{"title":"The impact of first and further decompensation in patients with metabolic-dysfunction associated compensated advanced chronic liver disease","authors":"","doi":"10.1016/j.dld.2024.08.005","DOIUrl":"10.1016/j.dld.2024.08.005","url":null,"abstract":"<div><h3>Background & Aim</h3><p>The first and further decompensation mark the natural history and the risk of mortality in patients with cirrhosis. We assessed the cumulative incidence of first and further (acute and non-acute) decompensation and evaluated their impact on both liver-related death (LR-D) in patients with compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD).</p></div><div><h3>Methods</h3><p>Consecutive patients with clinical (LSM>10 kPa) or biopsy-proven (F3-F4 fibrosis) diagnosis of cACLD due to MASLD were included. First and further decompensation were defined according to Baveno VII criteria. The acute (AD) and non-acute (NAD)[MOU1] [VW(2] presentation of the decompensation was also evaluated. Competing risk analysis and cumulative incidence functions (CIF) [MOU3] were assessed by Fine and Gray. Cause-specific Cox models with baseline and time-dependent variables were applied. Multistate model was built to better assess the clinical course of cACLD due to MASLD.</p></div><div><h3>Results</h3><p>The cumulative incidence of the first decompensation was 3.5% at 5 years, increasing 20-times the risk of LR-D at cause-specific Cox analysis; the cumulative incidence of further decompensation was 44% at 5 years among patients with first decompensation, additionally increasing 1.6-times the risk of LR-D. Ascites, followed by variceal bleeding, were the most common events in both first and further decompensation. The impact of AD and NAD as both first or further event on LR-D was similar[MOU4] . Hepatocellular carcinoma (HCC) further independently increased the risk of LR-D of 3.2-times and 1.6-times, respectively, in the whole cohort of cACLD due to MASLD and in those who experienced first decompensation.</p></div><div><h3>Conclusions</h3><p>The first and further decompensations (AD and NAD) represent tipping points in the clinical course of patients with cACLD due to MASLD, increasing 20-times and additionally 1.6-times the risk of LR-D. HCC is an independent predictor of LR-D in patients with cACLD due to MASLD, resulting in an additional risk of LR-D when associated with both first and further decompensation.</p></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sarcopenia, malnutrition, and pruritus: a cholestasis-related “Cerberus” severely impacting the quality of life in patients with Primary Biliary Cholangitis (PBC). Is the systemic oxidative stress imbalance the driver? A preliminary observation","authors":"","doi":"10.1016/j.dld.2024.08.027","DOIUrl":"10.1016/j.dld.2024.08.027","url":null,"abstract":"<div><h3>Introduction</h3><p>Sarcopenia and malnutrition are a two-faced Janus affecting prognosis in parallel with disease progression status (DPS) in various chronic liver disorders, with an unexplored role in Primary Biliary Cholangitis (PBC). Micronutrient absorption influences systemic oxidative stress imbalance (SOS-I). SOS-I impacts muscle metabolism and itch pathways, representing a leitmotif contradistinguishing PBC. Cholestasis-related malabsorption and pruritus mainly burden PBC quality of life (QoL).</p></div><div><h3>Aim</h3><p>In PBC, to explore the relationship between sarcopenia, malnutrition, SOS (according to DPS, compared with other CLDs-etiologies), and pruritus, estimating the impact on the QoL.</p></div><div><h3>Materials and Methods</h3><p>40 MASLD, 52 HBV, 50 HCV, and 41 ursodeoxycholic-acid/antioxidants-naïve receiving a first serological PBC diagnosis patients were enrolled. Clinical, biochemical, nutritional (food-intake + bioelectric-impedance-analysis), and Liver-Stiffness (LSM) data were collected after a 3-month equally prescribed dietetic-physical exercise regimen. EWGSOP2 criteria diagnosed sarcopenia. The d-ROMs/BAP test evaluated SOS: d-ROMs > 27.20 mgH<sub>2</sub>O<sub>2</sub>/dL+ BAPs < 2000 µmol-iron/L = SOS-I. PBC-40 questionnaire estimated pruritus and QoL (poor > 120).