Hepatology最新文献

{"title":"Assessing HCC risk in HBV inderminate phase.","authors":"Muhammad Osama Saeed,Sadia Paracha,Rahmat Ail,Syed Muhammad Ali Akbar,Hafiz Muhammad Tousif Afzal","doi":"10.1097/hep.0000000000001520","DOIUrl":"https://doi.org/10.1097/hep.0000000000001520","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"49 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025454","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":"Natural history and development of a novel composite endpoint in patients with alcohol-associated Hepatitis: Data from a prospective multicenter study.","authors":"Srinivasan Dasarathy,Wanzhu Tu,Nicole Welch,Samer Gawrieh,Yunpeng Yu,Qing Tang,Carla Kettler,Arun J Sanyal,Gyongyi Szabo,Vijay H Shah,Ramon Bataller,Laura E Nagy,Craig McClain,Naga Chalasani,Thomas Kerr,Mack Mitchell, ","doi":"10.1097/hep.0000000000001513","DOIUrl":"https://doi.org/10.1097/hep.0000000000001513","url":null,"abstract":"BACKGROUNDThe clinical course and outcomes of alcohol-associated hepatitis (AH) remain poorly understood. Major adverse liver outcomes (MALO) do not capture the added risk of return to drinking (RTD). We examined the natural history of AH and developed a composite endpoint using a contemporary observational cohort of AH.METHODSA cohort of 1127 participants: 712 AH patients, 256 heavy drinking (HD) controls without clinically evident liver disease, and 159 healthy controls, were prospectively followed for 6-months at eight United States centers as part of the Alcoholic Hepatitis Network (AlcHepNet) consortium. Outcomes included mortality and a composite endpoint (AlcHepNet composite index) that included death, liver transplantation, hepatic decompensation (new onset/worsening ascites, hepatic encephalopathy, variceal bleeding), liver-related hospital admission, MELD increase ≥5, and return to drinking (RTD).RESULTSOf 712 AH patients (age 45±10.7 y; 59.1% male), 558 (79.0%) had severe and 148 (21.0%) had moderate AH, 232 (32.5%) died, and 86 (12.1%) underwent liver transplantation. Mortality rates in moderate AH and severe AH were 0.7% versus 17.2% (30 d), 3.4% versus 26.5% (90 d), and 8.8% versus 30.5% (180 d), respectively (all p<0.001). Composite liver/alcohol use events were noted in 459 (64.5%) AH patients. Higher MELD score, lower mean arterial pressure, and baseline leukocytosis were associated with higher 90-day mortality in AH (all p<0.05). College education and higher alkaline phosphatase were associated with lower mortality. HD controls had low mortality (n=3; 1.2%).DISCUSSIONThis large observational study showed a high incidence of composite liver and alcohol-use events within six months, reiterating the need for early interventions.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"44 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025455","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":"Letter to the Editor: Clarifying the impact of response criteria and locoregional therapy on complete response outcomes in patients with hepatocellular carcinoma following immunotherapy","authors":"Tsung-Hao Liu, Hung-Chih Yang","doi":"10.1097/hep.0000000000001459","DOIUrl":"https://doi.org/10.1097/hep.0000000000001459","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"103 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995347","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":"Integrative hepatology: Enhancing overall health to manage liver disease.","authors":"Jennifer C Lai,Elliot Tapper,Puneeta Tandon","doi":"10.1097/hep.0000000000001516","DOIUrl":"https://doi.org/10.1097/hep.0000000000001516","url":null,"abstract":"Despite remarkable advances in diagnostics, pharmacotherapy, and transplantation, conventional hepatology often falls short in addressing the persistent symptoms, impaired quality of life, and broader health needs of people living with chronic liver disease. Integrative Hepatology-rooted in the principles of integrative medicine-offers a holistic, evidence-informed approach that combines conventional hepatology with complementary modalities to address the biological, nutritional, physical, psychosocial, behavioral, and environmental determinants of liver health. This framework emphasizes multimodal, patient-centered care aimed at improving both liver-specific and overall health outcomes. We outline three models for implementation: (1) foundational knowledge for all hepatologists, incorporating core skills in nutrition, physical activity, and mind-body practices; (2) collaborative referral networks to integrative health providers; and (3) specialized hepatologists with advanced training in integrative medicine. Examples of application to fatigue, cramps, falls, and mental health in chronic liver disease illustrate the potential for non-pharmacologic and complementary strategies to enhance patient well-being. Implementation faces challenges, including evidence gaps, limited training, time constraints, reimbursement barriers, and inequitable access, but opportunities exist through education, interdisciplinary collaboration, group medical visits, and digital health delivery. By expanding the scope of liver care to include whole-person health, Integrative Hepatology seeks not to replace established therapies but to augment their impact-supporting patients in achieving optimal health across the disease spectrum.