Journal of Hepatology最新文献

{"title":"Barriers to Viral Hepatitis Elimination and New Strategies to Overcome Them in Low- and Middle-Income Countries","authors":"Erwan Vo-Quang,Maud Lemoine,Jean-Michel Pawlotsky","doi":"10.1016/j.jhep.2026.08.032","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.08.032","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"72 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum HBsAg cannot distinguish cccDNA activity from integrated HBV DNA expression in chronic hepatitis B virus infection.","authors":"Aleksei Suslov, Matthias S Matter, Diego Calabrese, Athimed El Taher, Stefan Wieland, Markus H Heim","doi":"10.1016/j.jhep.2026.08.018","DOIUrl":"10.1016/j.jhep.2026.08.018","url":null,"abstract":"<p><strong>Background & aims: </strong>HBsAg is currently used as the key serum biomarker to define functional cure of chronic hepatitis B. Declining HBsAg is often interpreted as evidence of covalently closed circular DNA (cccDNA) elimination or durable transcriptional silencing. However, HBsAg can also be produced from transcriptionally active HBV DNA integrated into the host genome (iDNA), which can make serum HBsAg an unreliable indicator of cccDNA activity or quantity.</p><p><strong>Methods: </strong>We combined intrahepatic HBsAg immunostaining, quantitative HBsAg (qHBsAg), and digital droplet PCR-based profiling of HBV DNA and RNA in liver biopsies to identify patients in whom HBsAg expression was predominantly driven by cccDNA or iDNA. We then compared HBsAg abundance, isoform composition, secretion, and intrahepatic staining patterns between these groups.</p><p><strong>Results: </strong>All three envelope proteins (L, M, and S) were detectable in liver tissue and serum in both groups. The relative abundance of L and S proteins, assessed by western blot and immunofluorescence, did not differ between iDNA- and cccDNA-driven cases. Across the combined cohort, intrahepatic HBsAg burden correlated with serum qHBsAg, indicating similar intracellular retention and secretion behaviour. Importantly, all established intrahepatic HBsAg staining patterns (membranous and cytoplasmic subtypes) occurred in both groups, with no pattern uniquely associated with either source.</p><p><strong>Conclusions: </strong>iDNA can sustain HBsAg expression profiles that are indistinguishable from those generated by active cccDNA. Serum HBsAg alone may therefore fail to identify patients who have achieved cccDNA elimination or durable transcriptional silencing. These findings suggest that the use of serum qHBsAg as a component of the functional cure endpoint in clinical studies should be re-evaluated.</p><p><strong>Impact and implications: </strong>Serum HBsAg is the central biomarker used to define and monitor \"functional cure\" in chronic hepatitis B. This study shows that in patients with substantial HBV DNA integration, HBsAg is produced predominantly from integrated sequences, and that integration-derived HBsAg is indistinguishable from cccDNA-derived HBsAg in isoform composition, secretion behaviour, and histological distribution. Long-read sequencing confirmed that the integrated sequences generate full-length envelope transcripts. These findings are most relevant to virologists, hepatologists, clinical trialists, and regulators developing and evaluating HBV cure strategies. They indicate that serum HBsAg measurement cannot report cccDNA burden or transcriptional activity, and that focusing on HBsAg loss could miss \"partial cure\" states with favourable clinical outcomes. This warrants re-evaluation of HBsAg loss as a main functional cure endpoint and supports the use of complementary or source-specific markers to assess treatment response.</p>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":40.1,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histology alone may underestimate liver cirrhosis despite adequate biopsy quality: evidence from minilaparoscopic liver biopsies.","authors":"Sonia-Emilia Selicean, Elsa Väisänen, Malte Wehmeyer, Peter Hübener, Ansgar W Lohse","doi":"10.1016/j.jhep.2026.08.014","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.08.014","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":40.1,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harmonizing ACLF definition: Why is it essential for scientific progress?","authors":"Anand V Kulkarni, Shiv Kumar Sarin, Ashok Choudhury, Paolo Angeli, Richard Moreau, Jasmohan Singh