</p></div><div><h3>Results</h3><p>In PBC, sarcopenia was more prevalent even in initial-mild fibrosis (F0-F2) (PBC: 67.90% <strong>vs</strong> MASLD: 30.76%, HBV: 22.60%, HCV: 20.70%, all <em>p</em><0.0001). Appendicular-skeletal-muscle-mass/height<sup>2</sup>(ASM/h<sup>2</sup>) and LSM correlated exclusively in MASLD and HBV/HCV (both <em>p</em><0.0001). PBC patients with severe cholestasis and sarcopenia presented lower micronutrient levels, particularly vitamin D (PBC <strong>vs</strong> MASLD, HBV, HCV all <em>p</em>: 0.001). In PBC, SOS correlated with gamma-glutamyl-transferase (d-ROMs, R:0.748, <em>p</em>:0.002; BAP, R: -0.641, <em>p</em>: 0.004) and alkaline-phosphatase (d-ROMs, R:0.781, <em>p</em>:0.03; BAP, R: -0.702, <em>p</em>:0.01). Limitedly to PBC, SOS correlated with muscle mass quantity (BAP-ASM/h<sup>2</sup>, R: 0.871, d-ROMs-ASM/h<sup>2</sup>, both <em>p</em><0.0001), and pruritus severity (d-ROMs-item3-PBC-40, R:0.835; BAP-item3-PBC-40, R: -0.775, both <em>p</em><0.0001). SOS-I was more prevalent in PBC patients with sarcopenia and severe pruritus (<em>p</em>:0.023). A poor QoL was more represented in PBC individuals simultaneously showing sarcopenia, severe pruritus, and SOS-I (<em>p</em>: 0.001).</p></div><div><h3>Conclusions</h3><p>In PBC, cholestasis promotes sarcopenia, malnutrition, and pruritus, dramatically impacting the QoL via SOS-I.</p></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impaired nutritional status, frailty and inadequate dietary intake: a reality still underdiagnosed in liver cirrhosis patients","authors":"","doi":"10.1016/j.dld.2024.08.006","DOIUrl":"10.1016/j.dld.2024.08.006","url":null,"abstract":"<div><h3>Introduction</h3><p>Malnutrition and frailty are common in liver cirrhosis (LC) patients, increasing morbidity and mortality, especially in advanced stages. Despite their impact on prognosis, they are often overlooked and underdiagnosed.</p></div><div><h3>Aim</h3><p>To provide an overview of the nutritional status, frailty and dietary intake in LC patients, both outpatients and hospitalized, enrolled in a recent cross-sectional study before starting nutritional counselling.</p></div><div><h3>Materials and Methods</h3><p>In this prospective observational study, all consecutive LC patients attending the portal hypertension clinic and/or admitted to the gastroenterology unit at Policlinico Umberto I University Hospital from May 2023-January 2024 underwent nutritional screening. Screening included SARC-F questionnaire for sarcopenia, anthropometric measurements, liver frailty index (LFI) assessment, 24-hour diet recall, and food frequency questionnaire. Data were analyzed using Student's t-test and chi-square test by Jamovi software V2.3.28.</p></div><div><h3>Results</h3><p>Altogether 126 patients [72% male; age 63.7±10.7years; etiology:Alcohol-53%, MASLD-19%, Viral-20%, Others-8%; MELD- 11.8±4.4; MELD Na- 13.6±5.5; 50%Child A] were enrolled. According to SARC-F questionnaire, 36% were sarcopenic (score ≥4) and > 90% were frail or pre-frail (mean LFI 4.6±0.9). Although 65% patients consumed at least one protein source daily, 85% failed to achieve recommended daily protein intake, and 78% had lower than recommended caloric intake. Of the cohort, 68.3% were outpatient and 31.7% were hospitalized patients, with comparable age and gender distribution. Hospitalized patients had lower BMI(kg/m<sup>2</sup>) [24.7±4.1 vs 27.8±6.9;p=0.01], higher frailty scores [LFI 5.1±1.1 vs 4.3±0.7;p≤0.001], lower TSF(mm) [12.4±6.8 vs 16.2±8.1;p=0.04], and lower MUAC(cm) [29.6±5.1 vs 32.2±5.6;p=0.02] than outpatients. Further, none of the hospitalized patients met adequate protein intake, contrasting with 22% of outpatients (p=0.01).</p></div><div><h3>Conclusion</h3><p>There is still a high need for timely assessment of nutritional status, frailty and dietary intake in all chronic liver disease patients. This is true for both more severe hospitalized patients and outpatients and represents the premise for planning further lifestyle interventions to optimize patient outcomes.</p></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characteristics and Outcomes of Hepatocellular Carcinoma (HCC) in Patients with Autoimmune Hepatitis (AIH): Insights from the Italian Liver Cancer (ITA.LI.CA) Database","authors":"","doi":"10.1016/j.dld.2024.08.022","DOIUrl":"10.1016/j.dld.2024.08.022","url":null,"abstract":"<div><h3>Introduction</h3><p>The incidence of HCC in patients with autoimmune hepatitis AIH patients is low (0.09% per year), with higher risk in those with additional risk factors.