Hepatology最新文献

{"title":"Telehealth versus in-person early palliative care for patients with cirrhosis: An ancillary study from the multi-center PAL-LIVER trial","authors":"Marina Serper, Andrzej Kosinski, Victor Navarro, Richard Kalman, Manisha Verma","doi":"10.1097/hep.0000000000001860","DOIUrl":"https://doi.org/10.1097/hep.0000000000001860","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"19 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890194","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":"Drug-induced liver injury (DILI) in clinical trials: Views and practical updates from DILI specialists at FDA.","authors":"Paul H Hayashi, Mark I Avigan","doi":"10.1097/HEP.0000000000001858","DOIUrl":"10.1097/HEP.0000000000001858","url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) continues to be a significant challenge in drug development. Just 1 or 2 cases of severe hepatotoxicity in a clinical trial can be enough to raise drug approval concerns. Though great strides were made in DILI risk assessment and mitigation in clinical trials during the early 2000s, drugs continue to fail in development due to DILI, while severe cases still occur in late-phase clinical trials and post-market. Also, changes in drug development will challenge the US Food and Drug Administration's (FDA) current paradigms for DILI risk assessment. Such changes include the rise in biologic agents, which may cause hepatotoxicity distinctly different from small-molecule drugs, the increasing reliance on smaller, underpowered clinical trials for rare diseases, and the growing interest in drugs for acute and chronic liver diseases. We highlight eight key topics that may benefit from review, clarification, research, and discussion between industry, academia, and regulators as the FDA works to address these issues.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885978","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":"Clinical utility of a 30% reduction in VCTE-derived liver stiffness measurement for identifying histologic improvement in MASH.","authors":"Rohit Loomba, Ruiqiu Chen, Youxin Wang, Ricki Bettencourt, Egbert Madamba, Kaleb Tesfai, Lisa Richards, Mark Muthiah, Eunice Tan, Dan Yock Young, Mildred D Gottwald, Shibao Feng, Maya Margalit, Daniel Q Huang","doi":"10.1097/HEP.0000000000001856","DOIUrl":"10.1097/HEP.0000000000001856","url":null,"abstract":"<p><strong>Background and aims: </strong>The American Association for the Study of Liver Diseases (AASLD) recommends that a decline in liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) can be used as a non-invasive endpoint for treatment response in metabolic dysfunction-associated steatohepatitis (MASH), but there are limited data supporting this statement. We examined the association between a ≥30% relative decline in LSM and fibrosis regression.</p><p><strong>Approach and results: </strong>This prospective study included 160 adults (64% female) with biopsy-proven MASH and stage 2-3 fibrosis from a randomized, phase 2b, multicenter, placebo-controlled trial of the fibroblast growth factor 21 analog pegozafermin. All participants underwent contemporaneous VCTE assessments and liver biopsy at 2 time points. The primary endpoint was fibrosis regression without worsening MASH. The median (IQR) age and body mass index of participants were 56.0 (49.0-62.0) years and 36.5 (32.2-40.4) kg/m 2 . The area under the receiver operating curve (AUC) of a ≥30% relative decline in LSM by VCTE for detecting fibrosis regression was 0.68 (95% CI 0.58-0.77). In multivariable analyses adjusted for age, sex, type 2 diabetes, BMI, and ethnicity, a ≥30% relative decline in LSM was independently associated with fibrosis regression (adjusted OR 4.23, 95% CI 1.79-10.38, p =0.001). In a distinct validation cohort (n=48) from the United States and Singapore, a ≥30% decline in LSM for detecting fibrosis regression yielded an AUC of 0.62 (95% CI 0.48-0.76).</p><p><strong>Conclusion: </strong>A ≥30% relative decline in LSM by VCTE had modest accuracy to detect fibrosis regression without worsening MASH. More effective biomarkers for treatment response are required.