Digestive and Liver Disease最新文献

{"title":"Prevalence and impact of Clinically Significant Portal Hypertension (CSPH) in patients with Hepatocellular Carcinoma (HCC): a multicenter cohort study on the ITA.LI.CA database","authors":"R. Chen ,&nbsp;M. Dibetto Rimondini ,&nbsp;E.G. Giannini ,&nbsp;V. Santi ,&nbsp;F. Pelizzaro ,&nbsp;A. Sangiovanni ,&nbsp;G. Cabibbo ,&nbsp;F. Marra ,&nbsp;F.G. Foschi ,&nbsp;G. Svegliati-Baroni ,&nbsp;F.R. Ponziani ,&nbsp;G. Missale ,&nbsp;F. Morisco ,&nbsp;R. Sacco ,&nbsp;G. Ghittoni ,&nbsp;C. Saitta ,&nbsp;G. Vidili ,&nbsp;F. Azzaroli ,&nbsp;M.R. Brunetto ,&nbsp;S. Boninsegna ,&nbsp;F. Piscaglia","doi":"10.1016/j.dld.2025.01.097","DOIUrl":"10.1016/j.dld.2025.01.097","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Clinically significant portal hypertension (CSPH) is a known independent predictor of hepatocellular carcinoma (HCC) development and prognosis, influencing patient access to oncological treatments. This study aims to evaluate the prevalence of CSPH and its impact across different HCC stages according to the Barcelona Clinic Liver Cancer (BCLC) staging system.</div></div><div><h3>Method</h3><div>A retrospective analysis was conducted on HCC patients registered in the Italian Liver Cancer (ITA.LI.CA) database between January 1987 and December 2022. Patients in BCLC stage D or stage C without extrahepatic metastasis or macrovascular invasion and those with Child-Pugh score &gt; B7, were excluded. The presence of CSPH was assessed through esophageal/gastric varices, tense ascites, or liver stiffness &gt; 25 kPa.</div></div><div><h3>Results</h3><div>Of 10,907 total patients, 7,069 were included, with 2,652 diagnosed with CSPH. CSPH prevalence was highest in alcoholic etiology and BCLC stage C (44.7%), followed by stages A (39.1%), B (33.9%), and 0 (19.6%). CSPH correlated with reduced survival overall, particularly in stages A, B, and C in univariate analysis, but not in stage 0. Multivariate analysis confirmed this association for stages A and B, but not for stage C. Only 9.7% of CSPH patients were on non-selective beta-blockers (NSBB), and although NSBB use improved survival in univariate analysis, it did not in multivariate analysis.</div></div><div><h3>Conclusion</h3><div>This study found that CSPH significantly impacts survival in early and intermediate stages of HCC, but not in very early or advanced stages, likely due to milder liver disease in very early stages (or more frequent access to liver transplantation) or a dominant oncological burden in advanced stages. CSPH is common in advanced HCC patients, who often require anti-angiogenic therapies that necessitate careful management due to the presence of CSPH. Further analysis is underway, including a subgroup analysis of BCLC-C patients based on venous invasion.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Pages S52-S53"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578298","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":"Contrast-enhanced intraoperative ultrasound improved hepatic recurrence-free survival in initially unresectable colorectal cancer liver metastases","authors":"HuiFang Li ,&nbsp;Ming Shi ,&nbsp;Xingzhang Long ,&nbsp;Pinzhu Huang ,&nbsp;Chuan Peng ,&nbsp;Wei He ,&nbsp;Yuhong Li ,&nbsp;Binkui Li ,&nbsp;Yunfei Yuan ,&nbsp;JiLiang Qiu ,&nbsp;Ruhai Zou","doi":"10.1016/j.dld.2024.09.009","DOIUrl":"10.1016/j.dld.2024.09.009","url":null,"abstract":"<div><h3>Background</h3><div>We aimed to evaluate the role of Contrast-enhanced intraoperative ultrasound (CE-IOUS) with perfluorobutane microbubbles (Sonazoid) in improving the prognosis of patients with unresectable colorectal cancer liver metastases (CRLM).