</p></div><div><h3>Aim</h3><p>To report characteristics and outcomes of patients with AIH and HCC.</p></div><div><h3>Materials and Methods</h3><p>We analyzed data from the ITA.LI.CA database (2009-2022) including 8,038 HCC and identified 18 patients (0.2%) with AIH and HCC. We evaluated liver disease-related characteristics, modality of HCC diagnosis, tumor stage, treatment, recurrence, overall survival (OS), and causes of death.</p></div><div><h3>Results</h3><p>Median age was 67.2 years, and male patients represented 50.0% of cases. Most patients had cirrhosis (90%). Two patients (11.1%) had Primary Biliary Cholangitis overlap, three (16.7%) concomitant alcohol abuse, while 4 (22.2%) and 3 (16.7%) were overweight and obese, respectively. Median MELD score was 11 (IQR 9-13). HCC diagnosis occurred primary during surveillance (55.6%). Most patients had single tumour (77.8%), median HCC diameter was 2.8cm (1.5–3.2), three patients (16.7%) had extra-hepatic spread or macro-vascular invasion, and 72.2% were Milan-in. Treatment with curative intent was performed in 11 patients (33.3% ablation, 22.2% resection, 5.5% transplantation). Trans-arterial chemoembolization was carried out in 6 patients (33.3%), and one patient (5.5%) was managed with best supportive care. Objective response was observed in 66.7% of patients, and early recurrence occurred in 2 patients (11.8%). Median OS was 41.7 months, and main causes of death were end-stage liver disease (57.1%) and HCC progression (42.9%). OS was longer in patients under surveillance than in those diagnosed incidentally or due to symptoms (27.3 <em>vs.</em> 62.8 months, p=0.049).</p></div><div><h3>Conclusions</h3><p>HCC in AIH is a rare event, occurring prevalently in older, male patients with cirrhosis, and with frequent concurrent factors for HCC occurrence. A high surveillance rate is associated with favorable staging at diagnosis, and with access to potentially curative treatments, thus resulting in improved survival.</p></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Depression and anxiety among patients with hepatocellular carcinoma evaluated for liver transplantation","authors":"","doi":"10.1016/j.dld.2024.08.032","DOIUrl":"10.1016/j.dld.2024.08.032","url":null,"abstract":"<div><h3>Introduction</h3><p>Hepatocellular carcinoma (HCC) mostly develops in a cirrhotic liver and represents a serious public health problem. Liver transplantation (LT) is a therapeutic option for HCC that offers to patients a long-term survival.</p></div><div><h3>Aim</h3><p>The aim is to investigate depression and anxiety in HCC patients evaluated for LT.</p></div><div><h3>Materials and Methods</h3><p>Retrospective study (N=179) at liver disease clinic on patients with a diagnosis of cirrhosis evaluated for LT. Inclusion criteria: completion of the psychological evaluation for eligibility to transplantation. The sample was divided in two groups: HCC (89/179; 49.7%) and no-HCC. Patients underwent a psychological evaluation with clinical interviews and psychological assessment with self-report questionnaires for depression (BDI-II), anxiety (BAI) and general psychological problems (SCL-90). Descriptive analyses and linear regression analyses were performed.</p></div><div><h3>Results</h3><p>Among the 179 patients, 84.9% were men, the mean age was 58 years. HCC group has lower depression (<em>p</em>< .01), anxiety (<em>p</em>< .05), SCL-Somatization, SCL-Depression, and SCL-Anxiety (<em>p</em>< .05) than no-HCC group. They also have a lower severty of liver disfunction (MELDNa) (<em>p</em>< .001). Univariate linear regression analysis highlighted a correlation between depression (BDI-II) and respectively: age, gender, HCC, MELDNa class and psychopathological anamnesis. Multivariate linear regression analysis [covariate: male gender OR -3.6 (95% CI -7.11– -0.21); psychopathological anamnesis OR 6.3 (95% CI 3.87 – 8.77), HCC OR -4.3 (95% CI -6.88 – -1.80); <em>p</em>< 0.05] highlighted that depression is positively associated with psychopathological history and inversely with HCC and male gender.