Hepatology最新文献

{"title":"Reply: AASLD Resmetirom Guidance.","authors":"Vincent L Chen, Timothy R Morgan, Yaron Rotman, Heather M Patton, Kenneth Cusi, Fasiha Kanwal, W Ray Kim","doi":"10.1097/HEP.0000000000001267","DOIUrl":"10.1097/HEP.0000000000001267","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E164-E165"},"PeriodicalIF":12.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412591","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 real-world outcomes with obeticholic acid in primary biliary cholangitis (HEROES): A trial emulation study design.","authors":"M Alan Brookhart, Tracy J Mayne, Charles Coombs, Alexander Breskin, Erik Ness, Leona Bessonova, Yucheng Julia Chu, Jing Li, Michael W Fried, Bettina E Hansen, Kris V Kowdley, David Jones, George Mells, Palak J Trivedi, Shaun Hiu, Dorcas N Kareithi, James Wason, Rachel Smith, John D Seeger, Gideon M Hirschfield","doi":"10.1097/HEP.0000000000001174","DOIUrl":"10.1097/HEP.0000000000001174","url":null,"abstract":"<p><strong>Background and aims: </strong>Primary biliary cholangitis is a rare, progressive liver disease. Obeticholic acid (OCA) received accelerated approval for treating patients with primary biliary cholangitis in whom ursodeoxycholic acid failed, based on a surrogate endpoint of reduction in ALP. Analysis of the long-term safety extension with 2 external control groups demonstrated a significant increase in event-free survival in OCA-treated patients. This fully real-world evidence study assessed the effect of OCA treatment on clinical outcomes.</p><p><strong>Approach and results: </strong>This trial emulation used data from the Komodo Healthcare Map claims database linked to US national laboratory, transplant, and death databases. Patients with compensated primary biliary cholangitis and intolerance/inadequate response to ursodeoxycholic acid who initiated OCA therapy were compared with patients who were OCA-eligible but not OCA-treated. The primary endpoint was time to the first occurrence of death, liver transplant, or hospitalization for hepatic decompensation, analyzed using a propensity-score weighted Cox proportional hazards model. Baseline prognostic factors were balanced using standardized morbidity ratio weighting. For the primary analysis, 4174 patients contributed 11,246 control index dates, and 403 patients contributed OCA indexes. Weighted groups were well balanced. Median (95% CI) follow-up in the OCA and non-OCA arms was 9.3 (8.4-10.6) months and 17.5 (16.2-18.6) months (weighted population; censored at discontinuation). Eight events occurred in the OCA arm and 32 in the weighted control (HR = 0.37; 95% CI = 0.14-0.75; p < 0.001). Effects were consistent for each component of the composite endpoint.</p><p><strong>Conclusions: </strong>We identified a 63% reduced risk of hospitalization for hepatic decompensation, liver transplant, or death in OCA-treated versus non-OCA-treated individuals.</p><p><strong>Trial registration: </strong>HEROES; ClinicalTrials.gov NCT05292872.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"1647-1659"},"PeriodicalIF":12.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12077331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Reciprocal regulation of microRNA-122 and c-Myc in hepatocellular cancer: Role of E2F1 and transcription factor dimerization partner 2.","authors":"Bo Wang, Shu-Hao Hsu, Xinmei Wang, Huban Kutay, Hemant Kumar Bid, Jianhua Yu, Ramesh K Ganju, Samson T Jacob, Mariia Yuneva, Kalpana Ghoshal","doi":"10.1097/HEP.0000000000001261","DOIUrl":"10.1097/HEP.0000000000001261","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"E176"},"PeriodicalIF":12.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770816","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":"Erratum: Nonphagocytic activation of NOX2 is implicated in progressive nonalcoholic steatohepatitis during aging.","authors":"Joy X Jiang, Sarah R Fish, Alexey Tomilov, Yuan Li, Weiguo Fan, Ali Dehnad, David Gae, Suvarthi Das, Gergely Mozes, Gregory W Charville, Jon Ramsey, Gino Cortopassi, Natalie J Török","doi":"10.1097/HEP.0000000000001324","DOIUrl":"10.1097/HEP.0000000000001324","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"81 6","pages":"E180"},"PeriodicalIF":12.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092399","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":"Retraction: C-Jun mediates hepatitis C virus hepatocarcinogenesis through signal transducer and activator of transcription 3 and nitric oxide-dependent impairment of oxidative DNA repair.","authors":"Keigo Machida, Hidekazu Tsukamoto, Jian-Chang Liu, Yuan-Ping Han, Sugantha Govindarajan, Michael M C Lai, Shizuo Akira, Jing-Hsiung James Ou","doi":"10.1097/HEP.0000000000001226","DOIUrl":"10.1097/HEP.0000000000001226","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"81 6","pages":"E181"},"PeriodicalIF":12.