</div></div><div><h3>Methods</h3><div>A total of 130 Patients with unresectable CRLM who underwent curative hepatic resection at our institute were retrospectively analyzed. Of these 130 enrolled patients, 67 underwent intraoperative ultrasound alone (IOUS group); 63 underwent additional CE-IOUS and IOUS (CE-IOUS group). Normalized inverse probability treatment weighting (IPTW) was employed to balance baseline characteristics between groups. Hepatic recurrence-free survival (HRFS) and overall survival (OS) were compared.</div></div><div><h3>Results</h3><div>The treatment strategy was altered in 25 patients (25/63, 39.9%) due to the additional use of CE-IOUS. After applying IPTW, the CE-IOUS group exhibited a significantly lower rate of hepatic recurrence (hazard ratio [HR], 0.55; 95% confidence interval [CI] 0.32–0.95; <em>P</em> = 0.032). Subgroup analysis showed that CE-IOUS provided a significant benefit over IOUS in patients with bilobar liver metastases (<em>P</em> = 0.007), or with a number of live tumors &lt; 3 (<em>P</em> = 0.021), or without DLM (<em>P</em> = 0.018), or with extrahepatic metastasis (<em>P</em> = 0.034), or with a minimum of 6 cycles of systemic therapy (<em>P</em> = 0.03).</div></div><div><h3>Conclusions</h3><div>CE-IOUS is necessary for unresectable CRLM after preoperative chemotherapy, as it enhances detection accuracy and improves the prognosis of unresectable CRLM patients.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 2","pages":"Pages 467-476"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343580","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":"Current management of hepatobiliary malignancies between centers with or without a liver transplant program: A multi-society national survey","authors":"Matteo Serenari ,&nbsp;Roberta Angelico ,&nbsp;Quirino Lai ,&nbsp;Damiano Patrono ,&nbsp;Irene Scalera ,&nbsp;Emanuele Kauffmann ,&nbsp;Duilio Pagano ,&nbsp;Riccardo De Carlis ,&nbsp;Enrico Gringeri ,&nbsp;Alessandro Vitale","doi":"10.1016/j.dld.2024.09.007","DOIUrl":"10.1016/j.dld.2024.09.007","url":null,"abstract":"<div><h3>Background</h3><div>Availability of liver transplantation (LT) as a treatment for hepatocellular carcinoma (HCC) and other liver malignancies may determine heterogeneity of therapeutic strategies across different centers.</div></div><div><h3>Aims</h3><div>To investigate the practice between hepato-biliary centers without (HB centers) and with a LT program (LT centers), we launched a 38-item web-based national survey, with directors of centers as a target.</div></div><div><h3>Methods</h3><div>The survey, including 4 clinical vignettes, collected data on their approach to HCC and transplant oncology.</div></div><div><h3>Results</h3><div>After duplicates removal, 75 respondents were considered. Respondents from LT centers (n = 22, 29.3 %) were more in favor of LT in the case of HCC outside Milan criteria (90.9 % vs. 67.9 %, p = 0.037), recurrent HCC (95.5 % vs. 50.9 %, p = 0.002) and other malignancies such as cholangiocarcinoma or neuroendocrine tumors. No significant difference was observed concerning the proportion of centers favorable to LT for unresectable colorectal liver metastases (100 % vs. 88.7 %, p = 0.100).</div></div><div><h3>Conclusion</h3><div>This national survey showed how management of HCC and awareness of transplant oncology may differ between HB and LT centers. Effective networking between HB and LT centers is crucial to provide optimal treatment and access to LT.