the biochemistry analyser for testing. Positives were confirmed by routine supplementary tests. A re-test order within seven days was automatically denied. The feasibility of reflexive HCV RNA testing on positive HCVAb specimens was examined. Test cancellation mechanism due to patient or clinician request, was developed. Design included the automatic reporting of positive results to the clinical team to precipitate linkage to care. Clinician and patient education resources were developed to promote awareness of viral hepatitis and the testing service, in the form of videos, posters, pamphlets and website including translation into languages for local CALD communities.

Results: Six Australian EDs were identified in metropolitan or rural locations based on feasibility and unmet need. Executive and clinical stakeholders were consulted, and a governing steering committee formed. An initial pilot of 5000 patients per site was set. The automated methodology was successfully implemented in the first two sites with minimal impact on ED services. Ninety-nine percent (n=10,204) of eligible patients were successfully tested. The combined HBsAg and HCVAb seroprevalence was 2.5%. Eighty six percent of positive patients were successfully linked to care. No patient or staff complaints were received, nor did any patient decline testing. The proportion of patients tested more than once was 10.5%, of which 80%, were tested twice,15% tested thrice and remainder 5% tested four to six times.

380

Safety of apixaban at time of liver transplant: A retrospective case-control study

Katrina Tan, Elizabeth Low, Jacqueline Balassone, Adam Testro, Avik Majumdar and Marie Sinclair

Austin Health Liver Transplant Unit, Heidelberg, Australia

Background and Aim: Novel oral anticoagulants such as apixaban are commonly prescribed for management of portal venous thrombosis (PVT) in patients awaiting orthotopic liver transplantation (OLTx).(1) Continuation of anticoagulation until OLTx is paramount to maintaining portal vein patency. There is a paucity of data surrounding safety of liver transplantation in patients therapeutically anticoagulated with apixaban. This study aimed to assess the safety of OLTx in patients anticoagulated with apixaban. The primary outcome was the number of intra-operative blood products required (packed red blood cells (PRBC)) and cycles of intra-operative cell salvage (ICS)) and return to theatre for bleeding complications in the first 72-hours post-transplant. The secondary outcomes were graft failure and patient survival at 12 months.

Methods: A case-controlled, retrospective analysis of adult patients who received OLTx between 1^st January 2018 and 31^st December 2023 was conducted at an Australian liver transplant centre. Cases were identified from the centre’s electronic liver transplant registry. Patient’s electronic medical records were reviewed to obtain demographics, apixaban prescription, operation reports and blood product administration. Controls were randomly selected from the registry’s remaining patients who were transplanted within the same time interval and matched in a 2:1 ratio to the cases based on sex, age, transplant indication and MELD score (p>0.05 for age, MELD score). Univariate analysis with Mann-Whitney U, Chi-squared and Fisher’s exact tests were performed to assess for differences between blood products required and post-operative outcomes.

Results: Over the 5-year study period, 26 patients were identified to be anticoagulated with apixaban at the time of OLTx. The median age was 64 years and 62% were male. 52 controls (62% male) were included, with a median age of 62 years. Cases were considered as therapeutically anticoagulated if apixaban was continued to within 24h of OLTx. Indications for apixaban included thromboses within the portal vein (n=22, 88%), superior mesenteric vein (n=2), splenic vein (n=3) or IVC (n=1). There was no significant difference found between the median intra-operative PRBC requirements between patients in the apixaban group (4 units, IQR 2-8) compared to the control group (3.5 units, IQR 2-8) (Table 1). Similarly, no significant differences between cases and controls were found for median number of ICS cycles (apixaban group = 5 cycles (IQR 2-10) vs. control group = 3.5 cycles (IQR 2-20). There were no cases in the apixaban group that returned to theatre for bleeding complications. 7 cases (13%) in the control group returned to theatre within 72h of OLTx for post-operative bleeding. The odds of requiring return to theatre were not statistically different despite apixaban use preceding OLTx. No significant differences in incidence of graft failure or 12-month survival were found.

Table 1:

Conclusion: While apixaban has commonly been used for management of porto-mesenteric thromboses prior to liver transplantation, concerns regarding safety of OLTx in these recipients have been raised. Experience from a tertiary Australian liver transplant center demonstrates that patients anticoagulated with apixaban at time of liver transplant had no significant peri-operative bleeding complications, nor significantly increased blood product requirements during OLTx. Graft and patient survival were not statistically different between patients treated with apixaban and those not.

Reference

1. Franchis, R, Bosch, J, Garcia-Tsao, G, etl al; Baveno VII Faculty. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022 Apr; 76(4): 959-974.

381

MELD 3.0 does not improve liver transplant waiting list prioritisation over MELD or MELD-Na in Australia and New Zealand

John Chetwood^1,2,3,4, Lauren Tang⁵, Mandy Byrne⁵, Michael Fink^5,6, Robert Jones^5,6, Geoffrey McCaughan^1,3, Simone Strasser^1,3, Michael Crawford^1,3, Carlo Pulitano^1,3, Peter Hodgkinson⁷, Katherine Stuart⁷, Caroline Tallis⁷, John Chen⁸, Alan Wigg^9,10, Bryon Jaques^9,10, Gary P Jeffrey^9,10, Leon A Adams^9,10, Ed Gane^11,12, Louise Barbier¹¹, John McCall¹³, Danny Con⁵ and Avik Majumdar⁵

¹Australian National Liver Transplant Unit, Royal Prince Alfred Hospital, Sydney, Australia; ²Concord Repatriation General Hospital, Sydney, Australia; ³University of Sydney, Sydney, Australia; ⁴St Vincents Hospital Melbourne, Melbourne, Australia; ⁵Victorian Liver Transplant Unit, Austin Health, Melbourne, Australia; ⁶Department of Surgery, Austin Health, Melbourne, Australia; ⁷Queensland Liver Transplant Service, Princess Alexandra Hospital and Queensland Children’s Hospital, Brisbane, Australia; ⁸South Australian Liver Transplant Unit, Flinders Medical Centre, Adelaide, Australia; ⁹WA Liver Transplant Service, Sir Charles Gairdner Hospital, Perth, Australia; ¹⁰Medical School, University of Western Australia, Perth, Australia; ¹¹New Zealand Liver Transplant Service, Auckland City Hospital and Starship Children’s Hospital, Auckland, New Zealand; ¹²Department of Medicine, University of Auckland, Auckland, New Zealand; ¹³Department of Surgical Sciences, University of Otago, Auckland, New Zealand

Background and Aim: Controversy exists regarding the best predictive model of liver transplant (LT) waiting list (WL) mortality. MELD 3.0 has been proposed to provide better prognostication, particularly in females.

Methods: All consecutive patients with cirrhosis waitlisted for LT 2010-2020 were examined from the Australian and New Zealand Liver and Intestinal Transplant Registry, where organ allocation is guided by MELD. The primary outcome was 90-day WL delisting due to death or clinical deterioration within 90-days. MELD 3.0, MELD, & MELD-Na at time of WL registration were compared. Model discrimination was assessed with Harrell’s C-index & area under the receiver operating characteristic curves (AUROC). Model calibration was examined with Grønnesby & Borgan’s modification of the Hosmer-Lemeshow formula. Re-classification was calculated where MELD 3.0 and MELD-Na were used instead of MELD with a resultant score change ≥2 points.

Results: The study population comprised 2,868 patients with a median age of 56.7 (IQR: 50.5-61.6) years and male predominance (74.1%). The Harrell’s C index for the primary outcome indicated good discriminatory performance for all scores (0.77, 0.78 & 0.77 for MELD, MELD-Na and MELD 3.0 respectively), yet there was no difference in predictive capacity between scores (P>0.05 versus MELD), including in the subgroups of females and those without hepatocellular carcinoma (HCC). Similarly there was no difference between scores for 30-days outcomes including in subgroup analysis. Both MELD-Na & MELD 3.0 outperformed MELD for 1-year outcomes overall and without HCC (P<0.05), though not in the female subgroup. However, there was no difference between MELD-Na vs MELD 3.0 for 1-year outcomes overall nor in subgroup analysis (all P>0.05). Similarly, via AUROC analysis all scores performed well in predicting 90-day outcomes (AUROC: ≥0.85), yet there was no difference between scores (all P>0.05 versus MELD), including in females and without HCC (all P>0.05 versus MELD). MELD-Na was the only well-calibrated score (Grønnesby & Borgan c²=16.81, P=0.05). MELD 3.0 and MELD-Na versus MELD re-classified 77.9% & 45.9% of the cohort respectively. MELD 3.0 instead of MELD-Na reclassified 67.5%. However, the prevalence of the primary outcome was higher when patients were prioritised by MELD.

388

Cause-specific mortality among Australians with cirrhosis differs by cirrhosis aetiology and decompensation status

Vikas Bhasker^1,2, Paul J Clark¹, Gunter Hartel², Richard Skoien³, Elizabeth Powell^1,2 and Patricia Valery²

¹Princess Alexandra Hospital, Woolloongabba, Australia; ²QMIR Berghofer Medical Research Institute, Herston, Australia; ³Royal Brisbane and Women's Hospital (RBWH), Herston, Australia

Background and Aim: Liver disease in Australia is among the top 10 leading causes of years of life lost, with a 10% increase in disease burden during 2003-2022. Over the last decade, there have been advances in treatment and a change in the prevalence of aetiological factors and comorbidities of liver disease. However, Australian data are limited about the principal causes of death among people living with cirrhosis. Using QLD-wide data we determined cause-specific mortality in people with cirrhosis according to liver disease aetiology and severity.

Methods: A retrospective analysis of adults hospitalized for cirrhosis during 2007-22 was performed using state-wide hospital admissions and mortality data. ICD-10 codes identified admissions with cirrhosis, aetiology, and underlying (UCOD) or contributing (CCOD) cause of death based on validated algorithms. Patients were considered to have cirrhosis decompensation (CD) if they had at least one admission with variceal bleeding, ascites or hepatic encephalopathy.

Results: 22,525 individual patients had at least one admission with cirrhosis and/or died with cirrhosis as UCOD or CCOD, with a median follow-up of 6.9 years (interquartile range 3.5-11.1). At index admission mean age was 61.2 years (SD=13.0) with a male predominance (66.1%). The most common cirrhosis aetiologies were alcohol (n=9,550, 42.4%), MASLD/Cryptogenic (n=5,108, 22.5%) and hepatitis C virus (HCV) (n=4,780, 21.2%). During follow-up, 12,387 (55%) patients died, with overall mortality 57.9%, 52.1% and 51.6% among alcohol, MASLD and HCV subgroups, respectively (p<0.001). The UCOD was liver disease in 50.3% and varied significantly by cirrhosis aetiology and CD status (p<0.001; Figure). Following inclusion of CCODs, liver-related deaths were reported in 79.1%, 54.9% and 86.9% in the alcohol, MASLD and HCV subgroups, respectively. Moreover, in patients with MASLD, other key UCOD/CCODs included major adverse cardiovascular events (42.4%), extrahepatic cancer (25.2%), respiratory disease (23.6%), and diabetes (23.8%).

396

Outcomes of hepatocellular carcinoma in patients treated with radiofrequency ablation

Sarah Ng and Sam Galhenage

Fiona Stanley Hospital, Perth, Australia

Background and Aim: Radiofrequency ablation (RFA) is one of the most popular alternatives to curative resection or transplant in early-stage hepatocellular carcinoma (HCC). Studies have shown that RFA has no significant difference in long term survival compared to transplant or resection¹. Guidelines suggest use of RFA In early HCC, Child-Pugh A or B status of ≤3cm in diameter and ≤3 tumours in total. Main advantages of RFA being its ability for excellent tumour control with minimally invasive nature and acceptable morbidity. Main disadvantages being a limited ablation zone of maximum 4-5cm in diameter, heat sink effect and needle track seeding. Literature suggests a 5-year survival rate of 40-68% with factors negatively affecting survival including: high alpha-fetoprotein (AFP), Child-Pugh B status or presence of portosystemic collateral vessels. Surgical resection is regarded as first line treatment for patients with well-preserved liver function but nonetheless, almost 70% develop rumour recurrence within 5 years after surgery. The aim of this project was to look at overall survival and progression-free survival in HCC patients treated with RFA in our local cohort.

Methods: This was a retrospective study identifying 50 patients from a tertiary centre in Perth, Western Australia who underwent RFA or microwave ablation (MWA) from January 2018- January 2023. Hospital electronic records were reviewed, and data points collected included: age, gender, cirrhosis status, Child-Pugh status, aeitiology, tumour size, tumour location, tumour recurrence vs new tumour location and complications.

Results: Of the 50 patients, 38 were male and 12 were female with a mean age of 67. 48 patients were cirrhotic (45 CPA and 3 CPB) and 2 were non-cirrhotic. Most common aetiology of liver disease being alcohol-misuse followed by hepatitis C infection and metabolic- associated liver disease. Mean size of HCC under active ultrasound surveillance was 20.8mm and mean size of HCC not under active ultrasound surveillance was 19.6mm, with no clinical significance between the 2 groups. Tumour recurrence occurs in 48% of patients at an average of 20.2months with 58% being right lobe tumours and 42% being left lobe tumours. Patients with a positive AFP (>10) were more likely to develop a new HCC compared to negative AFP at initial presentation. Fig.1 shows the overall survival with 1-year survival at 97.8%, 3-year survival at 95% and 5-year survival at 58%. Eleven percent, 31% and 78% developed a new HCC at 1-year, 3-years and 5-years respectively.

Conclusion: Overall survival and progression-free survival in RFA are compatible to liver resection with being a much less invasive treatment option Positive AFP had a positive correlation with tumour recurrence, and careful patient selection is required.

399

The views and practices of gastroenterologists regarding integrated multidisciplinary care for the management of co-occurring alcohol-related liver disease and alcohol use disorder

Angus Ferguson^1,2, Paul Haber^3,4, Vicky Phan² and Victoria Manning²

¹Western Health, St Albans, Australia; ²Turning Point, Monash University, Richmond, Australia; ³Royal Prince Alfred, Camperdown, Australia; ⁴University of Sydney, Sydney, Australia

Background and Aim: To explore Gastroenterologists current practices and confidence in identifying and managing Alcohol Use Disorder (AUD) within the Victorian healthcare system and to assess the extent of local barriers and facilitators to integrated multidisciplinary services with Addiction Medicine & Alcohol and Other Drug services for the ongoing management of patients with AUD and Alcohol-related Liver Disease.