Bajaj","doi":"10.1016/j.jhep.2026.08.021","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.08.021","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":40.1,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elafibranor in primary biliary cholangitis: Two-year placebo-controlled outcomes and long-term open-label data from the ELATIVE® phase III trial.","authors":"Kris V Kowdley, Christopher L Bowlus, Cynthia Levy, Ulus Akarca, Mario Reis Alvares-da-Silva, Pietro Andreone, Marco Arrese, Christophe Corpechot, Hany Elbeshbeshy, Sven Francque, Michael A Heneghan, Pietro Invernizzi, Ira M Jacobson, David Jones, Andreas E Kremer, Frederik C Kruger, Marcelo Kugelmas, Eric Lawitz, Marlyn J Mayo, Mitchell L Shiffman, Mark Sonderup, Mark G Swain, José Miguel Valera, John M Vierling, Ares Villagrasa, Alejandra Villamil, Nuno Antunes, Claire Raskino, Marwan Sleiman, Valeria Cranham, Benjamin Miller, Jörn M Schattenberg","doi":"10.1016/j.jhep.2026.08.016","DOIUrl":"10.1016/j.jhep.2026.08.016","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background & aims: &lt;/strong&gt;We report 104-week placebo-controlled data and long-term open-label extension (OLE) data from the ongoing ELATIVE® phase III trial (NCT04526665) of elafibranor in primary biliary cholangitis (PBC).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 161 patients were randomized 2:1 to elafibranor 80 mg or placebo. The double-blind period (DBP) consisted of 52-week common (Part 1) and variable (Part 2) periods. Patients completing Part 1 continued into Part 2 until all patients completed Part 1, or for a maximum of 104 weeks. All patients completing Part 1 could enter the OLE and receive elafibranor.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;At Week 104 in DBP Part 2, 64.3% (18/28) and 10.7% (3/28) of elafibranor-treated patients achieved biochemical response and alkaline phosphatase (ALP) normalization, respectively, vs. no placebo-treated patients. In patients with moderate-to-severe fatigue or pruritus at baseline, mean (SE) changes to Week 104 in PROMIS Fatigue Short Form 7a (PFSF 7a) and PBC Worst-Itch Numeric Rating Scale (PBC WI NRS) were -6.3 (2.2) vs. -0.4 (1.2) and -4.1 (1.0) vs. 0.3 (1.2), respectively, with elafibranor vs. placebo. A total of 138 patients entered the OLE (continuous elafibranor: n = 93; crossover elafibranor: n = 45). Among patients continuing elafibranor, 58.8% (47/80) and 65.0% (13/20) achieved biochemical response, and 15.0% (12/80) and 25.0% (5/20) achieved ALP normalization at Weeks 104 and 156, respectively. In crossover patients, 51.2% (21/41) and 22.0% (9/41) achieved biochemical response and ALP normalization after 52 weeks, respectively. In patients continuing elafibranor with moderate-to-severe symptoms at baseline, mean (SE) changes to Week 130 in PFSF 7a and PBC WI NRS were -4.8 (1.5) and -4.0 (0.7), respectively. There were no unexpected safety findings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Through 3 years of treatment, elafibranor led to sustained biochemical improvements and was generally well tolerated, with numerical improvements in fatigue and pruritus.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Impact and implications: &lt;/strong&gt;Given the chronic, progressive nature of primary biliary cholangitis (PBC), the long-term efficacy and tolerability of treatments is important. Here, we present 2-year results from the double-blind period, and long-term data from the ongoing open-label extension of the phase III ELATIVE® trial, wherein elafibranor (a peroxisome proliferator-activated receptor-α/δ agonist) treatment led to sustained biochemical improvements, stable non-invasive tests of fibrosis, and numerical improvements in fatigue and pruritus, through 3 years. Elafibranor demonstrated a favorable safety profile up to a maximum treatment exposure of 3.5 years, including in patients crossing over from placebo. These findings support elafibranor as a durable long-term treatment for patients with PBC, and are particularly relevant for clinicians managing patients with inadequate response or intolerance to first-line tre","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":40.1,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: Correspondence on \"Longitudinal changes in cardiometabolic risk factors are associated with changes in liver stiffness in adults with MASLD\".","authors":"Matthew Dukewich, Jennifer L Dodge, Wendy Mack, Norah Terrault","doi":"10.1016/j.jhep.2026.08.013","DOIUrl":"10.1016/j.jhep.2026.08.013","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":40.1,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing cure following treatment for hepatitis C among people who inject drugs: Where to next?","authors":"Jason Grebely, Graham R Foster","doi":"10.1016/j.jhep.2026.08.022","DOIUrl":"10.1016/j.jhep.2026.08.022","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":40.