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 2","pages":"Pages 459-466"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388842","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":"Hepatic artery stenosis after pediatric liver transplantation: The potential role of conservative management","authors":"Weihao Li ,&nbsp;Thomai Kotsou ,&nbsp;Hermien Hartog ,&nbsp;Rene Scheenstra ,&nbsp;Vincent E. de Meijer ,&nbsp;Martin W. Stenekes ,&nbsp;Martijn V. Verhagen ,&nbsp;Reinoud P.H. Bokkers ,&nbsp;Hubert P.J. van der Doef","doi":"10.1016/j.dld.2024.09.021","DOIUrl":"10.1016/j.dld.2024.09.021","url":null,"abstract":"<div><h3>Aim</h3><div>This study aimed to investigate the outcomes and effectiveness of various treatment strategies in patients with hepatic artery stenosis (HAS) after pediatric liver transplantation (pLT).</div></div><div><h3>Methods</h3><div>This is a single center observational cohort study between January 1st, 2004 and August 1st, 2023, including pLT recipients aged &lt;18 years. The primary outcome was graft and patient survival. The secondary outcomes included incidence of biliary complications, technical success of surgery or endovascular therapy (EVT), and changes in liver function. The cut-off for early and late HAS was 14 days after pLT.</div></div><div><h3>Results</h3><div>Among a total of 327 pLT patients, 4 % (<em>n</em> = 13) developed HAS (<em>n</em> = 3 early; <em>n</em> = 10 late). Treatments included surgical revascularization for one early HAS, conservative management with anticoagulation for one early and four late HAS, and EVT for one early and six late HAS. Over a median follow-up of 28.2 months after the diagnosis of HAS, graft survival was 100 % and 83 % in early and late HAS groups, and patient survival reached 100 % in both groups. One graft loss occurred in the conservative group. Conversely, graft survival in the EVT group was 100 %.</div></div><div><h3>Conclusion</h3><div>The long-term outcomes of HAS after pLT are excellent. Both EVT and conservative management exhibited high graft survival rates for late HAS, with EVT achieving high technical success.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 2","pages":"Pages 502-511"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of endoscopist-directed nurse-administered sedation in an Italian referral hospital: An audit of 2 years and 19,407 procedures","authors":"R. Conigliaro ,&nbsp;F. Pigò ,&nbsp;M. Gottin ,&nbsp;G. Grande ,&nbsp;S. Russo ,&nbsp;S. Cocca ,&nbsp;M. Marocchi ,&nbsp;M. Lupo ,&nbsp;M. Marsico ,&nbsp;S. Sculli ,&nbsp;H. Bertani","doi":"10.1016/j.dld.2024.10.007","DOIUrl":"10.1016/j.dld.2024.10.007","url":null,"abstract":"<div><h3>Background and study aims</h3><div>Balanced propofol sedation (BPS) administered by adequately trained non-anaesthesiologist personnel has gained popularity in GI endoscopy because of its shorter procedure and recovery time, high patient satisfaction, and low rate of adverse events (AEs), despite being considered controversial. We report data from an audit of endoscopist-directed (ED) nurse-administered sedation in an Italian referral hospital.</div></div><div><h3>Patients and methods</h3><div>Consecutive endoscopic procedures performed between 2020 and 2022 were considered. Under the guidance of the endoscopist, the nurse administered midazolam/fentanyl, followed by a progressive top-up dosage of a 10–20 mg bolus of propofol to achieve moderate to deep sedation. The endoscopists and nurses were all certified in our hospital with a continuous and scheduled training from 2006.