Methods: An anonymous cross-sectional survey of Gastroenterologists and Advanced Trainees in Victoria, Australia specifically assessing confidence and skill in screening and treating AUD; ability and willingness to manage AUD including prescribing alcohol pharmacotherapies; potential barriers and facilitators for integration of addiction services in Gastroenterology.

Results: 30 Gastroenterologists and trainees completed our survey. 23 doctors (76.7%) reported no previous training in Addiction Medicine, and only 10 (33.3%) felt comfortable both identifying and managing AUD. 21 (70%) did not regularly prescribe pharmacotherapy treatments predominantly due to insufficient experience (n=13, 43.3%). Lack of training in Addiction Medicine was the most common barrier to AUD management (n=24, 80%), and formulation of institutional guidelines and development of integrated multidisciplinary clinics were the most popular ways to facilitate integration (n=24, 80% and n=22, 73.3% respectively).

Conclusion: Victorian (and by extension, Australian) Gastroenterologists are similar to their colleagues internationally in recognising the need for integration of Addiction Medicine services into their clinical roles. Training in AUD is the biggest barrier to providing care, however their preference is for organisational guidelines and multidisciplinary clinics rather than formalised training programs. Establishing the structure and logistics of such integration in Australia requires further research prior to implementation.

407

Improved mortality associated with a specialist liver home-based care program for patients with cirrhosis following hospitalisation

Leya Nedumannil¹, Catherine Yu¹, Kristen Peake¹, Vanessa Lowen¹, Kendall Fitzpatrick¹, Mustafa Mohamedrashed¹, Diana Lewis¹ and Siddharth Sood^1,2

¹The Northern Hospital, Epping, Australia; ²The University of Melbourne, Parkville, Australia

Background and Aim: Liver At Home (L@H) is a liver-focused 3-month home-based care program involving regular specialist liver nurse-led home visits and/or telehealth reviews. L@H aimed to facilitate continued medical managements of patients with chronic liver disease in the community following discharge from hospital. We examined readmission and mortality outcomes in patients with cirrhosis enrolled during the first year of L@H.

Methods: Patients with cirrhosis enrolled to L@H between 01/03/2023-01/03/2024 were compared to patients with cirrhosis who were referred but not enrolled. Only index enrolments were included. Reasons for non-enrolment included ineligibility based on home safety screening, residence outside the hospital catchment, and patient preference. Admission back to hospital within 0-7 days was considered a failed discharge, whilst 8 days-3 months was defined as readmission. Differences between the enrolled and non-enrolled groups were evaluated using intention-to-treat analysis, and Cox proportional hazards regression as used to compare survival and readmission outcomes.

Results: 47 index L@H patients were compared to 24 non-L@H patients. There were no significant differences between L@H and non-L@H patients with respect to median age (60 vs 58.5 years, p=0.37), gender (33% vs 46% female, p=0.25), and non-English speaking proportion (28% vs 17%, p=0.31), respectively. Cirrhosis severity was also similar with median MELD-Na score 19 (IQR 13-23) in L@H vs 18 (IQR 13-20.5) in non-L@H patients (p=0.33). The proportion of failed discharges was similar at 4.2% in both groups (p=0.99). 3-month follow-up demonstrated a trend towards reduced liver-related hospital readmission [25% (n=12) vs 33% (n=8), hazard ratio (HR) 0.70 (0.30-1.60)], and all-cause mortality [6.3% (n=3) vs 25% (n=6), HR 0.30 (0.01-1.10)] in L@H patients. During extended follow-up [median 28 weeks (IQR 17-47), total 2175 patient weeks], a statistically significant sustained mortality benefit associated with the L@H program was observed [15% (n=7) vs 42% (n=10), HR 0.30 (0.1-0.8), p=0.0086] (Figure 1).

Conclusion: This study demonstrates a sustained reduction in all-cause mortality associated with enrolment to L@H in recently hospitalised patients with cirrhosis, relative to a comparator non-enrolled group, despite similar patient demographics and cirrhosis severity. Furthermore, L@H patients appeared to exhibit a trend towards reduced liver-related readmission to hospital. Our findings suggest that not only does L@H have potential benefits in reducing liver-related hospital readmission and all-cause mortality in patients with cirrhosis following hospital admission, but that these mortality benefits may extend well beyond the program’s completion. Further research will be undertaken to identify factors associated with improved survival in L@H patients in comparison to a propensity matched cohort.

411

Scratching beneath the surface of primary biliary cholangitis: Time to refocus on patient symptoms and clinical targets

Shamya Putta, Rohit Gupta, Lucy Vaux, Andrew Sloss, Tehara Wickremeratne and James O'Beirne

Sunshine Coast University Hospital, Birtinya, Australia

Introduction: Primary Biliary Cholangitis (PBC) is an autoimmune, chronic liver disease, characterised by damage to small, intrahepatic ducts. PBC can often lead to debilitating symptoms, including pruritis and fatigue. Alkaline phosphatase (ALP) is used as a marker to assess response to therapy and disease activity; guidelines recommend a target below levels of 1.67 times the upper limit of normal (ULN); however, recent data has suggested ALP taget be towards normalisation. The study aims to assess patients' quality of life and disease burden with PBC and assess if clinical targets are achieved.

Methods: A retrospective cohort study assessing patients with PBC seen in the liver clinic was completed. Inclusion criteria consisted of a clinical diagnosis of PBC based on histological or autoimmune markers. The most recent ALP and bilirubin levels were included, and GLOBE scores were calculated based on these results. Additionally, Model for end-stage liver disease (MELD) and Child-Pugh scores were calculated. Patient symptoms were assessed using the itch score, short-form fatigue score, and PBC-40 with various domains separated.

Results: 37 patients were included in this retrospective study, 80% of which were female, and the overall mean age was 68 years old. The mean ALP level was 143 and 85.7% of patients had met the target of ALP being below 1.67 times the upper limit of normal (110 U/L). In comparison, when targeting an ALP that was equal to or less than upper limit of normal ALP, 40% of patients had met this target. On review of medications, 14.3% of patients were on two agents for PBC, UDCA with either obeticholic acid or fenofibrate, 80% of patients were on a single agent and 5.7% of patients were not on any disease modifiying PBC medication. The highest scoring domains on the PBC-40 was fatigue with a mean score of 3.01 (SD = 0.857) as highlighted in Figure 1.

414

Targeted liver biopsies - are they hitting the mark? An audit

Eda Gungormez¹, Leya Nedumannil¹, Natasha Walker¹, Siddharth Sood^1,2 and Diana Lewis¹

¹Northern Health, Epping, Australia; ²University of Melbourne, Parkville, Australia

Background and Aim: Targeted liver biopsies are an important diagnostic and prognostic tool in the investigation of radiologically ambiguous lesions. While defined criteria for non-targeted liver biopsies have been established, the quality assessment of targeted biopsies remains unclear. This study aimed to investigate factors impacting the quality of, and complications related to targeted liver biopsies.

Methods: A retrospective audit was conducted on targeted liver biopsies performed at a single health service between 2021-2023. Key variables included the specialist conducting the biopsy (interventional radiologist (IR), surgeon, endoscopist), method (percutaneous, surgical, endoscopic), indication, biopsy size (length), biopsy-derived diagnosis, and biopsy-related complications. Biopsies that were non-diagnostic and those with procedure-related complications were further analysed.

Results: Of 169 liver biopsies performed, 101 (59.76%) were targeted [median age 67 years (± 17), 54.46% female]. International normalised ratio (INR) and platelet values were not available pre-procedurally in 15.84% and 13.86% of biopsies, respectively. Most biopsies were performed percutaneously by IR (97.03%, n=98), followed by 1.98% (n=2) endoscopically and 0.99% (n=1) surgically. Three (2.97%) targeted biopsies had periprocedural complications, all related to intraprocedural bleeding, and were performed by IR (median needle size 18G, equivalent to uncomplicated biopsies). Of those with complications, only one case had pre-procedural INR and two had platelet levels tested, and all within normal limits. Compared to uncomplicated cases, patients with complications had a median age of 62 years (± 24) vs 68.5 (± 15.5), and median Eastern Cooperative Oncology Group (ECOG) score of two vs one. Only 6.93% (n=7) of the biopsies were non-diagnostic, all of which were performed by IR with 85.71% using an 18G needle. There was a greater median number of samples per biopsy performed in the non-diagnostic group [4 ± 2 vs 3 ± 2, p=0.029]. The median length of samples was smaller in the non-diagnostic group compared with diagnostic samples, though not statistically significant [10mm ± 6.5 vs 12mm ± 9, p=0.17].

Conclusion: We identified higher ECOG score as a predictor of periprocedural complications in targeted liver biopsies. Diagnostic samples had a greater median length though this was not significant in our cohort. The higher number of samples in non-diagnostic biopsies may relate to smaller initial samples taken or inability to obtain larger sample sizes due to difficult-to-access lesions. Our research highlights the need for a larger-scale audit to predict the risk of periprocedural complications and define criteria for the quality of targeted liver biopsies.

417

An assessment of treatment preferences and clinical outcomes for ascites in patients with liver cirrhosis: A retrospective cohort study

Tsz Hong Yiu¹, Aisha Khalid^1,2, Hans Mautong^2,3, Jennifer Andraos¹, Emily Matejin¹, Kerrie Curin¹, Nicola McGuinn¹ and Zina Valaydon^1,4

¹Western Health, Melbourne, Australia; ²Department of PGME (Post grade medical education), Harvard Medical School, Boston, United States; ³Department of Medicine, John H. Stroger Jr. Hospital of Cook County, Chicago, United States; ⁴Department of Medicine, University of Melbourne, Melbourne, Australia

Background and Aim: Recurrent ascites is a common complication of portal hypertension in liver cirrhosis patients. First-line management includes a salt-restricted diet and diuretics, followed by large volume paracentesis (LVP), albumin infusion, trans-jugular intrahepatic portosystemic shunt (TIPS) for refractory cases. Evidence supports a mortality benefit from albumin infusion and TIPS, whereas LVP is generally regarded as palliative. This study aims to assess treatment preferences of ascites and clinical outcomes at Western Health (WH), a tertiary health service in Melbourne, serving a population of 1.2 million with a high prevalence of alcohol-related liver disease.

Methods: We retrospectively collected data from the electronic medical records of all cirrhotic patients admitted to WH in 2021 with ascites. We documented the underlying liver disease and management options for ascites. Univariate and logistic regression analyses were performed to assess predictors of recurrent ascites and liver-related mortality over a 2-year follow-up period.

Results: Our study included 64 cirrhotic patients with symptomatic ascites, with a mean age of 60 years (SD 14.3), and 59.4% (n=38) male. The primary aetiologies were alcoholic liver disease (68.8%, n=44), metabolic liver disease (17.2%, n=11), hepatitis C (6.3%, n=4), and hepatitis B (4.7%, n=3). Disease severity was categorized as 17.8% (n=11) with Child-Pugh (CP) A cirrhosis, 53.1% (n=34) with CP-B, and 28.1% (n=18) with CP-C. Diuretics were prescribed for 87.5% (n=56) of the patients, and a high-protein, low-salt diet was prescribed by a dietitian for 56% (n=36) of the patients. While neither measure alone has been established to reduce recurrence, logistic regression analysis suggested the combination of both reduces the recurrence of ascites (OR 0.45, 95% CI 0.22 – 0.93, p=0.03). Of the 27 patients with recurrent ascites, 70% (n=19) received regular LVP. Their 2-year mortality rate was significantly lower than those who did not receive regular LVP (OR 0.07, 95% CI 0.007–0.66, p = 0.02). Logistic regression, accounting for age and CP status, confirmed a sustained mortality benefit with regular LVP (OR 0.07, 95% CI 0.005–0.87, p = 0.04). 2 patients received fortnightly albumin infusions, both of whom survived at 2 years. Only 1 patient received TIPS and died of non-liver related disease (strangulated hernia) within 2 years.

Conclusion: Our study suggests that combining diuretics with a high protein low-salt diet reduces the rate of recurrent ascites. Additionally, regular therapeutic LVP shows promise in reducing mortality. Albumin infusion and TIPS are underutilized and should be considered for managing recurrent ascites.

422

Medical therapy for drug-induced liver injury secondary to amoxicillin/clavulanic acid and atorvastatin: an observational analysis of the Australian Drug-Induced Liver Injury Network registry

Steven Trinh and Amanda Nicoll

Eastern Health, Box Hill, Australia

Background and Aim: Drug-induced liver injury (DILI) is an important cause of acute liver injury with amoxicillin/clavulanic acid (AMC) and atorvastatin among the common causative agents. There is limited data with regards to the benefits of medical therapy for DILI, and the only recommended treatment is withdrawal of the offending agent and supportive care. We report observational data from the Australian DILI Network on ursodeoxycholic acid (UDCA) and/or corticosteroids for patients with DILI from AMC or atorvastatin.

Methods: Patients with suspected DILI were prospectively enrolled as part of the Australian DILI registry across 14 healthcare centres in Australia from 2016. Patients with DILI due to AMC or atorvastatin were identified and analysed.

Results: Twenty-eight patients had DILI associated with AMC. Only eight of these patients had documented time to resolution and peak liver function tests (see Table 1). Older patients with jaundice secondary to AMC DILI were more likely to receive UDCA, and had a longer time to resolution. Twenty-five patients had DILI associated with atorvastatin. Fourteen of these patients had documented time to resolution and peak liver function tests (see Table 1). This data shows that the patients with more severe liver injury secondary to atorvastatin, as determined by ALT and bilirubin, received medical therapy.

423

Using a novel, point-of-care antibody test to improve screening rates for hepatitis C: results from a pilot trial in Western Sydney Local Health District

Jeenat Paulose¹, Nishita Jagarlamudi¹, Jeffrey Dabbhadatta², Susan Markovic¹, Dmitrii Shek^1,3, Ian Wong¹ and Golo Ahlenstiel^1,3

¹Blacktown Hospital, Blacktown, Australia; ²HIV and Related Programs (HARP), Western Sydney, Australia; ³Western Sydney University, Western Sydney, Australia

Background and Aim: Hepatitis C virus (HCV) infection is a blood-borne virus that causes liver cirrhosis and can lead to hepatocellular carcinoma and liver failure. New South Wales (NSW) Health has a hepatitis C strategy to aim for elimination of Hepatitis C by 2028 which requires increase in treatment initiation. This pilot aims to increase testing for patients and improve screening rates of Hepatitis C testing using a novel point-of-care antibody test; HCV Bioline by Abbott (sensitivity 100% (95% CI: 97.76 – 100) and specificity 100% (98.85 – 100), invalid rate 0%). The novel testing method also aims to reduce stigma and discrimination as barriers to testing and increase visibility of the disease and thus improve user acceptance.