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092402","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":"Galectin-1 modulates glycolysis via a GM1-galactose-dependent pathway to promote hyperthermia resistance in hepatocellular carcinoma.","authors":"Tu Nguyen,Yonghwan Shin,Aravinth Ruppa,Abigail S Krall,Janet Pham,Po-Chun Chen,Hannah Mirmohammadi,Pedram Keshavarz,Richard S Finn,Vatche G Agopian,Samuel W French,Heather R Christofk,David S K Lu,Steven S Raman,Jason Chiang","doi":"10.1097/hep.0000000000001391","DOIUrl":"https://doi.org/10.1097/hep.0000000000001391","url":null,"abstract":"BACKGROUND AND AIMSThermal ablation is the standard of care treatment modality with curative intent for early-stage non-resectable hepatocellular carcinoma (HCC), but a durable response is limited-with up to 40% of HCC patients eventually experiencing local recurrence on post-treatment surveillance. While thermal ablation has been established to cause immediate cell death in the center of the thermal ablation zone, its metabolic impact in the peri-ablational region remains unclear. We aimed to elucidate the metabolic mechanism by which Galectin-1 (Gal-1) promotes thermal-ablation-induced hyperthermia resistance in HCC and demonstrate the therapeutic potential of inhibiting Gal-1 in combination with thermal ablation in vivo.APPROACH AND RESULTSProteomic analysis was performed using an untargeted approach on pre-ablation formalin-fixed paraffin-embedded (FFPE) biopsy specimens of thermal ablation responders (n=32) and nonresponders (n=23). Gal-1 was found to be overexpressed in thermal ablation nonresponders compared to responders. Moreover, HCC with Gal-1 overexpression demonstrated reduced sensitivity to hyperthermia in vitro and increased utilization of glycolysis and downstream TCA cycle under hyperthermia-induced stress. Gal-1-overexpressing HCC enhanced its metabolic utilization through Gal-1-facilitated GM1-ganglioside breakdown, producing galactose to increase the metabolic influxes into glycolysis and consequently the downstream TCA cycle. In vivo studies showed that inhibiting Gal-1 in combination with thermal ablation significantly reduced tumor size compared to either monotherapy thermal ablation or Gal-1 inhibition alone.CONCLUSIONSGal-1 can mediate hyperthermia resistance in HCC and can potentially be modulated as a therapeutic target to reduce rapid progression after thermal ablation.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"20 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122086","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":"Erratum: Effects of trientine and penicillamine on intestinal copper uptake: A mechanistic 64Cu PET/CT study in healthy humans.","authors":"Frederik Teicher Kirk, Ditte Emilie Munk, Eugene Scott Swenson, Adam Michael Quicquaro, Mikkel Holm Vendelbo, Michael L Schilsky, Peter Ott, Thomas Damgaard Sandahl","doi":"10.1097/HEP.0000000000001367","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001367","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148747","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":"Management of Immune Tolerant Chronic Hepatitis B.","authors":"Mai M Kilany,Milan J Sonneveld,Jordan J Feld,Harry L A Janssen","doi":"10.1097/hep.0000000000001407","DOIUrl":"https://doi.org/10.1097/hep.0000000000001407","url":null,"abstract":"The immune-tolerant (IT) phase of chronic hepatitis B (CHB) is a distinct stage of infection, characterized by high hepatitis B virus (HBV) replication, normal alanine aminotransferase (ALT) levels, and minimal liver inflammation. Despite its classification as a benign phase, growing evidence challenges this notion, revealing immune activation, HBV DNA integration, and potential oncogenic processes even in the absence of elevated ALT. The IT phase's prolonged high viral replication raises concerns about its implications for hepatocellular carcinoma (HCC) risk. Histological studies show that significant inflammation and fibrosis may exist in patients meeting IT criteria, suggesting that the current definitions may underestimate disease activity. Treatment during the IT phase remains controversial, with international guidelines largely recommending against antiviral therapy due to its limited efficacy and potential risks. However, subsets of IT patients may benefit from early intervention. The risks and benefits of therapy in IT CHB are not fully understood, and the lack of consensus regarding treatment thresholds further complicates clinical decision-making. This review highlights the importance of redefining IT CHB to include virological and histological parameters and calls for long-term studies to clarify the role of therapy in reducing fibrosis progression and HCC risk. A more precise understanding of the IT phase is essential to balance the risks of treatment against its potential benefits and to inform future therapeutic strategies.