Journal of Hepatology最新文献

{"title":"NUC-1031 in aBTC: a cautionary tale in accelerated drug development","authors":"Giulia Massaro, Lorenza Rimassa, Angela Lamarca","doi":"10.1016/j.jhep.2025.05.011","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.05.011","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Financial support</h2>The authors received no financial support to produce this manuscript.</section></section><section><section><h2>Authors' contributions</h2>GM, LR, and AL contributed to the concept of the letter. GM and AL interpreted the data and drafted the manuscript. All authors critically revised the manuscript and approved its final draft.</section></section><section><section><h2>Data availability statement</h2>Data are available on reasonable request.All authors confirm that we did not and will not submit the data included in the letter as original publication elsewhere.</section></section><section><section><h2>Declaration of Competing Interest</h2>AL: Travel and educational support from Ipsen, Pfizer, Bayer, AAA, SirtEx, Novartis, Mylan, Delcath Advanz Pharma and Roche. Speaker honoraria from Merck, Pfizer, Ipsen, Incyte, AAA/Novartis, QED, Servier, Astra Zeneca, EISAI, Roche, Advanz Pharma and MSD. Advisory and consultancy honoraria from EISAI, Nutricia, Ipsen, QED, Roche, Servier, Boston Scientific, Albireo Pharma, AstraZeneca, Boehringer Ingelheim, GENFIT, TransThera Biosciences, Taiho, MSD and Viatris. Principal</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"238 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122667","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":"Enteronephrohepatic Circulation of Bile Acids and Therapeutic Potential of Systemic Bile Acid Transporter Inhibitors","authors":"Ahmed Ghallab, Mattias Mandorfer, Guido Stirnimann, Joachim Geyer, Erik Lindström, Tom Luedde, Schalk van der Merwe, Jassin Rashidi-Alavijeh, Hartmut Schmidt, Saul J. Karpen, Peter Fickert, Michael Trauner, Jan G. Hengstler, Paul A. Dawson","doi":"10.1016/j.jhep.2025.05.009","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.05.009","url":null,"abstract":"Together with carriers in liver and small intestine, kidney transporters function to conserve and compartmentalize bile acids in the enteronephrohepatic circulation. In patients with liver disease, systemic bile acid levels are elevated, undergo increased renal glomerular filtration, and contribute to the pathogenesis of cholemic nephropathy and acute kidney injury. In this review, we describe mechanisms for renal bile acid transport and highlight very recent discoveries that challenge current paradigms for the pathogenesis of cholemic nephropathy and renal tubule cast formation. We also discuss the therapeutic potential of inhibiting the kidney apical sodium-dependent bile acid transporter (ASBT) to redirect bile acids into urine for elimination, reduce hepatobiliary accumulation and systemic levels of bile acids, and treat cholemic nephropathy. In conclusion, a deeper understanding of the enteronephrohepatic bile acid axis is providing insights into novel strategies to protect both liver and kidney in patients with liver disease.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"20 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122666","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":"Is MetALD an all-inclusive term for liver disease caused by alcohol and metabolic dysfunction?","authors":"Gyorgy Baffy, Emilie K. Mitten, Piero Portincasa","doi":"10.1016/j.jhep.2025.05.012","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.05.012","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors' contributions</h2>GB conceived the manuscript. All authors wrote, edited, and reviewed the final manuscript.</section></section><section><section><h2>Financial support</h2>The authors received no financial support to produce this manuscript.</section></section><section><section><h2>Declaration of Competing Interest</h2>The authors declare no conflicts of interest that pertain to this work.Please refer to the accompanying ICMJE disclosure forms for further details.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"28 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122670","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: “EUS-guided portal pressure measurement: Beware of thrombosis risk”","authors":"Wim Laleman ,&nbsp;Emma Vanderschueren ,&nbsp;Michael Praktiknjo","doi":"10.1016/j.jhep.2025.05.010","DOIUrl":"10.1016/j.jhep.2025.05.010","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"83 2","pages":"Pages e81-e83"},"PeriodicalIF":26.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122669","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":"Immune exclusion in hepatoblastoma: Is β-catenin to blame again?","authors":"Theo Z. Hirsch","doi":"10.1016/j.jhep.2025.05.005","DOIUrl":"10.1016/j.jhep.2025.05.005","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"83 2","pages":"Pages 286-289"},"PeriodicalIF":26.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114339","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 “Improving Risk Estimation in MASLD: Competing Events and Liver Function Reserve”","authors":"Axel Wester, Gabriel Issa, Hannes Hagström","doi":"10.1016/j.jhep.2025.05.006","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.05.006","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors' contributions</h2>Axel Wester drafted the manuscript. All authors critically reviewed the manuscript and approved it before submission.