Methods: The pilot study was completed as a prospective, cohort study. Participants were offered point-of-care testing as they accessed services at a community oral health clinic. Participants were required to complete a pre-test questionnaire and consent for the study. They were offered a novel point-of-care, finger-prick rapid test: Abbott’s Bioline HCV kit to diagnose HCV. They received results within 5 to 20 minutes of taking the test. Positive patients were provided a pathology referral on the day and directed to complete further blood tests. Any patients subsequently identified to be positive for HCV RNA received an appointment in the liver clinic for further investigation and management.

Conclusion: This pilot uses a novel, point-of-care, finger-prick rapid antigen test to diagnose current and previously treated HCV. The results from testing show excellent user acceptance with new linkage to care and good engagement with services. There is likely secondary benefit by improving health literacy through raising awareness of HCV infection. The ongoing study plans to capture patients attending outpatient services across the local health district and positively impact the micro-elimination strategy.

428

Reduction of unnecessary CT head use in cirrhotic patients presenting with hepatic encephalopathy

Vivienne Nguyen

Sir Charles Gairdner Hospital, Perth, Australia

Background and Aim: Hepatic encephalopathy (HE) is a neuropsychiatric complication often associated with cirrhosis, manifesting as a wide spectrum of changes in mental state. Currently, there is no pathognomonic imaging method or findings that exists to unequivocally diagnose HE. Low diagnostic yield of CT head (CTH) use in cirrhotic patients in the absence of focal neurological deficits (FND) have been demonstrated. Despite this, CTHs are still frequently used in evaluating patients with cirrhosis presenting with altered mental status (AMS), contributing to increased radiation exposure, prolonged duration in the Emergency Department (ED) and higher healthcare costs. This audit aimed to assess the trend of unnecessary CTH use in patients who presented to the ED with HE.

Methods: 155 consecutive encounters in the ED at a tertiary centre in Western Australia were identified retrospectively from 1 January 2022 to 31 December 2023 using electronic health record query ‘HEPATIC. Encounters were screened to include those with a history of cirrhosis presenting with AMS or suspected HE. Demographic, clinical and biochemical data were extracted. Descriptive analyses were performed. CTH use was considered necessary in the presence of high-risk features including history of trauma/fall, FND or age ≥ 65 years, based on local guidelines utilising the Canadian CT Head Injury Rule.

Results: 64 encounters were identified and included, with a male predominance (75%). Mean age was 62 years. 56 (88%) encounters had a documented history of prior HE. 44 encounters (69%) had alcohol has the aetiology of cirrhosis. CTH was requested for 41 (64%) of encounters. One abnormal CTH result was detected (2.4%) in the context of a falls history. 15 out of 41 cases (37%) had no high-risk indication for CTH including trauma/fall, FND, and were <65 years. All 15 cases had no acute abnormality on CTH. Of the 15 encounters, 14 (93%) had a prior history of HE and were known to a Hepatology/Gastroenterology department.

Conclusion: Results demonstrate a low prevalence (2.4%) of CTH abnormality in cirrhotic patients presenting with HE and a low yield of routine CTH in the absence of trauma or FND. Unnecessary CTH use was found to be ordered in over one third (37%) of presentations over a two year time frame. Findings support the suggestion that in the absence of high-risk factors such as falls/trauma, and in the absence of concerning examination features such as FND, CTH use should be avoided when cirrhotic patients present with suspected HE.

440

Outpatient paracentesis for patients with ascites in liver cirrhosis: a systematic review

Edward Meehan¹, Wendell Zhang¹, Nicholas Mulkearns², Cindy Truong¹, Liam Brennan-Xie², Olivia Otto², Ji Park¹, NJ Arachchi¹ and Zina Valaydon¹

¹Western Health, Footscray, Australia; ²University of Melbourne, Melbourne, Australia

Background and Aim: Tense ascites is a common cause of hospitalisations in patients with liver cirrhosis. Many hospitals operate outpatient paracentesis services to prevent re-admissions, but their characteristics, outcomes, and cost effectiveness have been poorly studied. We aimed to assess the clinical and cost effectiveness of outpatient paracentesis services and to describe outcomes in enrolled patients and current models of care.

Methods: We searched the Embase, OVID Medline, CENTRAL, and Web of Science databases in December 2023. We included primary research studies of all designs which described outpatient paracentesis services catering to patients with refractory ascites due to cirrhosis. We synthesised results using random effects meta-analysis and vote counting.

Results: We screened 8013 studies and included 65. Paracenteses were performed by physicians in 16 studies, nurses in 14, radiologists in 3, paramedics in 1, physician associates in 1, and unspecified providers in 30 studies. Ten studies (9 retrospective, 1 prospective) assessed the impact of outpatient paracentesis services on unplanned hospitalisations or length of stay, and all ten reported improvements in these outcomes. Five were before-after studies, one analysed a nationwide database, and four contained no comparison group. These four relied on the assumption that all outpatient paracenteses had averted a hospitalisation. This likely overestimates averted hospitalisations, given that another study reported that paracenteses per person increased after an outpatient service was introduced, suggesting some outpatient paracenteses occur sooner than hospitalisation would. All six studies measuring cost (4 retrospective, 2 prospective) found that outpatient paracentesis reduced costs, but only three made a before-after comparison. The other three again assumed that all outpatient paracenteses averted an admission. No studies assessed mortality or survival benefits of outpatient paracentesis services compared to their absence, but one randomised trial compared patients allocated to serial outpatient paracentesis versus TIPS. It found higher one-year survival without liver transplant and fewer hospital days in the TIPS group. 24 studies (14 retrospective, 10 prospective) measured spontaneous bacterial peritonitis (SBP) (defined as either growth on culture or polymorphonuclear count ≥250 cells/mm³) identified during routine ascitic fluid analysis of asymptomatic outpatients. The pooled prevalence was 2.31% (95%CI 1.48% to 3.15%, I²=84.7%) (Fig. 1). Four observational studies compared paracentesis by non-medical providers against paracentesis by physicians, finding no safety difference, but three did not report summary statistics or the statistical tests used, if any.

441

Severity of hepatic steatosis is associated with atherosclerotic cardiovascular disease and type 2 diabetes mellitus

Oyekoya Ayonrinde^1,2,3, Leon A Adams¹, Trevor Mori¹, Phillip Melton^1,4, John Olynyk^2,3, Marilyn Zelesco², Andrea Mould², James Fiori², Lawrence Beilin¹, Girish Dwivedi^1,2,3, Frank Sanfilippo^1,5 and Christopher Welman^2,5

¹The University of Western Australia, Perth, Australia; ²Fiona Stanley Hospital, Murdoch, Australia; ³Curtin University, Bentley, Australia; ⁴University of Tasmania, Hobart, Australia; ⁵Royal Perth Hospital, Perth, Australia

Background and Aim: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality in people with steatotic liver disease (SLD). We aimed to examine associations between the severity of SLD and carotid intima media thickness (cIMT) as a measure of carotid atherosclerosis.

Methods: Middle-aged and older adults participating in a cross-sectional follow-up of the Raine study in Perth, Australia, had comprehensive liver assessments using FibroScan® with controlled attenuation parameter (CAP) and transient elastography (TE), anthropometry, fasting blood tests, blood pressure and carotid artery ultrasound. SLD was defined by CAP ≥275 dB/m. Severity grades of hepatic steatosis were determined as CAP <275 dB/m = no steatosis (S0), 275-300 dB/m = grade 1 steatosis (S1), 301-331 dB/m = grade 2 steatosis (S2), and >331 dB/m = grade 3 steatosis (S3). cIMT ≥1.0 mm was considered to represent carotid atherosclerosis. Remnant lipoprotein cholesterol, representing atherogenic dyslipidaemia, and the homeostasis model for insulin resistance (HOMA-IR), were calculated. Carotid artery sonographers were blinded to the results of the CAP and TE assessments. We examined the relationship between the severity of hepatic steatosis, cIMT, type 2 diabetes mellitus (T2DM), and other cardiometabolic risk factors.

Results: Three hundred and thirty-one predominantly Caucasian adults with mean (SD) age 60(7) years had liver assessments. During the same attendance, 132 also had a B-mode carotid artery ultrasound. Overall, 26% had SLD (38% male and 22% female, p=0.45), 6.0% grade 3 hepatic steatosis (7.6% male and 4.8% female), while 25% had carotid atherosclerosis (39% male and 16% female, p=0.006). Those with carotid atherosclerosis were older (66.1 [5.9] vs. 63.7 [5.2] years), had higher body weight (87.0[13.7] vs. 76.3[14.6] kg), waist circumference (102.7[12.0] vs. 94.2[13.5] cm), body mass index (29.8[4.6] vs. 27.7[4.0] kg/m2), and more severe hepatic steatosis (CAP 261[222-284] vs 238[207-267] dB/m), p<0.05 for all. Carotid atherosclerosis was associated with higher serum glucose (5.5[1.7] vs. 5.0[0.8] mmol/L), lower high density lipoprotein cholesterol (1.4[0.4] vs. 1.5[0.4] mmol/L) but similar low density lipoprotein cholesterol (3.1[1.2] vs. 3.2[1.0]) mmol/L and remnant lipoprotein cholesterol (0.6[0.3] vs. 0.5[0.3] mmol/L). Using multivariable logistic regression analysis, older age (OR 1.11, 95% CI 1.02-1.21, p=0.02), male sex (OR 3.41, 95% CI 1.28-9.06, p=0.01) and a diagnosis of grade 3 hepatic steatosis (OR 9.28, 95% CI 1.29-66.67, p= 0.03) were associated with carotid atherosclerosis after adjusting for a diagnosis of type 2 diabetes mellitus (OR 4.54, 95%CI 0.93-22.12, p=0.08), central obesity (OR 2.97, 95%CI 0.85-10.34, p=0.06), remnant lipoprotein cholesterol (OR 2.36, 95%CI 0.46-12.03, p=0.30), and liver stiffness measurement (OR 0.98, 95%CI 0.64-1.52, p=0.94). Fasting blood HOMA-IR and glucose levels were positively correlated with severity of hepatic steatosis, and increased with increasing severity of hepatis steatosis. Severe (grade S3) steatosis was the only variable that was significantly associated with a diagnosis of type 2 diabetes mellitus (OR 4.02, 95% CI 1.09-14.82, p=0.04), after adjusting for age, sex, central obesity, remnant lipoprotein cholesterol, and liver stiffness (none of which was associated with type 2 diabetes in this model, p>0.05).

445

The role of adjuvant therapy in HCC treated with curative intent ablation: a step too far?

Natalie Commins, Rohit Gupta, Lucy Vaux, Roger Wilson, Jonathan Langton, Andrew Sloss, Tehara Wickremeratne, Brooke Gaggin and James O'Beirne

Sunshine Coast University Hospital, Birtinya, Australia

Background and Aim: The IMBRAVE050 study demonstrated improved recurrence-free survival (RFS) in patients with high-risk hepatocellular carcinoma (HCC) receiving adjuvant atezolizumab and bevacizumab post curative treatment (ablation or liver resection) compared to active surveillance. Resection was the predominant curative treatment in the IMBRAVE050 cohort, and the majority of patients were of Asian background with chronic liver disease (CLD) secondary to Hepatitis B infection. This differs from the Australian context, where the majority of patients undergo microwave ablation (MWA), and the prevalence of Hepatitis B-associated CLD is much lower. This study aimed to explore the demographics, prevalence and outcomes of patients with high and low-risk HCC using the IMRAVE050 protocol. The primary outcomes were RFS and OS in the high and low-risk cohorts undergoing MWA or liver resection.

Methods: The study design was a retrospective cohort study over a 5-year period between 2019 to 2024. The inclusion criteria were patients over the age of 18, first diagnosis of HCC, and curative intent treatment with either MWA or liver resection. Patients were risk-stratified into high-risk and low-risk groups according to the IMBRAVE050 criteria. Statistical analysis was completed using the Wilcoxon signed rank and Kaplan-Meier method.

Results: 52 patients met the inclusion criteria. The median age was 68 (IQR 60-74). The most common cause of underlying CLD was Hepatitis C (34.6%). The majority of patients had a single lesion (84.6%) and were Barcelona Clinic Liver Cancer (BCLC) Grade 0/A at time of diagnosis. The initial treatment was MWA in 76.9% (n=40) of patients. There were no procedure-related deaths. The majority of patients fulfilled high-risk criteria as defined by IMBRAVE050 (55% undergoing MWA and 75% undergoing liver resection). The majority of patients were followed up to 1 year (90%). 1-year RFS in patients who underwent liver resection was 77.8% in high-risk and 100% in low-risk patients, respectively. In patients who underwent MWA, 1-year RFS was 90% in the high-risk cohort and 66.7% in the low-risk cohort (Figure 1) p=NS. Overall Survival at 1-year was 100% in all cohorts.

Conclusion: Applying the IMBRAVE050 risk stratification to Australian patients undergoing curative treatment for HCC did not correlate with a significant difference in either RFS or OS at 1 year or across the study period. This is likely due to the inherent differences in the Australian population of patients diagnosed with HCC compared to the IMBRAVE050 cohort. Further research is needed in this context to determine which patients may benefit from adjuvant therapy.

450

Enterovirus-induced severe acute hepatitis post-rituximab treatment: a case report

Natalie Hung and Karen Waller

Concord Repatriation General Hospital, Concord, Australia

Introduction: Enterovirus is an exceedingly rare cause of hepatitis in adults and is rarely included in viral hepatitis testing. With the increasing use of rituximab, a B-cell depleting therapy, unique clinical presentations are emerging. This report presents a compelling case of severe enterovirus-induced hepatitis in a patient following rituximab treatment.