</p></div><div><h3>Conclusions</h3><p>Counterintuitively, patients with HCC show less depression/anxiety than patients without HCC, probably because of multiple loco-regional or systemic oncologic therapies. HCC and male gender have a significant effect on depression. HCC patients may not perceive the severity of their liver disease and lack of insights on it, therefore it could be important to enhance their compliance to the transplant programs.</p></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Autoimmune liver diseases and autoimmune atrophic gastritis: an overlooked association?","authors":"","doi":"10.1016/j.dld.2024.08.017","DOIUrl":"10.1016/j.dld.2024.08.017","url":null,"abstract":"<div><h3>Introduction</h3><p>Autoimmune atrophic gastritis (AAG) is a chronic condition characterized by the presence of atrophy in the oxyntic mucosa and a spared antrum, frequently with presence of anti-parietal cells antibodies (APCA). The prevalence of AAG has been estimated at between 0.3% and 2.7% in the general population. AAG can be associated with other autoimmune disorders such as type I diabetes, thyroid disease, vitiligo and alopecia. In literature there are only a few case reports showing the association between AAG and autoimmune liver diseases (primary biliary cholangitis=PBC, primary sclerosant cholangitis=PSC, and autoimmune hepatitis=AIE)</p></div><div><h3>Aim</h3><p>The aim of this study was to evaluate the prevalence of AAG in patients affected by autoimmune liver diseases (PBC, PSC and AIE).</p></div><div><h3>Methods</h3><p>We conducted a prospective study in a cohort of 46 patients with a diagnosis of either PBC (26/46, 56.5%), PSC (1/46, 2.1%), AIE (11/46, 23.9%), or an overlap PBC/AIE (8/46, 17.3%) who underwent, according to our prescription, gastroscopy (EGDS) for different reasons (dyspepsia, anemia, diarrhea, reflux symptoms or search for esophageal varices). Biopsies during EGDS were taken following the updated Sydney System protocol.</p></div><div><h3>Results</h3><p>45/46 (97.8%) patients were female, while only 1 patient (2.1%) was male. Nine (19.5%) out of 46 patients were diagnosed with AAG, with histological evidence of atrophy in the oxyntic mucosa only. Moreover, 7 of these patients had positive APCA, while in the other 2 patients APCA were not tested. Six of these 9 patients were affected by PBC, 2 had AIE and 1 had an overlap syndrome (PBC/AIE). In addition, 23/46 (50%) patients had other autoimmune disorders.</p></div><div><h3>Conclusion</h3><p>Our study showed a strong association between AAG and autoimmune liver diseases raising the question of the need of gastroscopy with adequate biopsy sampling and/or serological assay of APCA in patients diagnosed with liver autoimmune diseases to screen for AAG.</p></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cardiometabolic risk factors and clinical course of liver cirrhosis","authors":"","doi":"10.1016/j.dld.2024.08.018","DOIUrl":"10.1016/j.dld.2024.08.018","url":null,"abstract":"<div><h3>Introduction</h3><p>The global prevalence of Metabolic Dysfunction-Associated Liver Disease (MASLD) is dramatically increasing with the diffusion of cardiometabolic risk factors. The aim of the present study was to assess the natural course of liver cirrhosis, in terms of decompensation, development of hepatocellular carcinoma and mortality, in relation to the presence of cardiometabolic risk factors (type 2 diabetes mellitus, obesity, arterial hypertension, low HDL levels, hypertriglyceridemia). Patients: 667 patients with liver cirrhosis (50 with MASLD aetiology, 167 with non-MASLD aetiology, and 450 with a non-MASLD etiological factor plus the presence of at least one cardiometabolic risk factor) followed at the University and General Hospital of Padua, Italy, from 1998 to 2022, were included.</p></div><div><h3>Results</h3><p>No difference in the occurrence of cirrhosis decompensating events and development of hepatocellular carcinoma was observed, whereas patients in the MASLD or mixed group had 4-3-fold higher all-cause mortality and significantly lower 3-years survival compared to patients with non-MASLD cirrhosis, despite a better liver function at enrolment. Hypertriglyceridemia and low HDL levels were the less prevalent cardiometabolic factors, but those associated with the highest risk of cirrhosis decompensation. Hypertriglyceridemia was also associated with an increased risk of mortality. Arterial hypertension was associated with a reduced risk of cirrhosis decompensation, but a higher risk of mortality.