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885947","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":"Light across the Pacific Ocean: An Asian perspective on BEACON-HCC.","authors":"Thomas Yau, Man-Fung Yuen, Tan-To Cheung","doi":"10.1097/HEP.0000000000001857","DOIUrl":"10.1097/HEP.0000000000001857","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885963","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":"Genetic regulation of CPEB3-mediated alternative polyadenylation associated with survival of patients with hepatocellular carcinoma.","authors":"Haoxue Wang, Shanshan Zhang, Chenhui Zhang, Huan Liu, Qian Shen, Siyue Wang, Pengcheng Liu, Cong Zhang, Qing Wang, Jie Tang, Huiying Liu, Jing Gong, Jipin Jiang, Xiaoping Miao, Rong Zhong","doi":"10.1097/HEP.0000000000001859","DOIUrl":"10.1097/HEP.0000000000001859","url":null,"abstract":"<p><strong>Background: </strong>Alternative polyadenylation (APA) is a key post-transcriptional mechanism that regulates gene expression by modulating 3'UTR length; its dysregulation has been implicated in carcinogenesis. How genetic variants influence APA to affect hepatocellular carcinoma (HCC) prognosis remains unclear.</p><p><strong>Methods: </strong>Prognosis-APA quantitative trait loci (apaQTL) were performed using genotype and APA profiling from TCGA data. A two-stage survival analysis in 848 Chinese and 369 TCGA LIHC patients and functional validation were used to identify prognostic apaQTL in HCC progression.</p><p><strong>Results: </strong>A total of 2025 and 817 significant APA events were identified in the Chinese and TCGA cohorts, respectively. Besides, 859 events were associated with poor prognosis in HCC and enriched in RNA splicing/metabolism pathways. We detected 32,034 significant apaQTLs, predominantly enriched in 3'UTRs and RBP-binding regions. CPEB3 was prioritized as a key APA regulator RBP; its low expression correlated with poor patient survival and promoted proliferation, migration, and invasion in HCC cells. Notably, a functional apaQTL variant rs2037547, located in GSK3B and mediated by CPEB3, demonstrated a poor survival of HCC patients in both cohorts (pooled HR=1.29, p =0.016). Mechanistically, rs2037547 promoted aberrant APA at proximal poly(A) sites of GSK3B through CPEB3, leading to increased expression of short 3'UTR isoform. This regulatory alteration enhanced HCC cell proliferation, invasion, and migration, and contributed to HCC progression.</p><p><strong>Conclusion: </strong>These findings elucidated the distinct role of apaQTL-mediated APA dysregulation in HCC prognosis, providing insights for prognostic stratification and potential targets for personalized therapy in HCC.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872397","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":"Beyond cirrhosis: Major adverse liver outcomes across homozygous and heterozygous alpha-1 antitrypsin deficiency-associated liver disease.","authors":"Dustin Bastaich, Bassam Dahman, Austen Hentschel, Chitra Karki, Tami Nussbaum, Suna Park, May Hagiwara, Seth A Spector, Gregory E Bigford, Brian Garnet, Michael Campos, Binu V John","doi":"10.1097/HEP.0000000000001854","DOIUrl":"10.1097/HEP.0000000000001854","url":null,"abstract":"<p><strong>Background and aims: </strong>Alpha-1 antitrypsin deficiency (AATD) may cause chronic lung and liver disease, yet data on major adverse liver outcomes (MALO) across heterozygous and homozygous Z allele genotypes remain limited. We assessed the risk of MALO across AATD Pi*MZ, Pi*SZ, and Pi*ZZ genotypes compared with the wildtype Pi*MM.</p><p><strong>Approach and results: </strong>This retrospective cohort study utilized the Veterans Analysis of Liver Disease cohort (January 2000-April 2025). Genotypes were identified using validated natural language processing (κ=0.89). Multivariable Fine-Gray models estimated the hazard of MALO. Among 22,537 participants with genotype testing (19,665 Pi*MM, 1656 Pi*MZ, 281 Pi*SZ, and 935 Pi*ZZ) and 352,612 person-years of follow-up, MALO risk increased sequentially with allele burden: Pi*MZ (aHR 1.25, 1.11-1.40), Pi*SZ (aHR 1.51, 1.17-1.94), and Pi*ZZ (aHR 1.80, 1.57-2.07), versus Pi*MM. MALO incidence rates for Pi*MM, Pi*MZ, Pi*SZ, and Pi*ZZ were 11.3, 13.0, 14.6, and 19.2 per 1000 person-years, respectively, while 5-year MALO probability was 3.5%, 5.5%, 5.3%, and 8.1%, respectively. Pi*ZZ was associated with significantly increased risk of all individual MALO components: decompensation, HCC, liver transplantation (LT), and liver-related death (LRD). Pi*SZ and Pi*MZ were associated with a higher risk of decompensation, LT, and LRD, but not HCC. A sensitivity analysis restricted to participants with MASLD showed consistent findings.