Case report: A 42-year-old male patient presented with a one-week history of intermittent fever, nausea, and headache, with blood tests showing acute hepatitis. There was no significant alcohol or drug use. Past medical history included classic hairy cell leukemia, treated with cladribine and four, weekly-administered doses of rituximab (completed 3-4 months prior). Regular medications were prophylactic trimethoprim/sulfamethoxazole and valaciclovir; Shingrix vaccine was administered 1 week prior. Examination revealed no signs of chronic liver disease. Liver function tests showed elevated AST 477 U/L, ALT 1065 U/L, GGT 72 U/L, ALP 169 U/L but normal bilirubin 11 μmol/L. Serology for common causes of viral hepatitis (hepatitis A, B, C, and E, Epstein-Barr virus, cytomegalovirus) were negative. Autoimmune markers and other bloods for liver disease were unremarkable. Imaging returned benign. Over three weeks, his liver function tests fluctuated (ALT range 864-1750 U/L), with ongoing intermittent fevers. Liver biopsy showed a diffuse T-lymphocyte infiltrate involving the sinusoids, without clonality. Positron emission tomography scan showed no significant glucose uptake. Further infection screening including biopsy immunohistochemistry for human herpes virus (HHV)-8 and varicella zoster virus, stool and respiratory viral polymerase chain reaction (PCR) panels, and bloods for syphilis, leptospirosis, Q fever, adenovirus, herpes simplex virus, HHV-6, HHV-7 and HHV-8; all returned negative. Given no improvement, prednisolone 1mg/kg was given to treat a possible inflammatory drug reaction. However, after 3 days the patient developed a high fever, increased ALT (3776 U/L) and bilirubin (43 μmol/L), and steroids were ceased. At this stage, a dedicated stool PCR for enterovirus returned positive, and blood enterovirus PCR testing was positive. After multidisciplinary discussion, the diagnosis of severe enterovirus-related hepatitis was made. The patient was treated with Australian intravenous immunoglobulin (IVIG), leading to decline in liver enzymes and negative blood enterovirus PCR. Now 12 weeks post-presentation, the patient continues on IVIG fortnightly, with latest ALT 185 U/L.

Conclusion: This case highlights a rare presentation of severe enterovirus hepatitis in a patient with recent rituximab administration, with unusual biopsy findings and response to IVIG. Clinicians faced with unexplained hepatitis in patients with acute hepatitis post-rituximab must consider rare infections after common aetiologies have been excluded.

452

Liver Supportive Care – utilisation of palliative care and care coordination to improve outcomes for liver disease patients

Asma Baig¹, Sara Qayyum¹, Melinda Tam¹, Christopher Sewell¹, Hannah Lam¹, Andrew Tang¹, Vi Nguyen¹, Phillip Chang¹, Gordon Park¹ and Cameron Gofton^1,2,3

¹Royal North Shore Hospital, St Leonards, Australia; ²l,Storr Liver Centre, Westmead Hospita, Westmead, Australia; ³Westmead Institute for Medical Research, The University of Sydney, Westmead, Australia

Background: Advanced liver disease (ALD) poses significant challenges, including high symptom burden, frequent hospital readmissions, and complex care needs for patients. Traditional models delay palliative care until end-of-life stages or End-Stage Liver Disease (ESLD), often missing opportunities for earlier intervention, holistic approach to care and ‘unmet needs’ that could improve patient outcomes.

Aim: The Liver Supportive Care program aimed to enhance the quality of life and health outcomes for patients with ALD with early integration of palliative care to manage symptoms, reducing hospital readmissions, and providing comprehensive, patient-centred care through a multidisciplinary approach.

Results: Since June 2023, the program has reduced 30-day readmissions from 42% to 12.12% and 90-day readmissions from 50% to 15.15%. With a clear discharge follow-up pathway, the program has reduced the average length of stay in hospital from 16.1 days (statewide) to approximately 4.6 days (within RNSH). Additionally, 48% of patients received early palliative care reviews, with 25% referred to community palliative care for ongoing management. Of the 18% of patients that have deceased since being on the program, 50% of the patients were known to community palliative care teams and care was escalated to a palliative care unit for End-of-Life care (EOLC) or to an acute hospital for management of reversible causes. The program has achieved significant cost savings and improved patient outcomes by reducing readmission rates and improved linkage to community services, as appropriate.

Conclusion: The Liver Supportive Care program demonstrates that early integration of palliative care and a multidisciplinary approach significantly improve health outcomes and reduce hospital readmissions for ALD patients. Its sustainable, scalable model offers a valuable framework for transforming chronic disease management, ensuring comprehensive and compassionate care that aligns with patient needs and healthcare efficiency.

460

Achieving abstinence: Prescribing AUD medications in ARLD

Janis Fernandes, Mikaela Daniells, Lucy Vaux, Andrew Sloss, Tehara Wickremeratne, James O'Beirne and Rohit Gupta

Sunshine Coast University Hospital, Birtinya, Australia

Background and Aim: Alcohol-related liver disease (ARLD) is the most common cause of liver cirrhosis; despite the clear benefit of abstinence this remains challenging to achieve. Pharmacotherapeutic options for the treatment of alcohol use disorder (AUD) are available, however, these medications are only sporadically prescribed by hepatologists. This paper aims to establish the utility of specific AUD pharmacotherapies prescribed to patients with ARLD within our local population.

Methods: A retrospective intention-to-treat cohort study of AUD medication prescribed through the hepatology clinic or on discharge from the inpatient hepatology unit over the last 24 months was completed. The primary outcome was alcohol abstinence at 6 months +/- 2 months with a secondary outcome of reduced alcohol consumption at 6 months +/- 2 months. Each patient was prescribed either acamprosate, baclofen, gabapentin or naltrexone. Patients were additionally offered behavioural and psychological support either through referral to Alcohol and Other Drugs Service (AODS), hepatology nurse review through the hepatology alcohol reduction program or psychotherapy through the hepatology clinic psychologist. To calculate the absolute risk reduction with pharmacotherapy, the UKMAS study was utilised (Chick et al, 2000). The result from the UKMAS study showed in the placebo/psychotherapy group the abstinence rate was 11% and a reduction in a further 6% of patients.

Results: The cohort comprised 87 patients with 81% with cirrhosis (57% Child’s Pugh A). The mean age was 54 years. There were 40 males and 47 females. The primary outcome of abstinence was achieved in 21% of patients with 56% achieving the secondary outcome of reduced alcohol intake as outlined in Figure 1. The absolute risk reduction for all medications to achieve abstinence was 8.5% with the NNT=12. Notably, in the follow-up period many patients experienced adverse effects and ceased medication while six patients did not commence treatment.

461

The clinical characteristics and outcomes of patients diagnosed with hepatocellular carcinoma in Far North Queensland, Australia

Harendran Elangovan

Princess Alexandra Hospital, Brisbane, Australia

Background and Aims: To determine the factors predicting survival in individuals diagnosed with hepatocellular carcinoma (HCC) in a region of remote Australia where First Nations Australians represent 17% of the population and reside in communities with chronic hepatitis B virus (HBV) infection prevalence of up to 6%.

Methods: A retrospective cohort study of individuals diagnosed with HCC in Far North Queensland, Australia between Jan 2014, and Sep 2021. The study’s primary outcome was overall survival.

Results: There were 169 individuals diagnosed with HCC during the study period, their mean (95 % confidence interval (CI)) age was 65 (64-67). First Nations Australians were not over-represented (15 % of the cohort). The most common risk factors for liver disease were alcohol use disorder (66 %), chronic hepatitis C virus (HCV) (47 %) and metabolic dysfunction (24 %). HBV-related HCC was a less common (10 %) aetiology, and there were no reported cases in Aboriginal Australians. The mean (95 % CI)) survival in the cohort was 421 (304-570) days. In multivariate analysis, death was more common in individuals with Child-Pugh C cirrhosis (hazard ratio (HR) (95 % CI)): 3.63 (2.20-5.99), p < 0.0001) and individuals with HBV infection (HR (95 % CI): 2.17 (1.25-3.77), p = 0.006). Individuals with chronic HCV infection were less likely to die (HR (95 % CI): 0.46 (0.31-0.69), p < 0.0001). Only 24 % of the cohort was participating in HCC surveillance at time of diagnosis despite most patients having guideline-recommended indications for screening; individuals participating in HCC surveillance were less likely to die (HR (95 % CI): 0.54 (0.33-0.90), p = 0.02).

Conclusions: HCC surveillance is associated with improved survival, but uptake in the region is suboptimal and contributes to the very poor outcomes. The absence of HBV-related HCC in Aboriginal individuals despite a high community prevalence of HBV infection suggests that HBV genotype might be employed to inform optimal HCC surveillance strategies in this remote region of Australia.

462

Ethnicity-based differences in severity of hepatic steatosis in patients with viral hepatitis

Zhi Tan¹, Oyekoya Ayonrinde^1,2,3, Crystal Connelly¹, Marcelle Scagliotta¹ and Wendy Lam¹

¹Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, Australia; ²Medical School, University of Western Australia, Crawley, Australia; ³Faculty of Health Sciences, Curtin University, Bentley, Australia

Background and Aim: Controlled Attenuation Parameter (CAP) is a useful point of care tool for hepatic steatosis assessment. Studies have shown that CAP values vary across different liver disorders, and are influenced by factors such as adiposity distribution, sex and age. Notably, ethnicity significantly impacts adiposity distribution. Therefore, we aimed to investigate associations between ethnicity and other demographic characteristics, and the severity of hepatic steatosis measured with CAP in patients with chronic viral hepatitis.

Methods: This is a single-centre study examining the distribution of CAP performed between October 2011 and January 2022 on adult outpatients with chronic viral hepatitis B (CHB) and C (CHC). Patient demographics (age, ethnicity and sex), type of viral hepatitis (CHB or CHC) and CAP score were recorded. CAP scores were performed by a hepatology nurse with experience of over 500 examinations, with a medium (M) or extra-large (XL) probe using a FibroScan model 502 Touch.

Results: We included 3202 CAP examinations on patients with a median age of 50 years, with 65% being male. Majority of the patients (65%, 2076 cases) had CHC. Most examinations (84%) were on non-Asian patients, with 511 (16%) examinations conducted on patients of Asian ethnicity. Among the Asian-born patients, the majority had CHB (90%). Mean CAP value in patients with CHC was significantly higher compared to CHB (253 vs 238dB/m, p<0.001). The mean CAP value among male patients was significantly higher compared to female (254 vs 236dB/m, p < 0.001). Further, the mean CAP value was lower among the Asian patients compared to non-Asian patients (237 vs 250dB/m, p <0.001). Within the viral hepatitis groups, there was no statistically significant difference between ethnicities. There was a positive correlation between age and CAP (Spearman rho 0.156, p <0.001).

464

Low testosterone levels are common in men with non-alcoholic fatty liver disease with and without hepatic fibrosis and cirrhosis

Ross Apostolov^1,2, Andrew Chen¹, Nirbaan Walia¹, Angus Patterson², Harris Siladi², Darren Wong^1,2, Mathis Grossmann^2,3 and Marie Sinclair^1,2

¹Department of Gastroenterology and Liver Transplant, Austin Health, Heidelberg, Australia; ²Department of Medicine, The University of Melbourne, Parkville, Australia; ³Department of Endocrinology, Austin Health, Heidelberg, Australia

Background: Low serum total testosterone (TT) has been associated with metabolic derangements including non-alcoholic fatty liver disease (NAFLD) in men, however the prevalence of low TT levels in men with NAFLD has not been well studied. Previous studies have reported an inverse relationship between TT levels and disease severity in men with NAFLD. This study aimed to prospectively determine the prevalence of low TT levels in men with NAFLD and to determine the impact of liver stiffness and presence of cirrhosis on TT levels.

Methods: This single-centre study prospectively measured fasting, early morning testosterone levels in men with traditionally defined NAFLD. A cut-off of 12nmol/L was used to define low TT and 230pmol/L for calculated free testosterone (cFT). Univariable and multivariable logistic regression was used to determine the effects of liver stiffness, as measured by transient elastography (Fibroscan®), and presence of cirrhosis on testosterone levels when adjusting for age, body mass index (BMI) and presence of type 2 diabetes (T2D).

Results: Testosterone levels were measured in 284 men with NAFLD. Patients had a median age of 51.9 (interquartile range (IQR) 42.2-64.7), BMI of 30.9 (IQR 27.6 – 34.8), ALT of 51 IU/L (IQR 36.5-77.5), TT level of 10.9 nmol/L (IQR 8.1 – 13.4), SHBG level 27 (IQR 17 – 39), cFT level of 234, (IQR 178 – 294), liver stiffness score of 6.4 kPA (IQR 5.1 – 9.3) and HbA1c of 6.1 (IQR 5.6 – 6.9). Cirrhosis was present in 53/284 (18.7%), of whom 79.3% were Child Pugh A, and T2D in 114/284 (40.1%) patients. A total of 174/284 (61.3%) patients had low TT levels and 132/284 (46.5%) patients had low cFT levels. Univariable logistic regression demonstrated that increasing liver stiffness and presence of cirrhosis were associated with low cFT levels (OR=1.038, 95% CI:[1.009, 1.074], p < 0.028 and OR=2.978, 95% CI:[1.602, 5.726], p <0.001, respectively). No relationships between liver stiffness or cirrhosis and TT levels were observed on univariable analysis. Multivariable analysis showed neither liver stiffness nor cirrhosis had any significant impact on TT or cFT levels when adjusting for age, BMI and T2D.

Conclusions: Low serum TT and cFT levels were highly prevalent in men with NAFLD both with and without liver fibrosis and cirrhosis. Higher liver stiffness and presence of cirrhosis were not independently associated lower TT or cFT levels, although our cohort had mainly compensated cirrhosis. Future studies are needed to determine the effects of testosterone therapy on improving liver outcomes in men with NAFLD.

469

A case of vanishing hepatocellular carcinoma

Natalie Hung¹, Neha Chandrasekar¹, Osamah Al-obaidi¹, Karen Waller¹, Kenneth Lee², Caroline Fung², Jessica Yang¹ and Emily He¹

¹Concord Repatriation General Hospital, Concord, Australia; ²NSW Health Pathology, Sydney, Australia

Introduction: Hepatocellular carcinoma (HCC) is a primary liver tumour that typically occurs in cirrhosis and is the third most common cause of cancer-related mortality worldwide. Whilst rare, cases of spontaneous HCC regression has been documented. Herein, we describe an interesting case of a 76-year-old female with imaging and biopsy proven HCC who underwent spontaneous regression.