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic steatosis as an architect of CRC metastatic niche.","authors":"Valerie Chew","doi":"10.1016/j.jhep.2026.08.002","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.08.002","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":40.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can we de-escalate HCC surveillance after 10 years of HBV suppression on nucleos(t)ide analogues?","authors":"Wen-Juei Jeng, Anna S F Lok","doi":"10.1016/j.jhep.2026.08.023","DOIUrl":"10.1016/j.jhep.2026.08.023","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":40.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol, cardiometabolic risk factors, and cirrhosis: Ten-year risk estimates from a population-based Danish cohort.","authors":"Jonas Hedelund Rønn, Peter Jepsen, Jessica Mellinger, Hamish Innes, Marie Holm Eliasen, Anne Illemann Christensen, Lone Galmstrup Madsen, Gro Askgaard","doi":"10.1016/j.jhep.2026.08.017","DOIUrl":"10.1016/j.jhep.2026.08.017","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background & aims: &lt;/strong&gt;The combined effects of alcohol consumption and cardiometabolic risk factors on cirrhosis risk are increasingly recognized. We examined the independent and combined associations of alcohol consumption and cardiometabolic risk factors with cirrhosis risk.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We included 354,624 participants from the Danish National Health Surveys 2010-2017 without a diagnosis of cirrhosis. We estimated 10-year absolute and relative cirrhosis risks, population attributable fractions (PAFs), and supra-additive interactions according to alcohol consumption and cardiometabolic risk factors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Participants had a median age of 55 years; 12% reported ≥15 drinks/week, 17% had a BMI ≥30 kg/m&lt;sup&gt;2&lt;/sup&gt;, 5% had diabetes, 28% had hypertension, 21% smoked, and 18% had dyslipidemia. During 3.3 million person-years of observation, 1,211 developed cirrhosis. Alcohol consumption strongly affected the risk of cirrhosis (10-year absolute risks of 0.14%, 0.29%, 0.68%, 2.0% and 4.6% for 1-7, 8-14, 15-28, 29-42, and &gt;42 drinks per week, respectively). BMI ≥30 kg/m&lt;sup&gt;2&lt;/sup&gt;, diabetes, hypertension, and smoking were each associated with two-to threefold higher risk. Dyslipidemia was not associated with cirrhosis risk overall but was associated with increased risk among participants drinking 8-14 drinks/week. BMI ≥30 kg/m&lt;sup&gt;2&lt;/sup&gt;, diabetes, and hypertension increased risk among consumers of 1-28 drinks per week but not for &gt; 28 drinks/week. Smoking increased risk across all alcohol levels, with indications of supra-additive interaction. PAFs were 59.9% for alcohol consumption, 29.3% for hypertension, 21.2% for smoking, 13.8% for BMI ≥30 kg/m&lt;sup&gt;2&lt;/sup&gt;, and 9.0% for diabetes; dyslipidemia had no statistically significant PAF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Obesity, diabetes, hypertension, and smoking, but not dyslipidemia, increased cirrhosis risk, with modest effects compared to heavy alcohol use. The impact of cardiometabolic risk factors was non-significant above 28 drinks per week, underscoring alcohol as the principal driver of cirrhosis risk in heavy drinkers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Impact and implications: &lt;/strong&gt;The introduction of the MetALD nomenclature has highlighted the need to understand how alcohol consumption and cardiometabolic risk factors jointly contribute to cirrhosis risk, but whether these interactions differ by level of alcohol intake has remained unclear. In this population-based cohort, alcohol consumption was the dominant modifiable risk factor, with approximately 60% of cirrhosis cases attributable to drinking above the minimum-risk reference range, whereas the attributable fractions for individual cardiometabolic and lifestyle risk factors were substantially smaller. Supra-additive associations were observed for obesity, diabetes, and hypertension, mainly at alcohol intakes of up to 28 drinks/week, whereas smoking showed a supra-additive association with a","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":40.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}