</p></div><div><h3>Conclusion</h3><p>Compared to patients with non-MASLD cirrhosis, those with cardiometabolic risk factors had similar rates of liver cirrhosis decompensation but higher overall mortality. Hypertriglyceridemia was associated with a high risk of both liver decompensation and death.</p></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An innovative annotation tool for selecting Regions of Interest (ROI) in contrast-enhanced imaging ultrasonography (CEUS) of Hepatocellular carcinoma (HCC)","authors":"","doi":"10.1016/j.dld.2024.08.028","DOIUrl":"10.1016/j.dld.2024.08.028","url":null,"abstract":"<div><h3>Introduction</h3><p>CEUS is a safe and cost-effective imaging technique which allows a real-time evaluation of focal liver lesions (FLL). It has become a fundamental tool in HCC surveillance and diagnosis. Nevertheless, some concerns have risen in the past on its diagnostic accuracy, in particular in its ability to discriminate between HCC and small (<3 cm) Intraepatic cholangio-Carcinoma (ICC). Recent advances in AI-driven tools for medical imaging have demonstrated the potential of greatly improving accuracy. In ultrasonography, they have been proposed to perform diagnosis from CEUS images alone or in combination with Bi-modal ones: the former can provide information about the contrast pattern; the latter enhances structural characteristics.Two challenges arise in the use of machine learning in the analysis of liver ultrasound images. First, the lack of large public datasets, which makes it difficult to train deep learning models, capable of extracting powerful features, optimized for the task: Radiomics, represents an effective technique for extracting powerful quantitative features without the need of a training dataset. Second, the need for complete and standardized annotations, crucial for effective model training.</p></div><div><h3>Aims</h3><p>To build an annotation software capable of selecting ROIs in CEUS imaging and of extracting Radiomics features from both CEUS and B-Mode views, with the intention to build an automated detection software protocol for FLL diagnosis.</p></div><div><h3>Methods</h3><p>A stand-alone tool for annotating CEUS exams and extracting Radiomics features from the annotated ROIs is proposed. It inputs a CEUS exam stored in a WMV or a DICOM file, which includes both B-mode and CEUS views in split screen manner. It allows the radiologist to select the more suitable frame to be annotated within the exam. Two automatisms are introduced in the annotation procedure: first, the tool is capable of replicating in real-time the annotation performed by the annotator on one view, onto the other one. In addition, it is capable of automatically interpolating contour points of the lesion, in case the annotator will not perform a complete annotation. Once annotation is performed, both annotated CEUS and B-Mode views are prepared for labeling and feature extraction. Labeling concerns both the selection of the phase the frame belongs to, i.e., arterial, portal or late, and the type of annotated lesion. Feature extraction instead is performed through Radiomics: to this aim, the annotated views are automatically saved into two distinct NifTI files, from which histogram-based, shape-based and texture based Radiomics features are automatically extracted through PyRadiomics and saved into a specific folder for that exam. A total number of 102 features are automatically extracted and saved from each view.</p></div><div><h3>Results</h3><p>The proposed tool has been positively evaluated by radiologists from the University of Sa","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of causes and patterns of albumin structural damages in commercial formulations","authors":"","doi":"10.1016/j.dld.2024.08.011","DOIUrl":"10.1016/j.dld.2024.08.011","url":null,"abstract":"<div><h3>Introduction</h3><p>The administration of human albumin (HA) is widely used in patients with decompensated cirrhosis to treat or prevent complications of the disease. HA is given to these patients because of its ability to effectively counteract hypovolemia by acting as a plasma expander. However, several lines of evidence suggest that the non-oncotic properties of the molecule may mediate the beneficial effects. Nevertheless, the HA molecules contained in standard commercial HA solution exhibit a number of oxidative and non-oxidative modifications that may dampen the therapeutic potential of commercial HA formulations. Unfortunately, definitive data on the cause and pattern of HA structural damage in commercial solutions are still lacking, so this study identifies critical steps in the manufacturing process as well as in the shelf life for the onset of structural damage in current commercial solutions.