</p><p><strong>Conclusion: </strong>In this national longitudinal cohort of veterans with documented AATD genotype testing and a median follow-up of 15.9 years, we observed an increased risk of MALO in both homozygous and heterozygous Z-allele carriers, underscoring the need for timely diagnosis and enhanced clinical surveillance among veterans with known AATD genotypes.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849577","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":"BEACON-HCC through the lens of a large U.S. multidisciplinary program","authors":"Matthew S. Johnson, John H. Holden, Anita A. Turk","doi":"10.1097/hep.0000000000001850","DOIUrl":"https://doi.org/10.1097/hep.0000000000001850","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"126 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148821188","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":"Safety and efficacy of zetomipzomib in relapsed or insufficiently responding autoimmune hepatitis: Results from the randomized, double-blind, placebo-controlled, phase 2a PORTOLA study and open-label extension.","authors":"Craig S Lammert, Ethan M Weinberg, Seth N Sclair, Robert J Fontana, Neel K Anand, Janet L Anderl, David Bade, Shraddha Desai, Christopher J Kirk, Diana Lam, Eric Lowe, Tony Muchamuel, Kiruthi Palaniswamy, Rachel Peterson, Kathryn Ray, Zung To, Brian B Tuch, Jennifer A Whang, Aparna Goel","doi":"10.1097/HEP.0000000000001840","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001840","url":null,"abstract":"<p><strong>Background and aims: </strong>Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease with limited treatments and a need for glucocorticoid-sparing therapies. Zetomipzomib is a selective immunoproteasome inhibitor in development for AIH.</p><p><strong>Approach and results: </strong>PORTOLA was a randomized, double-blind, placebo-controlled, phase 2a trial at 24 US centers evaluating weekly subcutaneous zetomipzomib (60 mg) versus placebo in adults with AIH and active disease despite ≥3 months of standard-of-care therapy or flare after remission. Participants completing the 24-week period could enter a 24-week open-label extension (OLE). The primary endpoint was complete biochemical remission [CR: normalized liver enzymes and immunoglobulin G (if elevated), glucocorticoid dose ≤baseline] by week 24, assessed in the full analysis set (FAS) and steroid-based subgroup [intention-to-treat (ITT)]; safety was evaluated in all treated participants (NCT05569759). Between April 20, 2023, and July 2, 2024, 24 participants were randomized; 23 (zetomipzomib n=16, placebo n=7) comprised the FAS. By week 24, CR occurred in 50% zetomipzomib and 42.9% placebo participants (difference: 7.1% [95% CI: -38.5, 48.3]); 37.5% of zetomipzomib participants achieved CR with a steroid taper to ≤5 mg/day versus 14.3% with placebo. In the ITT steroid-based subgroup (n=21), CR occurred in 57.1% zetomipzomib versus 28.6% placebo participants (28.6%; -20.2, 65.4); only zetomipzomib participants achieved CR with taper to ≤5 mg/day (42.9%). Common adverse events (AEs) were injection site reactions (93.8% vs. 57.1%) and systemic injection reactions (75% vs. 14.3%). Three zetomipzomib participants (18.8%) discontinued due to AEs; serious AEs occurred in 2 zetomipzomib and 1 placebo participant, not drug-related. OLE safety was consistent, with no serious AEs.</p><p><strong>Conclusion: </strong>Zetomipzomib resulted in numerically higher CR rates than placebo, with evidence of steroid-sparing activity in a difficult-to-treat population, and warrants evaluation in larger randomized studies.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149014897","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":"The road less traveled: Mapping the complex trajectories of PSC-IBD","authors":"Mian B. Khalid","doi":"10.1097/hep.0000000000001812","DOIUrl":"https://doi.org/10.1097/hep.0000000000001812","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"66 1","pages":"621-622"},"PeriodicalIF":13.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754717","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":"One cancer, four personalities: Transcriptomic signatures reveal molecular subtypes of advanced biliary tract cancer","authors":"Muhammed Dogukan Aksu","doi":"10.1097/hep.0000000000001813","DOIUrl":"https://doi.org/10.1097/hep.0000000000001813","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"11 1","pages":"623-624"},"PeriodicalIF":13.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754710","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}