Case report: The patient was referred for assessment due to abnormal liver function tests (LFTs) on a background of known hepatitis C virus (HCV) and previous hepatitis B virus (HBV) exposure. Pre-treatment Fibroscan measured 11.6 kPa. Following treatment with sofosbuvir, velpatasvir, and voxilaprevir after an initial failure with sofosbuvir and velpatasvir, she achieved sustained virologic response (SVR), and LFTs normalised. Following SVR, HCC surveillance continued and approximately 2 years later, a new segment 8 lesion was found on both triple-phase CT and MRI. Alpha Fetoprotein (AFP) was normal at 1.7 ng/ml. The atypical appearance of the lesion with arterial enhancement (but no venous portal washout) on CT led to biopsy of the lesion 2 weeks later, confirming well-differentiated HCC on histopathology. After diagnosis, the patient disengaged with medical care and declined further treatment, citing trauma of having been a carer for a family member with HCC. After ongoing attempts to reach her, she agreed to have repeat imaging to reassess her disease 18 months after initial diagnosis. Surprisingly, it revealed disappearance of the lesion. Her case was reviewed by the HCC multidisciplinary team and the consensus was to continue monitoring. At this time, the patient again disengaged with medical care. 2 years later, the patient was hospitalised due to advanced Alzheimer’s disease and multiple falls. A repeat CT multiphase liver again found no evidence of the original or any new lesions. Furthermore, liver function tests and AFP level were normal.

Conclusion: Spontaneous regression of HCC is rare. Meta-analysis of cases estimates incidence as 0.41%. Given scarcity of publications, it is difficult to ascertain causes of cure. Proposed factors include ischaemia, systemic inflammatory response and alcohol abstinence. This patients’ imaging showed no abnormalities in her hepatic vasculature at the time of diagnosis. There were no documented episodes of hypotension to cause hepatic ischaemia, nor systemic febrile illness to suggest activation of a systemic inflammatory response. It is therefore difficult to propose mechanisms for this case of regression. However, alteration in immune surveillance in response to the clearance of HCV in the setting of past HBV exposure may play a role. This case demonstrates that HCC can undergo spontaneous regression. Mechanisms that affect this are not well understood. Further investigation into mechanisms of spontaneous tumour regression can help guide development of future treatment options for HCC.

482

An unusual cause of granulomatous hepatitis - an important differential following a global outbreak

Adam I Kaplan^1,2, Luke J Vlismas^1,2 and Glenn Hawken¹

¹Department of Gastroenterology and Hepatology, Gosford Hospital, Gosford, Australia; ²School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia

Introduction: Granulomatous hepatitis is a diverse clinical entity characterised by the presence of granulomas in the liver, which form as a result of inflammatory reactions in response to noxious stimuli (1). There are many aetiologies, most commonly sarcoidosis, tuberculosis, primary biliary cirrhosis, and drug induced liver injury. We present an unusual cause of granulomatous hepatitis resulting from a global outbreak of nosocomial disease, which posed a challenging diagnostic dilemma.

Case report: A 67-year-old female was referred to gastroenterology with a six-week history of upper abdominal discomfort, nausea, anorexia, fatigue, and 15kg weight loss. Abdominal examination was unremarkable. Past medical history included a bioprosthetic aortic valve replacement (AVR) six-years prior for bicuspid aortic valve related stenosis. Her only regular medication was aspirin, with no over-the-counter or complementary medicines. Liver enzymes were deranged in a cholestatic pattern: alkaline phosphatase (ALP) 1332, gamma-glutamyl transferase (GGT) 425, aspartate aminotransferase (AST) 117, alanine aminotransferase (ALT) 122, and bilirubin 19. Autoimmune panel, viral screen, and tumour markers were all non-contributory, and multiple modalities of imaging including magnetic resonance cholangiopancreatography showed no hepatopancreatobiliary abnormalities. Endoscopic examination was unremarkable macroscopically, but gastric biopsy identified Helicobacter pylori gastritis, for which she received clarithromycin based triple therapy without symptom improvement. Liver biopsy was performed due to persistence of symptoms and liver function derangement, with tertiary histology review identifying severe granulomatous hepatitis. There were many differentials considered, but no definite diagnosis made initially. Her General Practitioner commenced prednisone for a presumed inflammatory aetiology, following which she developed fevers and night sweats and was hospitalised. Infectious diseases (ID) were consulted, with further serology and transthoracic echocardiogram undertaken, which were unremarkable, and she was discharged home. 24-hours after discharge, a blood culture became positive for Cutibacterium species, which was suspected to be a skin contaminant, however outpatient transoesophageal echocardiogram was arranged due to the ongoing diagnostic dilemma and her previous AVR, which identified an aortic valve root abscess. Urgent AVR revision surgery was performed, and Mycobacterium chimera was identified on operative samples and mycolytic blood culture. Prednisone was quickly weaned to cessation. Liver enzymes improved following surgical source control, most recently measuring: ALP 143, GGT 183, AST 34, ALT 32, and bilirubin 7. She remains on long term anti-mycobacterial treatment guided by ID. Retrospective investigation revealed that her original AVR surgery was performed during M chimaera heater-cooler units (HCU) exposure in an Australian hospital.

Discussion: M chimaera is a non-tuberculous mycobacterium within the Mycobacterium avium complex. Since 2013, there has been a global outbreak of over 100 M chimaera cases linked to contaminated HCUs used in cardiothoracic surgery (2, 3). Reported cases of M chimaera hepatitis cases are rare, though are associated with a high mortality of up to 71% despite aggressive antimicrobial therapy (4). Diagnosis of disseminated M chimaera infection has proven difficult due to a long latency period, typically non-specific presentation of disease, intermittent bacteraemia, and often normal echocardiography in early infection. Notably, cases are commonly misdiagnosed as sarcoidosis due to granulomatous involvement. Treatment involves prolonged antibiotic therapy, with early surgical management and source control vital for successful therapy (5).

Conclusion: Following the global outbreak of contaminated HCU units, this case highlights the potential for M chimaera granulomatous hepatitis in patients with a history of cardiothoracic surgery and demonstrates the importance of surgical source control and multidisciplinary management to optimise patient outcomes.

References

1. Coash, M, et al. J Formos Med Assoc. 2012; 111(1): 3-13.

2. Ingen, J, et al. Lancet Infect Dis. 2017; 17(10): 1033-41.

3. Kohler, P, et al. Eur Heart J. 2015; 36(40): 2745-53.

4. Shafizadeh, N, et al. Am J Surg Pathol. 2019; 43(2): 244-50.

5. Kasperbauer, SH, et al. Clin Infect Dis. 2018; 68(7): 1244-50.

494

Significant gaps in the hepatitis B cascade of care impact survival in hepatitis B-related hepatocellular carcinoma (HCC): a longitudinal cohort study of incident HCC cases in Victoria, Australia

Dina Moussa^1,2,3, Joan Ericka Flores^1,3, Thai Hong¹, Zina Valaydon⁸, Brett Knowles^1,3, Adrian Fox^1,3, Tom Sutherland^1,3, Ashu Jhamb¹, Tim Papaluca¹, Rohit Sawhney^3,4,7, Amanda Nicoll^4,7, Stephen Bloom^4,7, Stuart Roberts^4,5, William Kemp^4,5, Ammar Majeed^4,5, Marie Sinclair^3,6, Gauri Mishra⁹, Siddharth Sood^10,11, Diana Lewis¹⁰, Marno Ryan^1,3, Alexander Thompson^1,3 and Jessica Howell^1,2,3,4

¹St Vincent's Hospital Melbourne, Fitzroy, Australia; ²Burnet Institute, Melbourne, Australia; ³University of Melbourne, Melbourne, Australia; ⁴Monash University, Clayton, Australia; ⁵Alfred Health, Melbourne, Australia; ⁶Austin Health, Heidelberg, Australia; ⁷Eastern Health, Box Hill, Australia; ⁸Western Health, Footscray, Australia; ⁹Monash Health, Clayton, Australia; ¹⁰Northern Health, Epping, Australia; ¹¹Melbourne Health, Parkville, Australia

Background and Aim: Hepatitis B (HBV) is a major cause of hepatocellular carcinoma (HCC) in Australia, despite availability of effective, subsidised treatment that reduces HCC risk. In this cohort study, we aimed to describe the clinical characteristics, cascade of HBV care and clinical outcomes among people with HBV-related HCC in Victoria, Australia.

Methods: We conducted a multi-centre retrospective (1^st January 2018 to 31^st Oct 2021) and prospective (1^st Nov 2021 to 31^st Oct 2022) cohort study of all incident HCC cases diagnosed across six tertiary health networks with specialist HCC services in Melbourne. HCC cases were identified using clinical HCC databases, cross-referenced with HCC multidisciplinary team (MDT) meeting discussions and electronic medical records. Primary outcome was number (proportion) incident HBV-related HCC; secondary outcomes were number (proportion) HBV-HCC receiving guideline-based treatment and surveillance, and survival time (months) since HCC diagnosis. Bi-variable analysis was performed using chi square test. Multivariable logistic regression modelling was used to determine variables associated with HBV treatment and surveillance uptake, respectively. Cox proportional hazards modelling was used to identify variables associated with survival from HCC diagnosis.

Results: 1203 incident HCC cases were identified, of which 219 (18.2%) were due to HBV. Over time, both the number and proportion of HCC cases due to HBV declined from 24% (N=52) in 2019 to 15% (N=33) in 2022. Most people with incident HBV- HCC were male (89%) and of Asian ethnicity (60%). Though most HBV-HCC occurred in people aged 56-75 years (61%), 25% were in young people aged 36-55 years. Compared to people with HCC due to other aetiologies, people with HBV-related HCC were more likely to have a family history of HCC (7% vs 1%, p<0.001), but were less likely to have other risks for chronic liver disease, such as alcohol misuse (23% vs 54%, p<0.001), type 2 diabetes (28% vs 39%, p=0.003) or obesity (6% vs 15%, p=0.001).

Cascade of HBV care: HBV status was known in all HBV-HCC cases at time of HCC diagnosis. 64% (141/219) had cirrhosis; 26% (57/ 141) were first diagnosed with cirrhosis at HCC diagnosis. 60% of people with HBV-HCC (121 of 203 with available data) were eligible for HBV treatment at the time of HCC diagnosis, yet 27% (22/121) were not on treatment. On multivariable analysis, being referred from primary care (adjOR 0.18, 95% CI 0.03-0.96, p=0.04) and being admitted to hospital at the time of HBV-HCC diagnosis (adjOR 0.09, 95% CI 0.02-0.34, p<0.001) were associated with not receiving guideline-based HBV treatment. 92% (201/219) of people with HBV-HCC were eligible for surveillance at the time of HCC diagnosis. Of these, 46% (N=92) were enrolled in surveillance (at least one surveillance ultrasound <12months of HCC diagnosis), compared to 38% of those with non-HBV related HCC (323/851; p=0.03). 65% (72/103) of those referred by specialist hepatology services were enrolled in surveillance, compared to 25% (21/91) of those referred by primary care and non-liver specialists (p<0.001).

Survival: Crude median survival from time of HCC diagnosis was longer among those with HBV compared to non-HBV HCC (50.7 mths compared to 32.2 mths; p<0.001). A greater proportion of HBV-HCC were diagnosed at early BCLC 0/A stage (58% compared with 45%, p<0.001) and therefore received curative therapy compared to non-HBV related HCC (46% compared to 33%, p<.001). On multivariable analysis, factors associated with greater mortality in people with HBV- HCC were low performance status (HR 1.53, 95% CI 1.14-2.05, p=0.004), alcohol misuse (HR 2.30, 95% CI 1.29-4.10, p=0.005) and advanced BCLC stage at diagnosis (HR 2.21, 95% CI 1.70-2.88, p<0.001). Attending a liver specialist service, being enrolled in surveillance and being on HBV treatment were all associated with early BCLC stage HCC at diagnosis in people with HBV-HCC (all p<0.001).

Conclusion: The proportion of incident HCC cases due to HBV is reducing in Victoria, however a significant proportion of people with HBV-related HCC are not receiving guideline-based care, which adversely impacts survival. Greater investment in education and training in HBV care, coupled with a national system to support HCC surveillance are urgently needed.

495

Surveillance and MDT improves mortality at 24 months in hepatocellular carcinoma cases at a tertiary centre with a large regional referral base

Michael Christmas¹, Janny Huangfu¹ and Purnima Bhat^1,2

¹The Canberra Hospital, Canberra, Australia; ²Australian National University, Canberra, Australia

Background and Aim: The rates of Hepatocellular Carcinoma (HCC) are growing but outcomes remain poor. Improved outcomes rely on early diagnosis and optimal management in a multi-disciplinary team (MDT) setting. Systematic surveillance in a tertiary hospital setting is currently the optimal method of early detection, a challenge for regionally located patients. Previous studies have suggested inferior HCC outcomes for the geographically challenged¹. We present the outcomes of patients treated for HCC in a tertiary metropolitan hospital liver clinic with a large regional referral base covering over a million patients.

Methods: A single centre retrospective analysis of prospectively collected data from patients with HCC. A database was acquired by two methods: 1. ICD code search from the hospital medical records of patients with a diagnosis of HCC between the years of 2016 to 2022; 2. Prospectively collected data from liver tumour MDT. Demographic data, tumour characteristics, treatment and outcomes were recorded from date of diagnosis retrospectively to first encounter and prospectively to 2022. The χ² test was used to compare groups. A P < 0.05 was considered the level of significance.