</div></div><div><h3>Results</h3><div>During the study period, a total of 19,407 examinations (7,803 EGDS, 10,439 colonoscopies, 77 PEG, 697 EUS, and 365 ERCP) and 14,415 patients were included. Of these, 29.4 % of patients were classified as ASA I, 66.5 % as ASA II, and 5.1 % as ASA III. Hypotension was recorded in 1,293 (6 %) examinations and bradycardia in 176 (0.9 %) patients. Eleven patients (0.06 %) had minor respiratory adverse events. Two patients (0.01 %) had major AEs requiring orotracheal intubation.</div></div><div><h3>Conclusions</h3><div>ED-BPS is safe in low-risk patients. Major AEs occurred in 0.01 % of procedures.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 2","pages":"Pages 630-635"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496948","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":"Duodenal gastric heterotopia diagnosed by spectral CT","authors":"Bo Duan,&nbsp;Ying Zhao,&nbsp;Hongliang Li,&nbsp;Qingyu Ji","doi":"10.1016/j.dld.2024.10.019","DOIUrl":"10.1016/j.dld.2024.10.019","url":null,"abstract":"","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 2","pages":"Pages 638-639"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544240","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":"Small bowel metastasis from pulmonary pleomorphic carcinoma","authors":"Kevin Sarti ,&nbsp;Marie-Cécile Nollevaux ,&nbsp;Jean-François Rahier","doi":"10.1016/j.dld.2024.10.023","DOIUrl":"10.1016/j.dld.2024.10.023","url":null,"abstract":"","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 2","pages":"Pages 640-641"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692638","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":"Autoimmunity in chronic HDV infection: results from the HDV Describe study cohort","authors":"G.P. Caviglia ,&nbsp;E. Dileo ,&nbsp;T. Manetta ,&nbsp;B. Donati Marello ,&nbsp;P. Merlach ,&nbsp;A. Loglio ,&nbsp;M. Viganò ,&nbsp;S. Fagiuoli ,&nbsp;P. Colombatto ,&nbsp;B. Coco ,&nbsp;A. Olivero ,&nbsp;G. Troshina ,&nbsp;A. Ciancio ,&nbsp;D. Angrisani ,&nbsp;G.G. Di Costanzo ,&nbsp;C.F. Magni ,&nbsp;S. Antinori ,&nbsp;G. Rizzardini ,&nbsp;V. Messina ,&nbsp;M. Milella ,&nbsp;M. Rizzetto","doi":"10.1016/j.dld.2025.01.094","DOIUrl":"10.1016/j.dld.2025.01.094","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic liver disease induced by hepatitis D virus (HDV) infection is associated with autoimmune manifestations.</div></div><div><h3>Aim</h3><div>The present study investigated the prevalence of autoantibodies (auto-ab) and their association with clinical and virologic features in patients with chronic HDV infection.</div></div><div><h3>Materials and Methods</h3><div>We studied 494 patients with chronic HDV infection from the HDV Describe study cohort. Non-organ-specific auto-ab (e.g., anti-nuclear auto-ab [ANA], anti-smooth muscle auto-ab [ASMA], anti-mitochondrial auto-ab [AMA], and anti-liver-kidney microsomal auto-ab [LKM]) were tested in diluted serum samples (1:80) by indirect immunofluorescence (IIF) on rat kidney/stomach/liver tissue slides (Euroimmun, Germany). Selected serum samples were analysed by immunoblot (IB) (Euroimmun, Germany) to detect antigen-specific auto-ab.</div></div><div><h3>Results</h3><div>The prevalence of ANA, ASMA, AMA, and LKM by IIF was 9.9% (n=49), 12.3% (n=61), 2.0% (n=10), and 1.8% (n=9), respectively. Among LKM+ patients, only one patient was LKM-1+ at IB. A high proportion of patients had anti-brush border auto-ab (n=99; 20.0%); 9 patients were anti-parietal cells auto-ab+, 1 was anti-reticulin auto-ab+, and 1 was anti-lysosome auto-ab+. ASMA+ was associated with liver cirrhosis (OR=2.00, 1.08–3.70) and HDV RNA &gt;3 Log IU/mL (OR=1.91, 1.03–3.52), whereas no association was observed between ASMA+ and ALT &gt;40 U/L (OR=1.12, 0.65–1.93). At multivariate analysis, ASMA+ resulted significantly associated with liver cirrhosis (OR=1.89, 1.01–3.51) independently from HDV RNA (OR=1.57, 1.01–2.42) and ALT (OR=1.22, 0.79–1.87).