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"55 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103552","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":"TATA-box binding protein associated factor 2 (TAF2) in hepatocyte survival and tumorigenesis","authors":"Saranya Chidambaranathan Reghupaty, Suchismita Raha, Rachel Mendoza, Debashri Manna, Ali Gawi Ermi, Eva Davis, Younus Aqeel, Mark A. Subler, Jennifer Koblinski, Michael Idowu, Nitai Mukhopadhyay, Zhao Lai, Paul B. Fisher, Jolene J. Windle, Mikhail G. Dozmorov, Devanand Sarkar","doi":"10.1097/hep.0000000000001406","DOIUrl":"https://doi.org/10.1097/hep.0000000000001406","url":null,"abstract":"Chromosome 8q amplification is a frequent event in cancers including hepatocellular carcinoma (HCC). TATA-box binding protein Associated Factor 2 (TAF2), a component of Transcription Factor IID (TFIID) residing in 8q24.12, is amplified in HCC. As yet, a potential oncogenic function of TAF2 in HCC has not been documented. We identified TAF2 mRNA and protein overexpression in human HCC cells and tissue samples, compared to their normal counterparts. A significant negative correlation between TAF2 levels and overall survival of HCC patients was observed. The role of TAF2 in HCC regulation was examined using a hepatocyte-specific conditional knockout mouse (Taf2<jats:sup>ΔHEP</jats:sup>), TAF2 knockdown and overexpressing human HCC cells, and TAF2 overexpression in mouse liver by hydrodynamic approach. As a core component of basal transcription machinery, TAF2 is required for hepatocyte survival. As such, in Taf2<jats:sup>ΔHEP</jats:sup> mice there were hepatocyte death and compensatory proliferation, contributing to an inflammatory/fibrotic milieu favoring HCC. Accordingly, N-nitrosodiethylamine (DEN)/high fat high sugar diet-induced HCC was robustly augmented in Taf2<jats:sup>ΔHEP</jats:sup> mice compared to their wild-type littermates. TAF2 overexpression in mouse liver did not lead to tumor development, but significantly augmented HCC that was induced by overexpression of the driver oncogene MYC. TAF2 augmented cancer hallmarks in human HCC cells by binding to the promoters of tumor promoting genes and non-coding RNAs and regulating their transcription. Thus, TAF2 plays a unique and central role in hepatocyte survival and tumorigenesis.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"6 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097469","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":"Suppressing MASH fibrotic progression by blocking succinate-GPR91 signaling in hepatic stellate cells","authors":"Li Xie, Hui Chen, Li Zhang, Yong-Yu Yang, Yuan Zhou, Yue Ma, Chang Liu, Yu-Li Wang, Qin Zhu, Ya-Jun Yan, Jia Ding, Ning-Ping Zhang, Qiang Deng, Xiu-Ping Liu, Wei Jiang, Jian Wu","doi":"10.1097/hep.0000000000001405","DOIUrl":"https://doi.org/10.1097/hep.0000000000001405","url":null,"abstract":"Background: The succinate receptor GPR91 is highly expressed in hepatic stellate cells (HSCs), with its expression further elevated during metabolic-dysfunction-associated steatohepatitis (MASH)-induced fibrotic progression. However, convincing in vivo data on whether blocking GPR91 signaling leads to fibrotic regression in MASH is lacking. Methods: MASH models were induced by choline-deficient amino acid-defined diet feeding along with lipopolysaccharide injection (CDAA-LPS) plus intraperitoneal injection of succinate or by high-fat and high-calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) in wild-type (WT) mice and HSC-specific GPR91 knockout (HSC-GPR91-KO) mice. Results: Administration of succinate significantly exacerbated fibrosis in CDAA-fed WT mice, as evidenced by increased collagen deposition and hydroxyproline levels along with an increased GPR91 expression in activated HSCs. Both WT and HSC-GPR91-KO mice exhibited substantial elevation in hepatic succinate levels upon HFCD-HF/G diet feeding. However, in comparison to HFCD+HF/G-fed WT mice, hepatic fibrosis was markedly ameliorated in HSC-GPR91-KO mice, as evidenced by diminished hepatic hydroxyproline content with downregulated fibrogenic markers. Succinate stimulation led to an increase in α-SMA, GPR91, phosphorylated ERK1/2, c-jun and Smad3 protein levels and enhanced the molecular interaction between c-jun and Smad3, inhibited forskolin-induced cAMP production in human HSCs, and increased p-NF-κB transcriptional activity, thereby suppressing HSC apoptosis. Conclusions: HSC-specific GPR91 receptor deficiency effectively halted hepatic fibrosis, probably through two distinct signaling pathways: suppressing the succinate-GPR91-Gβγ-ERK/c-jun-smad3 axis that positively regulates HSC activation; and abrogating the GPR91-Gαi-cAMP-NF-κB pathway that hinders their apoptosis. These findings confer GPR91 as a promising target for molecular interventions in blocking MASH-fibrotic progression.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"33 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097470","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}