Results: From 2016-2022 a total of 170 cases of HCC were identified: 74.7% male, average age 65.5 ± 9.8 years, with a metropolitan: regional ratio of 117:53. A total of 9 (5.3%) were of First Nations origin. Most (88.2%) of the cases had cirrhosis, many of patients had multiple aetiologic risk factors and the most common aetiology was hepatitis C – at least a cofactor in 52.7% of cases. Alcohol and Metabolic-Dysfunction Associated Steatotic Liver Disease comprised most of the rest. A significant portion (46.8%) of the cases were found within 12 months of their diagnosis of cirrhosis. 29.4% of the cases had multiple (>3) lesions at diagnosis with 48.2% of lesions >30mm at diagnosis. 77.6% of the cohort was discussed in the liver tumour MDT. As found previously, discussion at MDT offered improved survival at both 6 and 24 months (p=0.001). The average time to intervention from identification of the lesion was 100 ± 48 days. Overall, 6-month and 24-month survival rate was 22.6% and 45.8%, respectively. The earlier stage the disease (BLCL 0 and A) was identified, conferred a significant mortality benefit at 24 months: 28.7% compared to later stages (BLCL B, C and D) 64.0%. Notably, no patients captured had liver transplantation. The best survival was seen in the lobectomy treatment group: 94.1% survival rate at 24 months. TACE was offered to around 40% of patients, with outcomes similar to resection at 6-months, but significantly inferior at 24 months. Surveillance led to earlier diagnosis: lesions were significantly smaller and fewer, were more likely to be offered curative therapy, reflected in higher 6-month 24-month survival rates for patients under surveillance. However, only 28.7% of HCC patients were on a surveillance program. Our rural patients were equally likely to be surveilled, presented similarly to urban patients, and had improved mortality outcomes at 6 months, which were not seen at 24 months. They were more likely to be offered curative therapy despite disease parameters being similar to metropolitan patients (p=0.009).

Conclusion: Patients living regionally can receive the same expert care in the management of HCC, which leads to improved patient outcomes. However, this analysis highlights the importance of early diagnosis of cirrhosis, surveillance, and expert involvement. A primary care, regional education and remote surveillance program should form part of the management plan of HCC on a national level.

Reference

1. Taye, BW, et al. Remoteness of residence predicts tumour stage, receipt of treatment, and mortality in patients with hepatocellular carcinoma. JGH Open. 2021 Jun 5; 5(7): 754-762.

498

Transjugular intrahepatic portosystemic shunt outcomes at a tertiary non-transplantation centre

Gary Zhang^1,2 and Oliver Duncan¹

¹Fiona Stanley Hospital, Murdoch, Australia; ²The University of Western Australia, Crawley, Australia

Background and Aim: Portal hypertension is associated with considerable morbidity and mortality. Transjugular intrahepatic portosystemic shunt (TIPS) represents a specialised therapeutic procedure in the management of portal hypertension related complications, particularly refractory ascites and variceal haemorrhage. We aimed to assess the selection of TIPS patients, success rate, complication rates, and survival outcomes at a single tertiary hospital in Western Australia.

Methods: Patients who underwent TIPS between the 1st January 2018 to 18th August 2023 were identified retrospectively from the Fiona Stanley Hospital (FSH) medical imaging database using the specific TIPS procedure code. The cohort was confirmed through a search of orders for the sole stents utilised for TIPS at FSH. Data were collected from electronic medical records, which including procedural reports, pathology results, clinic letters, clinical documentation, and multidisciplinary team meeting outcomes until the 1^st May 2024. The Kaplan-Meier method was used to analyse survival.

Results: A total of 33 patients underwent TIPS in the study period. The median age of TIPS insertion was 60 years (IQR 52-67), with 33.3% females. Liver cirrhosis was recorded in 28 patients (87.9%), with aetiologies including alcohol (36.3%), metabolic-dysfunction associated steatotic liver disease (MASLD) (30.3%), mixed alcohol and MASLD (9.1%), hepatitis B (6.1%) and hepatitis C (6.1%). The median Model for End-Stage Liver Disease score was 12 (IQR 9-15), and 86.2% were Child-Pugh B. The four patients (12.1%) with noncirrhotic portal hypertension had portal vein thrombosis (6.1%) or hepatic veno-occlusive disease (6.1%). Refractory ascites was the most common indication for TIPS (54.5%). Thirteen patients (39.4%) underwent emergency TIPS due to endoscopically uncontrollable variceal haemorrhage, most commonly oesophageal (24.2%). All TIPS were performed under general anaesthesia and using the polytetrafluoroethylene covered GORE® VIATORR® 8-10mm diameter stent. Initial TIPS stent deployment was successful in 30 patients (90.9%); with no reattempt in one patient with refractory ascites, and in two patients with duodenal varices haemorrhage, TIPS was successful three days later in one, while another died intraoperatively. The median pre-TIPS portosystemic gradient (PSG) reduced from 18mmHg (IQR 15-23) to 9mmHg (IQR 6-11) post-TIPS. Eleven of the 13 patients (84.6%) undergoing rescue TIPS for variceal bleeding had a reduction of PSG ≥20% or post-TIPS PSG of <12mmHg. Two patients were lost to follow-up. No patients received liver transplantation. Cumulative survival at 6 months, 1 year and 3 years was 81.8%, 75.8%, and 33.3%, respectively. Survival was significantly higher in patients with Child Pugh A and B score compared to Child Pugh C (p=0.028), and there was a trend to improved survival post-TIPS with MELD <18 compared to MELD ≥18 (p=0.063). Using the Freiburg index of post-TIPS survival (FIPS) score, the high-risk group (n=3) had significantly reduced survival compared to the low-risk group (6-month survival rates 0% versus 90%, respectively; p<0.001). Survival was not significant between age groups (≥65 versus <65 years; and ≥70 years versus <70 years) and renal impairment (p=0.417). In patients undergoing TIPS for refractory ascites, the median number of paracentesis pre-TIPS was 6 (IQR 3.5-7.5) compared to 0 post-TIPS. The median number of inpatient admissions pre-TIPS was 2 (IQR 1-3.5) compared to 1.5 (IQR 1-2) post-TIPS. Recorded perioperative mortality included one patient with duodenal varices haemorrhage who deteriorated intraoperatively before the TIPS stent was placed, and another with oesophageal varices haemorrhage died 2 days later with liver failure post-TIPS. Encephalopathy following TIPS was recorded in 16 patients (48.5%), with interventions including TIPS occlusion (n=6, median time to TIPS occlusion 7.5 months), TIPS reduction only (n=1), and splenorenal shunt embolization (n=1). Two patients developed recurrent ascites, with one undergoing TIPS dilatation. One patient developed rebleeding from oesophageal varices following Ella Danis stent removal and underwent TIPS revision with a longer stent.

Conclusion: This retrospective single centre study of TIPS insertion for non-urgent and urgent indications has demonstrated a technical success rate and survival outcome comparable to larger cohort studies. Encephalopathy was a common complication post-TIPS and the rate of TIPS occlusion and reduction was higher than previously published reports. The novel FIPS score demonstrated prognostic utility, and this score along with psychometric testing for encephalopathy should be used for risk-stratification. The results of this study should be incorporated into a state and nationwide TIPS registry to ensure quality standards for this specialised procedure.

501

Adenovirus-induced acute liver failure with features of haemophagocytic lymphohistiocytosis

Sudarshan Arvind and Aviv Pudipeddi

Concord Repatriation General Hospital, Concord, Australia

Introduction: Adenovirus is a rare cause of viral-induced liver failure, usually causing a mild self-limited illness. However, it can result in fulminant disease with end-organ failure in immunocompromised patients. Its association with secondary hemophagocytic lymphohistiocytosis (HLH) is uncommon and primarily reported in pediatric cases. We report the first known adult case of adenovirus-induced acute liver failure with HLH features.

Case report: A 63-year-old woman presented with a 1-week history of lethargy and fevers following 3 days of watery diarrhea, which had resolved by the time of presentation. There was no abdominal pain or focal infective symptoms. The patient’s medical history included rheumatoid arthritis, treated with methotrexate 15 mg weekly, hydroxychloroquine 400 mg daily, and rituximab infusions every 6 months. There was no significant alcohol or drug use. Physical examination revealed a temperature of 38.8°C with no signs of chronic liver disease. AST was 856 U/L, ALT 698 U/L, GGT 24 U/L, ALP 101 U/L, and bilirubin 15 μmol/L. WCC was 6.8 x 10^9/L and CRP was 205.2 mg/L. Synthetic function was abnormal with platelet count of 126 x 10^9/L, INR 1.6, and albumin 31 g/L. Imaging showed no abnormalities. Viral screen was negative for Hepatitis A, B, C, and E, Epstein-Barr virus, cytomegalovirus, herpes simplex virus type 1 and 2, and HIV. Autoimmune serology was negative. Blood and stool cultures were negative, but a respiratory viral swab returned positive for adenovirus. On day 4, AST rose to 11,378 U/L, ALT 4944 U/L, bilirubin 55 μmol/L, and INR 1.8. Ferritin was 89,351 μg/L, triglyceride level was 2.1 mmol/L, WCC was 3.8 x 10^9/L, and platelet count was 88 x 10^9/L. Concerns for HLH arose and dexamethasone was administered. Parvovirus IgM was negative and natural killer cell function was normal. Liver and bone marrow biopsies were performed on day 4. Liver biopsy showed extensive hepatocellular necrosis with marked lobular inflammation and scattered hepatocytes containing viral inclusions. Ultrastructural examination and PCR confirmed adenovirus. Bone marrow biopsy showed prominent histiocytes and haemophagocytosis. Early on day 5, the patient developed grade 1 encephalopathy and was planned for transfer to a liver transplant center. The encephalopathy worsened rapidly, requiring ICU admission with plans for Cidofovir and intravenous immunoglobulin therapy the same day. However, before this could occur, the patient passed away.

Conclusion: Acute liver failure due to adenovirus is rare. In immunocompromised patients, broadening the initial viral screen may be beneficial. Cidofovir has shown efficacy in treating adenovirus-induced liver failure, reducing mortality in some cases. This patient developed features of HLH, meeting several diagnostic criteria. This is the first reported case of adenoviral infection causing acute liver failure with HLH features.

506

A one-stop-shop for hepatitis C care in the community corrections population: the peer and nurse-led C No More study

Samara Griffin^1,2,3, Rebecca Winter^1,2,3, Jacinta Holmes^3,4, Bridget Reid³, Jane Dicka⁵, Anne Craigie³, Tim Papaluca^3,4, Bradley Whitton³, Amanda Callus⁵, Mark Belzer⁵, Margaret Hellard^1,2,6,7, Mark Stoove^1,2,8 and Alexander Thompson^3,4

¹Burnet Institute, Melbourne, Australia; ²Monash Univerity, Melbourne, Australia; ³St Vincent's Hospital Melbourne, Melbourne, Australia; ⁴Department of Medicine, University of Melbourne, Melbourne, Australia; ⁵Harm Reduction Victoria, Melbourne, Australia; ⁶Kirby Institute, University of New South Wales, Sydney, Australia; ⁷Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia; ⁸Australian Research Centre in Sex, Health and Society, La Trobe University, Melbourne, Australia

Background and Aim: In-prison hepatitis programs are successful but exclude individuals on community corrections orders such as probation or parole. The community corrections population is likely to have similar risk factors for HCV infection and similar barriers to accessing healthcare as the incarcerated population. This study evaluated the clinical efficiency of a same-day nurse and peer-led mobile model of care at community corrections offices in Melbourne, Australia.

Methods: The C No More study enrolled individuals within the vicinity of three metropolitan community corrections offices. Participants were recruited opportunistically by a peer worker. At enrolment, individuals were tested with point-of-care HCV antibody tests and, if positive, point-of-care HCV RNA tests. Participants with self-reported HCV antibody were reflexed to RNA testing. RNA positive participants were assessed for treatment initiation, and prescribed treatment by a nurse practitioner.

Results: Among 375 participants enrolled in the study, 138 (37%) were on community corrections orders. Of those enrolled, 92 (24%) were reflexed to RNA testing due to reported antibody positivity. Of 283 antibody tests conducted, 12(4%) were positive. Among the 104 people RNA tested, 23 (22%) were positive. Of these, 16 (69%) commenced treatment, 4 were in the process of commencing treatment, one was treated elsewhere, and 2 chose not to pursue treatment. Of those who commenced treatment, 8 completed treatment and 7 had been tested for and achieved SVR, one participant did not achieve SVR due to treatment nonadherence. Overall, the prevalence of HCV RNA positivity was 6% (23/375).

Conclusion: This study shows high rates of retention in care and treatment initiation, indicating that a mobile, same-day test and treat model is effective at providing hepatitis C care to the community corrections population. The level of engagement of community members in the vicinity of this clinic and the prevalence of current HCV infection indicates there is a need for hepatitis C care in these community hubs.

520

Impact of prior locoregional therapy on immunotherapy response in patients with advanced hepatocellular carcinoma

Khaliun Batkhurel and Lay Theng Gan and Robert Gibson and Mark Loewenthal and Randy Tjang

Gastroenterology Department, John Hunter Hospital, Newcastle, Australia

Background: There are many established locoregional therapies for early-stage hepatocellular carcinoma (HCC). Treatment options for large/advanced HCC are limited. We know the HCC microenvironment is heterogenous, impacting response to immunotherapy. There is now evidence to support neoadjuvant locoregional therapy (LRT) prior to immunotherapy to increase these tumours’ response to immunotherapy. The train of thought is LRT pre-immunotherapy results in local hypoxia, increasing vascular permeability, inducing damage-associated molecular patterns (DAMP), leading to enhanced antiangiogenic and antitumor immune response to immunotherapy. There is currently no set pathway or standardise role for neoadjuvant LRT prior to immunotherapy in real world practice.

Aim: We looked at our cohort of patients with advanced HCC who has received/receiving immunotherapy to determine if there is a difference in those who had received prior LRT, compared to those naïve to LRT.

Methods: We did a retrospective analysis of all our patients in Hunter New England Area who has had immunotherapy from July 2021 to March 2024. The immunotherapy of choice is atezolizumab (Atez) and bevacizumab (Bev). We looked at overall survival across the 2 groups: one group with prior LRT, and the other without any prior LRT. Neoadjuvant LRT is defined as: trans arterial chemotherapy (TACE), radiofrequency ablation (RFA), liver resection, selective beam radiotherapy (SBRT) and selective internal radiation therapy (SIRT) prior to getting immunotherapy.

Results: We identified 48 patients who had received Atez and Bev. Approximately half (23 of 46) received only immunotherapy, without prior LRT. Both groups have similar relapse free survival, approximately 200 days. Factors contributing to disease progression were more seen in patients with Child Pugh B (6 out of 8), macrovascular invasion (15 out of 23) and extrahepatic metastasis (11 out of 16). There appeared to be a survival advantage for patients with prior LRT in the first 20 weeks of therapy (Figure 1), but this effect is lost after that.