</div></div><div><h3>Conclusion</h3><div>The assessment of circulating auto-ab by IIF may represent a valuable and inexpensive tool for identifying patients with high HDV replication and advanced liver disease.</div><div>This research was supported by Gilead Sciences, Inc (study ID: IN-IT-980-6382).</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Pages S50-S51"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578344","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":"High burden of MASLD and metALD in People with HIV: a call for liver fibrosis screening prioritization","authors":"F. Cinque ,&nbsp;J. Milic ,&nbsp;R. Righetti ,&nbsp;D. Kablawi ,&nbsp;L.R. Ballesteros ,&nbsp;W. Elgretli ,&nbsp;M. Shengir ,&nbsp;B. Lebouché ,&nbsp;N. Kronfli ,&nbsp;M.B. Klein ,&nbsp;J. Bischoff ,&nbsp;A.L. Fracanzani ,&nbsp;A. Bandera ,&nbsp;R. Lombardi ,&nbsp;J.K. Rockstroh ,&nbsp;G. Guaraldi ,&nbsp;G. Sebastiani","doi":"10.1016/j.dld.2025.01.014","DOIUrl":"10.1016/j.dld.2025.01.014","url":null,"abstract":"<div><h3>Background</h3><div>Evidence suggests that metabolic dysfunction-associated steatotic liver disease (MASLD) has heightened severity in people with HIV (PWH). However, hepatology guidelines do not recognize HIV as a risk factor for MASLD and fibrosis. Most data rely on the outdated NAFLD nomenclature, emphasizing the need for research within the MASLD framework.</div></div><div><h3>Aim</h3><div>to assess the prevalence and factors associated with steatotic liver disease (SLD), its subcategories, and significant liver fibrosis in PWH.</div></div><div><h3>Methods</h3><div>We analyzed data from clinical centers in Canada, Italy and Germany on consecutive PWH undergoing unselected screening for SLD and liver fibrosis. SLD was defined as controlled attenuation parameter &gt;248 dB/m. MASLD was defined as SLD plus ≥1 cardiometabolic factor without alcohol intake &gt;20-30g/day. Metabolic dysfunction- and alcohol-associated liver disease (MetALD) was defined as SLD with ≥1 cardiometabolic factor and alcohol intake 20-60g/day. Alcohol-associated liver disease (ALD) was defined as SLD with alcohol intake &gt;60g/day. Cryptogenic SLD (cSLD) was defined as SLD without cardiometabolic risk factors or other causes of SLD. Significant liver fibrosis and cirrhosis were diagnosed by liver stiffness measurement &gt;8 kPa and &gt;13 kPa, respectively. Logistic regression was used to investigate factors associated with MASLD and fibrosis.</div></div><div><h3>Results</h3><div>Among 3,006 PWH (median age 53, 25% female, all on ART, 85% with undetectable HIV viral load), 14% had HCV coinfection and 3% had HBV coinfection. SLD, MASLD, MetALD, cSLD, and ALD prevalence were 43.4%, 26.2%, 9.8%, 5.2%, and 2.2%, respectively. Overall, 11.2% had significant fibrosis, and 3.5% had cirrhosis. PWH with MASLD and MetALD had a significantly higher prevalence of significant fibrosis and cirrhosis compared to those without SLD (Figure). In multivariable analysis, body mass index (OR 1.28, 95% CI: 1.21–1.32) and age &gt;50 (OR 1.47, 95% CI: 1.07–2.08) were independently associated with MASLD after adjusting for sex, duration of HIV infection, ALT, GGT, nadir CD4 &lt;200 cells/uL, and use of integrase inhibitors. Significant fibrosis was associated with age (OR 1.01, 95% CI: 1.00–1.06), male sex (OR 1.53, 95% CI: 1.13–2.25), MASLD (OR 2.55, 95% CI: 1.70–3.25), MetALD (OR 1.89, 95% CI: 1.17–2.99), integrase inhibitor use (OR 1.65, 95% CI: 1.17–2.24), nadir CD4 &lt;200 cells/uL (OR 1.45, 95% CI: 1.06–1.98), and HCV coinfection (OR 3.41, 95% CI: 2.46–4.71), while HBV coinfection was not.