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"31 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960112","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":"Letter to the Editor: Revisiting FOXP3 Expression and its prognostic implications in hepatocellular carcinoma.","authors":"Laizhu Zhang,Huan Li,Weiwei Zong,Binghua Li,Decai Yu","doi":"10.1097/hep.0000000000001512","DOIUrl":"https://doi.org/10.1097/hep.0000000000001512","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"36 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960117","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 the Letter to the Editor: Revisiting FOXP3 expression and its prognostic implications in hepatocellular carcinoma.","authors":"Chien-Hao Huang,Wei-Ting Ku,Tsung-Han Wu,Po-Ting Lin,Wei Teng,Chao-Wei Lee,Wen-Juei Jeng,Wei-Ting Chen,Chen-Chun Lin,Shi-Ming Lin,Yung-Chang Lin,Chun-Yen Lin","doi":"10.1097/hep.0000000000001515","DOIUrl":"https://doi.org/10.1097/hep.0000000000001515","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"29 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960111","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":"Value of HCC surveillance in a landscape of emerging surveillance options: Perspectives of a multi-stakeholder modified Delphi panel.","authors":"Amit G Singal, Lisa Quirk, Justin Boike, Victoria Chernyak, Ziding Feng, Giamarqo Giamarqo, Fasiha Kanwal, George N Ioannou, Sarah Manes, Jorge A Marrero, Neil Mehta, Anjana Pillai, Nicholas J Shaheen, Aasma Shaukat, Claude B Sirlin, Elizabeth Verna, Sachin Wani, Andrea Wilson Woods, Ju Dong Yang, Neehar D Parikh","doi":"10.1097/HEP.0000000000001203","DOIUrl":"10.1097/HEP.0000000000001203","url":null,"abstract":"<p><p>HCC surveillance is recommended by liver professional societies but lacks broad acceptance by several primary care and cancer societies due to limitations in the existing data. We convened a diverse multidisciplinary group of cancer screening experts to evaluate current and future paradigms of HCC prevention and early detection using a rigorous Delphi panel approach. The experts had high agreement on 21 statements about primary prevention, HCC surveillance benefits, HCC surveillance harms, and the evaluation of emerging surveillance modalities. The experts agreed that current data have methodologic limitations as well as unclear generalizability to Western populations. Although a randomized clinical trial of surveillance versus no surveillance is unlikely feasible, they concurred that alternative designs, such as a comparison of 2 surveillance modalities, could provide indirect evidence of surveillance efficacy. The panel acknowledged the presence of surveillance harms, but concurred the overall value of surveillance appears high, particularly given a greater emphasis on benefits over harms by both patients and clinicians. The experts underscored the importance of a framework for measuring both benefits and harms when evaluating emerging surveillance strategies. The panel acknowledged performance metrics of emerging methods may differ from other cancer screening programs given differences in populations, including higher risk of cancer development and competing risk of morality, and differences in diagnostic workflow in patients at risk of HCC. These data provide insights into the perceived value of HCC surveillance in an era of emerging blood- and imaging-based surveillance strategies.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"82 3","pages":"794-809"},"PeriodicalIF":15.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937437","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":"Adjuvant and neoadjuvant therapies for hepatocellular carcinoma.","authors":"Arndt Vogel, Robert C Grant, Tim Meyer, Gonzalo Sapisochin, Grainne M O'Kane, Anna Saborowski","doi":"10.1097/HEP.0000000000000726","DOIUrl":"10.1097/HEP.0000000000000726","url":null,"abstract":"<p><p>Immune-oncology-based regimens have shown efficacy in advanced HCC and have been implemented as standard of care as first-line therapy. Their efficacy, including high response rates, and safety justify their evaluation in earlier disease stages. Following negative results for adjuvant sorafenib in the global STORM trial in 2015, 4 global phase 3 trials, featuring different immune checkpoint inhibitor combinations, entered in parallel the race in the adjuvant setting. The IMbrave050 trial, comparing adjuvant atezolizumab in combination with bevacizumab to active surveillance following curative-intent resection or ablation, was the first to report, fast-tracking the results of the first interim analysis and demonstrating an improvement in recurrence-free survival. The trial has provoked a discussion on the horizon of expectations from adjuvant treatment and the clinical relevance of efficacy endpoints. Moreover, major pathological responses reported from early phase 2 data in the neoadjuvant setting provide a strong rationale for the evaluation of these concepts in phase 3 trials. In this review, we summarize current evidence and outline future directions for systemic therapies in early-stage HCC.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":"777-793"},"PeriodicalIF":15.