523

Locally acquired hepatitis E virus infection in Queensland

Jenna Coffman¹, Sophie Willemse¹, Cathal McGowan¹ and Olivia Williams²

¹Department of Gastroenterology, Cairns Base Hospital, Cairns, Australia; ²Communicable Diseases Branch, Queensland Public Health and Scientific Services, Queensland Health, Cairns, Australia

Introduction: Hepatitis E virus (HEV) is a non-enveloped, single-stranded RNA virus. Genotype 1 and 2 are usually transmitted via the faecal oral route due to contaminated water, while genotype 3 and 4 are zoonotic, transmitted to humans by eating undercooked meat mainly pork. Between 2015 and 2020 there have been 91 HEV isolates sequenced in Australia, the majority were genotype 1 and presumed to have been acquired overseas. Just over one third were genotype 3 with potential local acquisition in New South Wales. Queensland has previously only reported one locally acquired case of acute HEV-infection. Our goal was to determine locally acquired hepatitis E virus infection in Queensland.

Methods: We describe a case series of ten likely locally acquired HEV-infections in Queensland. We collected prospective data from the public health registry in the setting of the National Notifiable Surveillance System on the incidence of hepatitis E virus infection and performed a retrospective search for positive HEV serology (HEV IgM and HEV IgG) and HEV PCR at Pathology Queensland from January 2021 to December 2023. We documented history regarding overseas travel, exposure to wild animals and possible HEV-containing foods (mainly pork).

Results: We found ten cases of (recent) HEV-infection between January 2021 and December 2023. Six cases were confirmed by PCR and four had dynamic seroconversion indicative of an acute infection. Nine cases had had no interstate or overseas travel or visiting family members. One case had travelled to Thailand prior to presentation with an acute hepatitis. Five cases had consumed pig liver sausage (locally purchased), of those all had confirmed genotype 3 on HEV-PCR. In one case the only exposure identified was that of exposure to wild pig excrement in a local creek. Three cases had no clear precipitant to development of transient liver test abnormalities and positive HEV serology.

Conclusions: This is the first reported HEV outbreak in Queensland. In this case series there were nine cases of likely locally acquired HEV-infection, of which five had consumed pork liver sausage and one that had contact with wild pig excrement, and three cases without a clear mode of transmission. HEV is not routinely tested in Australia but should be considered in patients presenting with acute hepatitis or unexplained deranged ALT, especially when immunocompromised.

544

Survival outcome of patients with acute gastric variceal bleeding in Western Australia between 1999 and 2019: a retrospective cohort study

James Chen^1,2, Walid Abu Shawish^1,4, Andrew Chin¹, Madoka Inoue^1,3, Sharon Chen³, Tim Mitchell¹, Justin Chin¹, Wendy Cheng^1,2, Nick Kontorinis¹, Krish Ragunath^1,3 and Adam Doyle¹

¹Royal Perth Hospital, Perth, Australia; ²University of Western Australia, Perth, Australia; ³Curtin Universtiy, Perth, Australia; ⁴The Alfred Hospital, Melbourne, Australia

Background and Aims: Acute gastric variceal bleeding (GVB) is a life-threatening complication of portal hypertension with high mortality rates. Despite endoscopic glue injection therapy (EGI), re-bleeding occurs in over one-third of patients. Limited data from large observational studies exist on re-bleeding risk factors, long-term survival, and the need for rescue therapies like transjugular intrahepatic portosystemic shunt (TIPS). This study aimed to evaluate survival outcomes following EGI within 24 hours of an index GVB presentation and identify predictors of re-bleeding and TIPS requirement.

Methods: A retrospective cohort study was conducted on patients aged ≥18 years who underwent emergency endoscopy within 24 hours for an index acute GVB presentation between 1999 and 2019 at four tertiary hospitals in Western Australia, with follow-up until July 2022. Patients were identified through endoscopy software records, and clinical data were extracted, including demographics, aetiologies, pathology, blood transfusions, endoscopic treatment details, re-bleeding, TIPS placement, and mortality. Multivariate analyses identified predictors of mortality, re-bleeding, and TIPS requirement. Cox regression assessed survival outcomes, while logistic regression evaluated re-bleeding within 5 days and TIPS placement.

Results: 89 patients were included (68.5% male, median age 58 years). The most common aetiologies were alcohol (60.7%) and MASLD (20.2%). EGI with histoacryl glue was administered in 83 patients (93%). Survival was lower in Child-Pugh C patients compared to Child-Pugh A patients (HR 3.436, p=0.004). During follow-up, 27 patients (30.3%) experienced a second GVB event. Early re-bleeding within 5 days occurred in 13 patients (14.6%), with 4 not receiving EGI initially. Re-bleeding within 5 days increased with the volume of blood transfused prior to endoscopy (OR 1.273, p=0.015). Five patients required TIPS after initial EGI control—two within 30 days and three over a year later, with only one for repeat variceal bleeding. No predictive variables for TIPS placement were identified. Two patients had serious adverse events related to EGI, including lung and brain embolization.

Conclusion: Overall survival was poorer in Child-Pugh C patients, with higher early re-bleeding rates in those not receiving initial EGI and those requiring larger blood transfusions during resuscitation. TIPS was rarely needed for re-bleeding after EGI. This study underscores the efficacy of EGI in treating acute GVB and highlights the need for further research on optimized treatment protocols for high-risk patients.

559

The utility of protocolled thiopurine metabolite testing in patients with autoimmune hepatitis

Joshua Abasszade¹, Atul Shrestha¹, Ruyi Tan¹, Tobie Abrahams² and Marcus Robertson^1,3

¹Monash Health, Clayton, Australia; ²Alfred Health, Melbourne, Australia; ³Peninsula Health, Frankston, Australia

Background and Aim: Autoimmune hepatitis (AIH) is an immune-mediated inflammatory hepatopathy characterised by hypergammaglobulinemia, specific autoantibodies and interface hepatitis which carries a significant risk of cirrhosis in the absence of timely and effective therapy. Initial treatment of AIH traditionally comprises glucocorticoids and a thiopurine (TP) (azathioprine (AZA) or 6-mercaptopurine (6-MP)) with a view to maintaining steroid-free remission on TP monotherapy. Although well established in the inflammatory bowel disease population, the role of routine TP metabolite (TM) testing in AIH remains uncertain. We aimed to evaluate the utility of routine TM testing in TP dose-optimisation and disease remission.

Methods: We conducted a prospective observational study of adult patients with newly diagnosed AIH who were commenced on a TP as the first steroid-sparing agent at a metropolitan health network between 2014 and 2023. The International Autoimmune Hepatitis Group simplified diagnostic criteria was used to standardise diagnosis of AIH. Baseline demographic, biochemical, serologic and histologic data were recorded along with TP dosing regimens and TM levels. The primary outcomes were: i) biochemical remission (defined as a normal alanine transaminase (ALT) level <33 U/L within 12-months of diagnosis) and, ii) the frequency of TP dose adjustment following TM testing. The correlation between TM testing and the primary outcomes were assessed using a two-tailed T-test and adjusting for Gaussian distribution using Wilcoch’s adjustment. Secondary outcomes included rates of AIH flares (defined as ALT >66 U/L or an increase/reintroduction of steroids in response to a clinical change with an ALT 33-66 U/L), identification of TP non-compliance and shunting requiring addition of allopurinol.

Results: 34 patients were included with a mean follow up time of 34.1 ± 29.4 months. The mean age at diagnosis was 46 ± 17 years, 65.0% were female and 64.7% were Caucasian. Positive anti-smooth muscle antibody and anti-nuclear antibody serology were noted in 15 (44.0%, median titre 1:160 (IQR 1:80 – 1:1140)) and 29 (85.3%, median titre 1:1280 (IQR 1:280 – 1:1280)) patients respectively. Liver biopsy was performed in all patients, with 20 (58.8%) and 5 (14.7%) having definite and probable histologic AIH features respectively; 5 (14.7%) patients were cirrhotic at diagnosis. At the time of diagnosis, the median ALT was 1114 U/L (IQR 657-1249 U/L). Azathioprine was commenced in 91% patients with a median dose of 100 mg daily (IQR 50-112.5 mg) at 12-months; the remaining 9% patients were commenced on 6-MP. Biochemical remission was achieved in 12 (34.3%) and 18 (52.9%) patients at 6- and 12-months respectively. At 12-months, the mean 6-TGN level was 320.4 ± 217.1 pmol/8x10⁸ RBC and the mean 6-MMP was 1295.5 ± 3526.6 pmol/8x10⁸ RBC, with no significant difference in metabolite levels identified between patients who achieved biochemical remission and those that did not. No patient ceased a TP due to side-effects during the study period. Amongst patients who achieved biochemical remission, an AIH flare was documented in 2 (11.1%) patients in the subsequent 12-months. During the study period, 157 TM tests were performed, with a mean number of 4.6 ± 2.4 TM tests per patient. There was a strong correlation between the number of TM measurements performed and biochemical remission (t = 9.476, p < 0.001, 95% CI 4.73-10.77). In addition, 40.1% of TM measurements directly resulted in a TP dose adjustment and non-compliance with TP therapy was identified following 19.1% of TM measurements. TM testing identified shunting in 1 patient necessitating TP dose reduction and addition of allopurinol. Overall, TM testing was strongly correlated with TP dose changes (t = 9.205, p < 0.0001, 95% CI 3.14-12.92).

Conclusion: In patients with AIH treated with a TP, protocolled TM measurement resulted in TP dose optimisation in 40.1% cases and accurately identified both medication non-compliance and metabolite shunting. In addition, there was an association between frequency of TM testing and achievement of biochemical remission.

564

Acute on chronic liver failure in Australia: A non-transplant centre experience

Leo Wan^1,3, Ronan O'Connor¹, Annie Zhou¹, Jennifer Zhang¹, Stephen Bloom^1,2, Alex Hodge^1,2 and Rohit Sawhney¹

¹Eastern Health; ²Monash University; ³Alfred Health

Background and Aim: Acute on chronic liver failure (ACLF) is a clinical syndrome distinct from acute decompensation (AD) of cirrhosis characterised by systemic inflammation, organ failures and increased mortality. There is limited availability in Australian data on ACLF outside of transplant centres. The aim of this study was to describe the prevalence, characteristics and outcomes of ACLF in a cohort of hospitalised patients at a non-transplant Australian tertiary centre.

Methods: A retrospective review was performed of all liver related admissions at a non-transplant tertiary health network in Melbourne between 2018 and 2021. All index admissions of adult patients presenting with acute decompensation on a background of cirrhosis were included. Excluded admissions were those admitted electively, those without acute decompensation, and those with acute decompensation without cirrhosis. Included patients were grouped into either ACLF, as defined by the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium criteria, or AD without ACLF. The patient characteristics, clinical course, and patient survival were analysed.

Results: A total of 245 patients had 452 admissions with acute decompensation. Of their index admissions, 70 admissions (28.6%) met the criteria for ACLF. Both the ACLF and AD groups were predominantly male (p=0.686) with a median age at admission of 56 years (p=0.393). The most common cirrhosis aetiology was alcohol (80.4%). The most common decompensating event was gastrointestinal bleeding in the ACLF group (30.0%) compared to abdominal ascites (48.0%) in the AD group. Median admission model for end-stage liver disease (MELD) scores were higher in ACLF patients compared with AD (25 vs 18, P < 0.001). The most common organ failure amongst the ACLF group was coagulation (45.7%) followed by liver (34.2%) and kidney (31.4%). Of the patients with ACLF, 52 (74.3%) patients met the EASL-CLIF criteria on admission, with a further 18 (25.7%) patients developing ACLF during their admission. 90-day mortality was significantly higher in the ACLF group (44.3% vs 10.8%, p <0.0001). Admission albumin (p=0.018) and white cell count (p=0.039) were the only two predictors of overall mortality.

Conclusion: ACLF was present in over a quarter of patients hospitalised with AD in this cohort and is associated with poor survival. The rate of ACLF in hospitalised patients was similar to previous studies in Europe and Australia with comparable survival rates. Further investigation in and comparison of different cohorts and settings will be important to identify prognostic factors and inform management strategies.

565

Secondary haemophagocytic lymphohistiocytosis triggered by influenza A leading to fulminant liver failure

Chong-Rue Ho¹, William Jiaen Wang^1,2, Withma Muthukumara¹ and Paul Clark^1,3

¹Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia; ²School of Medicine, Western Sydney University, Sydney, Australia; ³Department of Gastroenterology and Hepatology, Mater Hospital Brisbane, Brisbane, Australia

Introduction: Haemophagocytic lymphohistocytosis (HLH) is a rare potentially life-threatening disorder, characterised by the dysregulation of the innate and adaptive immune system. Acute liver injury can occur in the setting of this hyper-inflammatory condition, requiring prompt treatment, which is often delayed due to the diagnostic dilemma it poses. This case report discusses a 39 year old male who had acute liver failure (ALF) due to HLH likely secondary to Influenza A infection.

Case report: A 39 year old male was transferred from a regional hospital to our quaternary centre with acute onset fever, chills, lumbar/hip pain, with dark brown urine and markedly raised transaminases. It was noted his children had PCR confirmed Influenza A one month earlier, after which he had suffered non-specific viral prodrome, with later serological testing consistent with a recent Influenza A infection. On day 3 of his presentation, the patient proceeded to develop encephalopathy and synthetic liver failure with an elevated INR (5.1), elevated bilirubin (379 umol/L) and low albumin (26 g/L). His results demonstrated marked hyperferritinaemia (55,400 ug/L), high triglycerides (3.1 mmol/L), low fibrinogen (1.0 g/L), and trilineage cytopaenia. Liver biopsy demonstrated acute hepatic injury and marked haemophagocytosis. He was worked up for liver transplantation and concurrently commenced on 100mg of IV methylprednisolone. Immunology, hematology and infectious disease consultations were sought. Serum soluble CD25 receptor level, later returned elevated (23,309 pg/ml), confirming criteria-based HLH diagnosis provisionally postulated to be triggered by a delayed reaction to Influenza A. The patient began improving following 2 doses of IV steroids, transitioned to oral steroids and was eventually discharged from hospital with a steroid weaning plan. Approaching twelve months after his discharge, he has had no recurrence of HLH and has been steroid-free for 6 months. This is despite him also contracting COVID-19 and Influenza B during this time (though notably he was still on his steroid weaning plan during these infections).