</p></div><div><h3>Methods</h3><p>Albumin molecular structure was investigated by using high-performance liquid chromatography/electrospray ionization/mass spectrometry throughout the manufacturing process and at different lengths of shelf-life in standard commercial vials.</p></div><div><h3>Results</h3><p>The LC-MS analysis of samples collected at different steps of the fractionation process indicate that this procedure does not significantly affect albumin quality as the relative amount of reversibly and irreversibly oxidized albumin forms as well as the amount of albumin in its native form at the beginning of the post-production storage period resembles that of healthy donors. Contrary to the manufacturing process, shelf-life at room temperature was found to significantly impair the structural integrity of albumin already after 1 year, with a significant increase of the oxidized (HNA1: +10%; HNA2: 20%) and truncated (N-terminal: +29%) isoforms and a concomitant decrease of the reduced (HMA: -30%) and native (-40%) isoforms. Such results were confirmed by a prospective study in which several strategies to prevent the loss of native albumin in commercial formulation were also tested.</p></div><div><h3>Conclusions</h3><p>This study unveiled that structural damages to the albumin molecule found in commercial formulation do not result from the manufacturing process, but they accumulate during shelf-life at room temperature.</p></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hepatitis delta virus (hdv) replication through hbv integrants in hcc recurrence after liver transplantation","authors":"","doi":"10.1016/j.dld.2024.08.030","DOIUrl":"10.1016/j.dld.2024.08.030","url":null,"abstract":"<div><p>A PWID man, HCV/HBV-HDV/HIV-infected, underwent liver transplantation (LT) for HCC in 2012 at the age of 52 years. HCC tissue showed high HDV-RNA (88,400 copies/cell), low total HBV-DNA (0.00001 c/c), and HBVcccDNA0.00008 c/c), without detectable HBV-RNA. High-throughput HBV integration sequencing (HBIS) identified 657 HBV integration sites.HBV integrants were predominantly represented by HBx gene sequences. After LT, Tacrolimus, Bictegravir/Emtricitabine/TAF, and anti-HBs immunoglobulin were administered, yielding HBsAg, HDV-RNA, and HCV-RNA negativity.</p><p>In 2018, HBsAg reversion was observed with undetectable HBV-DNA and HDV-RNA >19,000 c/ml.</p><p>In 2019, HDV-related hepatitis occurred. Intrahepatic HBcAg, HBsAgHBV DNA, HBVcccDNA, and HBV-RNA were undetectable. HDV RNA concentrations were very high in the liver (3,920,000 c/c) but low in the serum (214 IU/mL). CT scan (CTs) suspected an isolated HCC recurrence in the left adrenal gland, confirmed by adrenalectomy. Real-time PCR in the tumor from the adrenal gland revealed high levels of HDV RNA (5.5 c/c) but low levels of HBV DNA (0.00009 c/c) and HBVcccDNA (0.00001 c/c). HBV RNA was undetectable. HBIS identified 3497 HBV integrations, most of which included HBs gene sequences. After adrenalectomy, HBsAg and HDV-RNA became undetectable. Anti-HBs immunoglobulin was continued with Everolimus.</p><p>In 2021, CTs showed two HCC nodules in the liver and one in the right adrenal gland. TACE was performed, and TKI therapy was started.</p><p>In 2023, new HDV hepatitis occurred, with HDV-RNA>3,631,360 UI/ml and HBV-DNA <10UI/ml. For the progression of HCC, RFA on the right adrenal gland was performed, and Bulevirtide was started. After 3 months, HDV-RNA was 48,638 c/ml, and transaminases were normal.</p><p>This case demonstrates HDV replication in extrahepatic HCC recurrence, despite low levels of HBVcccDNA. The decreased HDV RNA levels after RFA and BLV therapy suggest that HCC metastases may serve as HBsAg production sites following HBV integration.</p></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}