</div></div><div><h3>Conclusion</h3><div>The updated SLD definition reveals a high prevalence of significant liver fibrosis in PWH, driven by hepatic steatosis with metabolic alterations (MASLD and MetALD), HIV-related factors, and HCV coinfection. PWH should be globally recognized as a high-risk population for MASLD and prioritized for liver fibrosis screening.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Page S8"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578704","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":"Effect of Protease-Activated Receptor 2 inhibition by 1-Piperidinepropionic acid in lipid accumulation, inflammation and hepatocellular carcinoma development","authors":"P. Guerra ,&nbsp;G. Villano ,&nbsp;C.M. Rejano-Gordillo ,&nbsp;M. Ruvoletto ,&nbsp;A. Biasiolo ,&nbsp;S. Quarta ,&nbsp;P. Peña-SanFelix ,&nbsp;S. De Siervi ,&nbsp;S. Cagnin ,&nbsp;C. Turato ,&nbsp;M.L. Martínez-Chantar ,&nbsp;P. Pontisso ,&nbsp;A. Martini","doi":"10.1016/j.dld.2025.01.009","DOIUrl":"10.1016/j.dld.2025.01.009","url":null,"abstract":"<div><h3>Introduction</h3><div>Hepatocellular carcinoma (HCC) and Metabolic-Associated Steatohepatitis (MASH) are major challenges in modern hepatology. 1-Piperidinepropionic Acid (1-PPA) is a novel inhibitor of Protease-Activated Receptor 2 (PAR2), which is involved in inflammation, lipid accumulation and tumour development. This study aims to evaluate the effect of 1-PPA on liver steatosis, inflammation and HCC development.</div></div><div><h3>Materials</h3><div>C57BL/6J mice transgenic overexpressing SerpinB3 (C57/TG), fed on a CDAA diet and injected with diethylnitrosamine (DEN) were divided into two groups (n=8 each) and treated with 1-PPA or placebo. HCC development was confirmed by liver histology. Microsomal triglyceride transfer protein (MTP) activity was quantified in liver tissue using a specific assay. qPCR of macrophage M2-polarization markers was carried out. Human liver organoids were cultured with Oleic Acid and SB3, and treated with 1-PPA and lomitapide, an inhibitor of VLDL export. Lipid and ROS accumulation was quantified using BodiPY and MitoSOX respectively.</div></div><div><h3>Results</h3><div>C57/TG mice treated with 1-PPA developed a lower mean number of nodules (1.5 vs 5, p &lt; 0.05), a reduced mean tumoral mass (0.04 vs 0.1 g, p &lt; 0.01) and a blunted expression of M2-polarization macrophage markers. MTP activity was increased in the liver of mice treated with 1-PPA. Human liver organoids showed a significant increase in lipid and ROS accumulation after Oleic Acid administration. Treatment with 1-PPA significantly lower lipid and ROS accumulation, however contemporary treatment with lomitapide reverted this effect, suggesting a role in VLDL export.</div></div><div><h3>Conclusion</h3><div>1-PPA treatment reduced HCC development by reducing lipid accumulation and M2-macrophage polarization in a mouse model of NASH-induced liver carcinogenesis. 1-PPA treatment reduced lipid accumulation by stimulating VLDL formation and secretion both in a mouse model of MASH-induced liver carcinogenesis and in human liver organoids.</div></div>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"57 ","pages":"Pages S4-S5"},"PeriodicalIF":4.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578782","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}