Conclusion: HLH describes a hyperinflammatory syndrome of immune dysregulation, in particular natural killer cells. While most physicians are familiar with a haematologically driven HLH (often requiring therapy such as stem cell transplant), this case differs from that pattern. The prominent hepatic features, suggest HLH should be considered in the differential for ALF, particularly when acute infective illnesses are also present. Delay in definitive diagnosis of HLH and infective precipitants is often problematic. Whilst the link between HLH and Influenza A has been established in the past with a smattering of case reports^1-4, those cases do not describe a latency period (after contracting Influenza A) prior to developing HLH. It should also be noted that although HLH can cause elevated liver function tests and hepatomegaly, there is a paucity of articles on it causing fulminant liver failure. In this patient’s case, early definitive assessment and treatment avoided liver transplantation.

References

1. Willekens, C, Cornelius, A, Guerry, MJ, Wacrenier, A, Fourrier, F. Fulminant hemophagocytic lymphohistiocytosis induced by pandemic A (H1N1) influenza: a case report. J Med Case Rep. 2011; 5: 280.

2. Zhang, XY, Ye, XW, Feng, DX, Han, J, Li, D, Zhang, C. Hemophagocytic lymphohistiocytosis induced by severe pandemic influenza A (H1N1) 2009 virus infection: a case report. Case Rep Med. 2011; 2011: 1-3.

3. Bahr, Greenwood T, Holzgraefe, B, Chiang, SCC, Wang, Y, Tesi, B, Bryceson, YT, Henter, JI. Clinical and laboratory signs of haemophagocytic lymphohistiocytosis associated with pandemic influenza A (H1N1) infection in patients needing extracorporeal membrane oxygenation: A retrospective observational study. Eur J Anaesthesiol. 2021; 38(7): 692-701.

4. Dlela, M, Turki, O, Bahloul, M, Kallel, H, Jedidi, I, Bouaziz, M. Haemophagocytic lymphohistiocytosis induced by A/H1N1 influenza. Presse Med. 2019; 48(5): 576-578.

566

Liver stiffness changes in transient elastography/FibroScan® after initial assessment in chronic hepatitis B patients: A retrospective observational cohort study

Jacob Ooi, Olga Sukocheva, Anton Colman and Edmund Tse

Royal Adelaide Hospital, Adelaide, Australia

Background: Transient elastography (TE) is used to assess liver stiffness measurements (LSM) and has been routinely used as a non-invasive tool for the assessment of liver fibrosis in many chronic liver diseases including chronic hepatitis B. There is however limited Australian real-world data assessing the role of on-going TE methods, including FibroScan®, after an initial assessment in chronic hepatitis B patients. Particularly, in monitoring chronic Hepatitis B disease progression and response to anti-viral treatment.

Methods: All patients with chronic Hepatitis B at a single tertiary hospital centre who had at least two FibroScan® (initial and follow up) from May 2010 to Feb 2023 were included in the study. FibroScan® results were cross referenced with available Electronic Medical Records (EMR). Data collected included patient demographics, LSM, CAP (controlled attenuated parameter), IQR to median ratio (<0.30), serum alanine aminotransferase (ALT), hepatitis B serology, viral load and other concurrent medical conditions.

Results: 441 patients were initially identified but 10 were excluded due to missing data. Final data analysis included 431 patients of which 76.1% (n=328) had LSM< 7.5kPa (<F1/2 -mild fibrosis), 10.6% (n=46) had LSM of >7.5kPa<9.5kPa (F2/3- moderate) and 13.2% (n=57) had LSM>9.5kPa (F3/F4 -significant fibrosis/cirrhosis). The interval mean duration between initial FibroScan® and second FibroScan® was 37.7 months. 245 patients had either improvement or unchanged LSM and 177 had deterioration of LSM between initial and follow up FibroScan®. Of the 245 patients with improved LSM, 87.8% (n=36) of patients with moderate fibrosis (F2/F3) demonstrated improvement of LSM corresponding to one fibrosis stage improvement. 59.5% (n=25) of patients with significant fibrosis (F3/F4) had two stage fibrosis improvement, 19% (n=8) had one stage improvement and 16.6% (n=7) had improvement to LSM but did not demonstrate fibrosis stage improvement. Of the 177 patients with deterioration in LSM, 9.5% (n=15) of patients with mild fibrosis (F1/F2) demonstrated one stage fibrosis deterioration to F2/F3 and 6.3% (n=10) with two stage fibrosis deterioration to F3/F4. Four patients with moderate fibrosis (F2) deteriorated to F3/F4. Overall, 6.6% (n=29) of patients had LSM deterioration corresponding to fibrosis stage deterioration. Hepatic steatosis is the most common co-factor associated with significant LSM deterioration (n=27). Treatment of immune escape Hepatitis B and weight loss is the most common cause of improvement in LSM (n=61).

Conclusion: Our preliminary data suggests that steatotic liver disease stemming from either Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) or MASLD and increased alcohol intake (MetALD) is vastly the primary driver of LSM changes chronic hepatitis B patients. This is commonly seen in patients in immune control phase. In patient cohort that have been commenced on anti-viral treatment, it is very unlikely that LSM worsens in the absence of other co-factors. Interval repeat TE assessments after anti-viral initiation for progressive liver fibrosis is not required particularly in the absence of transaminitis and presence of other co-factors.

575

A rare case of survival in acute alcohol-related hepatitis with leukemoid reaction

Jennifer Zhang¹, Nicholas Batt¹, James Williams¹, Alex Hodge^1,2 and Rohit Sawhney^1,2

¹Gastroenterology Department, Eastern Health, Melbourne, Australia; ²Eastern Health Clinical School, Monash University, Melbourne, Australia

Introduction: A leukemoid reaction (LR), characterised by an elevated white cell count (WCC) > 50,000 cells/μL as a physiological response to stress or infection is uncommon with alcohol-related hepatitis (AH) but portends a poor prognosis. Mortality rates are as high as 80% across a small number of case studies. Current management is primarily supportive, with limited evidence guiding treatment due to disease rarity. Additionally, while the Maddrey discriminant function (DF) is often used to determine whether patients with AH would benefit from corticosteroids, its utility in patients with concurrent LR is yet to be evaluated. Identifying predictors of survival could inform future management strategies.

Case report: We present the case of a 31 year old man from Myanmar with AH-associated LR, managed conservatively without corticosteroid therapy. He presented with 3 weeks of right upper quadrant abdominal pain, back pain, night sweats, nausea, and vomiting on a background of daily alcohol misuse and known hepatic steatosis. On examination, he was febrile (38°C) and tachycardic (120 bpm), with no signs of decompensated cirrhosis. His viral hepatitis, autoimmune, infective, and metabolic screens were negative. Drug-induced liver injury was ruled out based on his medical history. Imaging showed moderate hepatosplenomegaly and marked hepatic steatosis. His admission DF was 61 and white cell count (WCC) 19,400 cells/mm³. He had prolonged antibiotic therapy for 23 days amidst investigating for persistent fevers of unknown origin, but a total of 16 sets of blood cultures during febrile episodes all returned negative. Differential diagnoses included active tuberculosis (TB), supported by early investigations of a positive QuantiFERON gold test and two primary contacts with active disseminated TB, as well as a possible haematological malignancy due to a leucoerythroblastic blood film and hepatosplenomegaly. Subsequent tests returned negative. On day 21, the patient's inflammatory markers and bilirubinemia peaked: WCC 78,000 cells/mm³, bilirubin 576 μmol/L, MELD score 34 and DF 68. Remarkably, his serological markers improved rapidly after commencing nasogastric feeding on day 31, in addition to oral nutritional supplements prior. This delay in aggressive treatment of his malnutrition was partially due to patient reluctance for enteral feeds. Ultimately, the diagnosis of AH-related LR was concluded, further supported by the active chronic steatohepatitis with features of ethanol effect on liver biopsy. He was discharged after 41 days in hospital with gross normalisation of serology 90 days post-admission.

Conclusion: Our case highlights one of the rare instances of survival in AH-associated LR, as well as the importance of dietary supplementation in addressing malnutrition which is common in this patient subset.

576

Risks for presenting with late-stage hepatocellular carcinoma in Far North Queensland, Townsville region

Melissa Day³, Mohamed Reffai Syed Mohamed¹, Xiao Chang¹, Jonathan Mitchell³, Sophie Willemse³, Seema Shah¹ and Rozemary Karamatic^1,2

¹Townsville University Hospital, Townsville, Australia; ²James Cook University, Townsville, Australia; ³Cairns Base Hospital, Cairns, Australia

Background and Aim: Australia’s incidence of Hepatocellular carcinoma (HCC) has risen 3-fold between 1982 and 2019. This rate depends on geographical region, with very remote regions having the highest incidence. Despite advancements in treatment, mortality from HCC continues to rise and the 5-year survival rate is only 20%. Far North Queensland (FNQ) has unique challenges to patient care in view of the large geographical and remote area serviced. Indigenous Australians are often de-centralized (2 in 3 living outside of metropolitan Queensland) and have a higher incidence of HCC, receive curative therapies less often and have poorer survival. Significant barriers exist for optimal care. The aim of this study was to identify potentially modifiable factors to address this.

Method: A retrospective cohort study of patients diagnosed with HCC at Townsville University Hospital (TUH) between 2014 and 2022 was undertaken. Cancer registry, coding data, multidisciplinary team (MDT) and medical records identified cases. Crude incidence rates were calculated (per 100,000 age-adjusted) and aetiologies identified. Distance from a tertiary centre (defined as > 60km) and ATSI (Aboriginal and Torres Strait Islander) status were independently assessed with regards to the primary and secondary outcomes. Primary outcomes were BCLC (Barcelona clinic liver cancer) stage at diagnosis. Secondary outcomes were time to MDT, time to treatment, participation in HCC screening programs and survival.

Results: 108 incident cases were diagnosed with HCC within the study period, giving an age-adjusted crude incidence 7.5 per 100,000 in 2022. The ATSI rate was 4.65 per 100,000. The most common aetiological factors were alcohol (62%) with viral hepatitis and metabolic associated liver disease making up the remainder (15% and 9% respectively). Later stage at diagnosis (BCLC stage B, C, and/or D) was associated with distance from hospital (52.1% vs 47.9%, p=0.253, OR 1.60 (95% CI 0.71-3.60)) and ATSI patients (70.6% vs 64.8% p=0.646, OR 1.30 (95% CI 0.42-4.2) but did not reach statistical significance. Secondary outcomes did not demonstrate increased risk in either of the independent variables.

580

Outcomes of using software automation tools to efficiently coordinate multidisciplinary team meetings for hepatocellular cancer

Suresh Sharma, Khaliun Batkhurel, Rebecca Johnson, Ebony Jobse, Robert Gibson, Lay Theng Gan and Steven Bollipo

Gastroeneterology Department, John Hunter Hospital, Newcastle, Australia

Background: Most clinical data management applications lack vital clinical recall for Hepatocellular Cancer (HCC) follow-up, leading to inefficient workflows and fragmented team communication. While bespoke solutions are an option, Microsoft 365 (MS365) offers a widely accessible, secure, and versatile platform for data management. MS365 facilitates data coordination and provides tools for automating the synthesis of clinical information prior, during and post multidisciplinary meetings, addressing the inefficiencies in managing patient data of those with HCC and actions required.

Aim: We present our usage of MS365 in our clinical and diagnostic decision making, using available suite of software products to efficiently manage the care discussion of people with a known or suspected HCC in a Multidisciplinary Team (MDT) setting.

Methods: We describe the usage of MS365 applications such as Forms, Teams, Excel, Word, Outlook, and Power Automate, to suspect and know case of HCC in our MDT between October 2020 to April 2024.

Discussion: As visualised, the system encompasses MDT referral, methods for image transfer and pathology input, calculation of relevant scores, self-triaging for discussion urgency, generation, and dissemination of discussion lists, capturing clinical discussion, formulating recommendations, generating formal correspondence, developing action lists for recommended treatment, assigning post-MDT tasks, and coordinating workflow management. This comprehensive approach ensures efficient communication, collaboration, and task management within the HCC MDT framework.

Conclusion: Our systematic approach, facilitated by the comprehensive capabilities of MS365, has enabled the effective management of a large patient volume while significantly reducing instances of redundant tasks. By utilising a familiar, readily accessible, and secure platform, we have streamlined the MDT referral process, ensuring timely patient care within our resource constrained environment.

582

Development of rapidly progressive metabolic associated fatty liver disease after single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S)

Mustafa Mohamedrashed

Peninsula Health, Frankston, Australia

Introduction: Metabolic associated fatty liver disease (MAFLD) is an inflammatory liver disease that can lead to fibrosis and end-stage liver disease. The primary management approach focuses on means to achieve weight loss. Bariatric interventions have shown promising results in improving MAFLD, this is the first reported case of significant MAFLD post SADI-S, suggesting similar hepatic injury mechanism to alcoholic hepatitis.

Case report: A non-alcoholic, non-smoker, and pre-morbidly obese (pre-operative BMI of 65) female in her 40s, presented with 80kg weight loss over 8-months, associated with progressively worsening nausea, vomiting, and abdominal pain after SADI-S. detailed history excluded risk factors for infective hepatitis and toxins induced liver injury. Physical examination showed right upper quadrant abdominal tenderness and massive hepatomegaly with a span of 21 cm. blood test revealed mild macrocytic anaemia with a haemoglobin level of 112 g/L, Normal folate, B12, Lipase, and coagulation screen. Liver function test was deranged in mixed pattern with ALT: 44units/L, AST: 123 units/L, ALP: 270 units/L, GGTP:169 units/L, Bilirubin: 71 μmol/L. Additional blood tests were negative for infective hepatitis and autoimmune screen. Magnetic resonance cholangiopancreatography showed prominent intrahepatic biliary ducts without dilatation of the biliary or pancreatic ducts and massive hepatomegaly measuring 29 cm. Gastroscopy did not show any acute or chronic upper gastrointestinal pathologies. Histological examination showed preserved hepatic architecture with marked macrovesicular steatosis associated with steatohepatitis characterised by the presence of numerous ballooned hepatocytes and scattered Mallory-Denk bodies which are often observed in alcoholic steatohepatitis. However, minimal pericellular fibrosis was observed. Additionally, patchy mild lobular inflammation and moderate mixed acute and chronic portal inflammatory infiltrate, composed of lymphocytes and neutrophils with occasional eosinophils and plasma cells were noted. Aggressive form of MAFLD was diagnosed. Patient showed significant symptomatic improvement concordant with improvement in her LFT with dietary interventions. Primarily by avoiding further excessive weight loss.