IF 13.5 1区医学

Hepatology Pub Date : 2026-09-04 DOI: 10.1097/hep.0000000000001860

Marina Serper, Andrzej Kosinski, Victor Navarro, Richard Kalman, Manisha Verma

引用次数: 0

Drug-Induced Liver Injury (DILI) in clinical trials: Views and practical updates from DILI specialists at FDA. 临床试验中的药物性肝损伤（DILI）： FDA DILI专家的观点和实践更新

IF 18 1区医学

Hepatology Pub Date : 2026-09-02 DOI: 10.1097/HEP.0000000000001858

Paul H Hayashi, Mark I Avigan

引用次数: 0

Clinical utility of a 30% reduction in VCTE-derived liver stiffness measurement for identifying histologic improvement in MASH. vcte衍生的肝硬度测量减少30%用于确定MASH组织学改善的临床应用。

IF 18 1区医学

Hepatology Pub Date : 2026-09-02 DOI: 10.1097/HEP.0000000000001856

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

{"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":"https://doi.org/10.1097/HEP.0000000000001856","url":null,"abstract":"Background and aims: 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.Approach and results: 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 two 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/m². 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 U.S. and Singapore, a ≥30% decline in LSM for detecting fibrosis regression yielded an AUC of 0.62 (95% CI 0.48-0.76).Conclusion: 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.","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}

引用次数: 0

Light across the pacific ocean: An asian perspective on BEACON-HCC. 横跨太平洋的光：亚洲人对BEACON-HCC的看法。

IF 18 1区医学

Hepatology Pub Date : 2026-09-02 DOI: 10.1097/HEP.0000000000001857

Thomas Yau, Man-Fung Yuen, Tan-To Cheung

引用次数: 0

Genetic regulation of CPEB3-mediated alternative polyadenylation associated with survival of patients with hepatocellular carcinoma. cpeb3介导的选择性聚腺苷酸化与肝癌患者生存相关的遗传调控

IF 18 1区医学

Hepatology Pub Date : 2026-09-01 DOI: 10.1097/HEP.0000000000001859

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

{"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":"https://doi.org/10.1097/HEP.0000000000001859","url":null,"abstract":"Background: 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.Methods: 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.Results: A total of 2,025 and 817 significant APA events were identified in Chinese and TCGA cohort, 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 cohort (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.Conclusion: 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.","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}

引用次数: 0

Beyond cirrhosis: Major adverse liver outcomes across homozygous and heterozygous Alpha-1 antitrypsin deficiency associated liver disease. 肝硬化之外：纯合子和杂合子α -1抗胰蛋白酶缺乏相关肝病的主要不良肝脏结局

IF 18 1区医学

Hepatology Pub Date : 2026-08-28 DOI: 10.1097/HEP.0000000000001854

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

{"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":"https://doi.org/10.1097/HEP.0000000000001854","url":null,"abstract":"Background: 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 remains limited. We assessed the risk of MALO across AATD Pi*MZ, Pi*SZ, and Pi*ZZ genotypes compared to the wildtype Pi*MM.Methods: 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.Results: Among 22,537 participants with genotype testing (19,665 Pi*MM, 1,656 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 for 1,000 person-years respectively, while five-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 higher risk of decompensation, LT, and LRD, but not HCC. A sensitivity analysis restricted to participants with MASLD showed consistent findings.Conclusion: In this national longitudinal cohort of veterans with documented AATD genotype testing and 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.","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}

引用次数: 0

BEACON-HCC through the lens of a large U.S. multidisciplinary program 通过美国一个大型多学科项目的镜头来观察BEACON-HCC

IF 13.5 1区医学

Hepatology Pub Date : 2026-08-27 DOI: 10.1097/hep.0000000000001850

Matthew S. Johnson, John H. Holden, Anita A. Turk

引用次数: 0

The road less traveled: Mapping the complex trajectories of PSC-IBD 少有人走过的路：绘制PSC-IBD的复杂轨迹

IF 13.5 1区医学

Hepatology Pub Date : 2026-08-19 DOI: 10.1097/hep.0000000000001812

Mian B. Khalid

引用次数: 0

One cancer, four personalities: Transcriptomic signatures reveal molecular subtypes of advanced biliary tract cancer 一种癌症，四种性格：转录组特征揭示晚期胆道癌的分子亚型

IF 13.5 1区医学

Hepatology Pub Date : 2026-08-19 DOI: 10.1097/hep.0000000000001813

Muhammed Dogukan Aksu

引用次数: 0

Erratum: NK-cell–elicited gasdermin-D–dependent hepatocyte pyroptosis induces neutrophil extracellular traps that facilitate HBV-related acute-on-chronic liver failure 勘误：nk细胞引起的气真皮蛋白d依赖性肝细胞焦亡诱导中性粒细胞胞外陷阱，促进hbv相关的急性慢性肝衰竭

IF 13.5 1区医学

Hepatology Pub Date : 2026-08-19 DOI: 10.1097/hep.0000000000001816

Qiang Zhao, Dong-Ping Chen, Hua-Di Chen, Ying-Zhe Wang, Wei Shi, Yi-Tong Lu, Yi-Zheng Ren, Yuankai Wu, Yi-Hua Pang, Hong Deng, Xiaoshun He, Dong-Ming Kuang, Zhiyong Guo

引用次数: 0

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