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138796766","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":"Early on-treatment LSM reliably predicts liver-related events in CHB patients with significant fibrosis and cirrhosis","authors":"Yameng Sun, Shuyan Chen, Xiaoqian Xu, Hongxin Piao, Guofeng Chen, Wei Jiang, Yongpeng Chen, Mingyi Xu, Huiguo Ding, Wen Xie, Xiaoyuan Xu, Hui Ma, Anlin Ma, Tongtong Meng, Jialing Zhou, Bingqiong Wang, Mengyang Zhang, Xiaojuan Ou, Xinyan Zhao, Jidong Jia, Xiaoning Wu, Hong You","doi":"10.1097/hep.0000000000001504","DOIUrl":"https://doi.org/10.1097/hep.0000000000001504","url":null,"abstract":"Background: Evidence comparing longitudinal liver stiffness measurements (LSM) dynamics to on-treatment LSM for predicting clinical outcomes in patients receiving etiology therapy is limited. Objective: This study aimed to assess the prognostic value of on-treatment LSM in patients with chronic hepatitis B (CHB) receiving antiviral therapy. Design: Patients with CHB and significant fibrosis or cirrhosis were included in this prospective cohort. Liver-related events (LREs) were defined as hepatic decompensations, liver transplantation, or liver-related death. Association between LREs and baseline, on-treatment, and dynamic changes in LSM were analyzed. Results: A total of 1116 patients with CHB, including 875 (78.4%) diagnosed with cirrhosis, were followed for a median of 7.5 (2.5–9.5) years. On-treatment LSM was the most reliable predictor of 3- and 5-year outcomes (AUROC: 0.72–0.78) after 1–3 years of antiviral therapy, outperforming baseline LSM (AUROC: 0.59–0.65) and LSM changes (AUROC: 0.42–0.65). Patients with LSM &lt;10 kPa at 1, 2, or 3 years of antiviral therapy have a much lower risk of LREs, with a 5-year cumulative incidence of 2.2%, 2.6%, and 2.7%, respectively. This finding held true in cirrhosis subgroup, in validation cohort, and for predicting decompensations alone. Notably, patients with on-treatment LSM &lt;10 kPa showed better restoration of lobular architecture assessed by liver biopsies. Conclusions: On-treatment LSM measured 1 to 3 years after antiviral therapy offers superior predictive accuracy for LREs compared to baseline or LSM changes, with LSM &lt;10 kPa indicating a significantly lower risk, likely due to improved lobular architecture.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"30 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923864","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":"Human-induced pluripotent stem cell-based hepatic modeling of lipid metabolism-associated TM6SF2-E167K variant.","authors":"Lanuza A P Faccioli, Yiyue Sun, Olamide Animasahun, Takashi Motomura, Zhenghao Liu, Takeshi Kurihara, Zhiping Hu, Bo Yang, Zeliha Cetin, Annalisa M Baratta, Ajay Shankaran, Minal Nenwani, Leyla Nurcihan Altay, Linqi Huang, Noah Meurs, Jonathan Franks, Donna Stolz, Dillon C Gavlock, Mark T Miedel, Alina Ostrowska, Rodrigo M Florentino, Ira J Fox, Deepak Nagrath, Alejandro Soto-Gutierrez","doi":"10.1097/HEP.0000000000001065","DOIUrl":"10.1097/HEP.0000000000001065","url":null,"abstract":"<p><strong>Background and aims: </strong>TM6SF2 rs58542926 (E167K) is related to an increased prevalence of metabolic dysfunction-associated steatotic liver disease. Conflicting mouse study results highlight the need for a human model to understand this mutation's impact. This study aims to create and characterize a reliable human in vitro model to mimic the effects of the TM6SF2-E167K mutation for future studies.</p><p><strong>Approach and results: </strong>We used gene editing on human-induced pluripotent stem cells from a healthy individual to create cells with the TM6SF2-E167K mutation. After hepatocyte-directed differentiation, we observed decreased TM6SF2 protein expression, increased intracellular lipid droplets, and total cholesterol, in addition to reduced VLDL secretion. Transcriptomics revealed the upregulation of genes involved in lipid, fatty acid, and cholesterol transport, flux, and oxidation. Global lipidomics showed increased lipid classes associated with endoplasmic reticulum (ER) stress, mitochondrial dysfunction, apoptosis, and lipid metabolism. In addition, the TM6SF2-E167K mutation conferred a proinflammatory phenotype with signs of mitochondria and ER stress. Importantly, by facilitating protein folding within the ER of hepatocytes carrying TM6SF2-E167K mutation, VLDL secretion and ER stress markers improved.</p><p><strong>Conclusions: </strong>Our findings indicate that induced hepatocytes generated from human-induced pluripotent stem cells carrying the TM6SF2-E167K recapitulate the effects observed in human hepatocytes from individuals with the TM6SF2 mutation. This study characterizes an in vitro model that can be used as a platform to identify potential clinical targets and highlights the therapeutic potential of targeting protein misfolding to alleviate ER stress and mitigate the detrimental effects of the TM6SF2-E167K mutation on hepatic lipid metabolism.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"82 3","pages":"638-654"},"PeriodicalIF":15.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11865362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937478","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}