</section></section><section><section><h2>Financial support</h2>AW was supported by the Syskonen Svensson foundation for medical research (2021-00284), Mag-Tarmfonden, the Bengt Ihre foundation (SLS-973809, SLS-999079), the Professor Nanna Svartz foundation (2022-00448), Region Stockholm (CIMED) (FoUI-985859), and Gastroenterologisk forskningsfond (SLS-999141). HH was supported by grants from Region Stockholm (FoUI-960537), the Swedish Research Council (2021-01293), and the Swedish Cancer Society (2 2210 Pj 01 H). The funders had no role in the conduct of</section></section><section><section><h2>Declaration of Competing Interest</h2>HH:s institutions have received research funding from Astra Zeneca, EchoSens, Gilead, Intercept, MSD and Pfizer. HH has served as consultant for Astra Zeneca and has been part of hepatic events adjudication committees for KOWA and GW Pharma. The other authors declare no conflict of interests. Please refer to the accompanying ICMJE disclosure forms for further details.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"55 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097360","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":"Phosphatidylethanol-guided reclassification of steatotic liver disease subgroups improves prognostic stratification: Greater precision is required","authors":"Danna Xie, Baolin Qian, Qin Zeng","doi":"10.1016/j.jhep.2025.05.007","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.05.007","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>The influence of hematocrit (HCT) should be considered when detecting PEth</h2>As PEth is a derivative of red blood cell membrane phospholipids, its concentration is positively associated with HCT. In patients with dehydration (such as vomiting after alcohol) or anemia, HCT may abnormally increase or decrease, which in turn leads to overestimation or underestimation of PEth levels in the whole blood. A recent study found that a 10% fluctuation in HCT can alter whole-blood PEth values by 15%–20%, whereas washed erythrocyte assays can eliminate this interference</section></section><section><section><h2>The influence of PEth detection time and half-life should be considered when detecting PEth</h2>The study¹ indicates that PEth reflects alcohol consumption within 1–4 weeks, consistent with previous research.³ Notably, with the extension of the time since the last alcohol consumption (Free-alcohol time), the level of PEth gradually decreases. Hill-Kapturczak et al.⁴ demonstrated through pharmacokinetic modeling that blood PEth concentrations decrease by 50% when the Free-alcohol time was 7 days. This suggests that Free-alcohol time is very important for the level of PEth. Furthermore,</section></section><section><section><h2>Authors' contributions</h2>All authors contributed to the drafting and revision of this letter. These authors contribute equally to this work: Danna Xie and Baolin Qian.</section></section><section><section><h2>Data availability statement</h2>Data that support the findings of this study are available from the corresponding author upon reasonable request.</section></section><section><section><h2>Financial support</h2>This work was supported by grants from the National Natural Scientific Foundation of China (82400740) and Applied Basic Research Project of Southwest Medical University (2024ZKY050).</section></section><section><section><h2>Declaration of Competing Interest</h2>The authors of this study declare that they do not have any conflict of interest.Please refer to the accompanying ICMJE disclosure forms for further details.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"76 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097468","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":"In memoriam: Harry Dalton (17th December 1958-19th March 2024)","authors":"Eleanor Barnes ,&nbsp;Heiner Wedemeyer","doi":"10.1016/j.jhep.2025.03.016","DOIUrl":"10.1016/j.jhep.2025.03.016","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"83 1","pages":"Pages 5-7"},"PeriodicalIF":26.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066519","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":"JHEP at a glance (June 2025)","authors":"","doi":"10.1016/S0168-8278(25)00264-8","DOIUrl":"10.1016/S0168-8278(25)00264-8","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"82 6","pages":"Pages e275-e285"},"PeriodicalIF":26.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979772","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":"Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study","authors":"Do-Youn Oh, Aiwu Ruth He, Shukui Qin, Li-Tzong Chen, Takuji Okusaka, Jin Won Kim, Thatthan Suksombooncharoen, Myung Ah Lee, Masayuki Kitano, Howard A. Burris, Mohamed Bouattour, Suebpong Tanasanvimon, Renata Zaucha, Antonio Avallone, Juan Cundom, Aleksandra Kuzko, Julie Wang, Ioannis Xynos, Arndt Vogel, Juan W. Valle","doi":"10.1016/j.jhep.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.05.003","url":null,"abstract":"&lt;h3&gt;Background&lt;/h3&gt;At the TOPAZ-1 (NCT03875235) primary analysis, durvalumab plus gemcitabine and cisplatin (GemCis) significantly improved overall survival (OS) in advanced biliary tract cancer (aBTC). We report updated exploratory analyses of OS and safety, characterisation of extended long-term survivors (eLTS), and subsequent anticancer therapy (SAT) use.&lt;h3&gt;Methods&lt;/h3&gt;Participants with aBTC received durvalumab+GemCis or placebo+GemCis every 3 weeks (≤8 cycles), then durvalumab or placebo monotherapy every 4 weeks until progressive disease or other discontinuation criteria were met. OS and serious adverse events (SAEs) were assessed in the full analysis and safety analysis sets (FAS/SAS), respectively. eLTS outcomes were assessed (FAS participants alive ≥30 months after randomisation).&lt;h3&gt;Results&lt;/h3&gt;685 participants were randomised: durvalumab+GemCis (n = 341); placebo+GemCis (n = 344). After a median 41.3 (95% confidence interval [CI] 39.3–44.1) months’ follow-up in all participants, median OS (95% CI) for durvalumab+GemCis versus placebo+GemCis was 12.9 (11.6–14.1) versus 11.3 (10.1–12.5) months (hazard ratio, 0.74 [95% CI 0.63–0.87]); 36-month OS rate was 14.6% versus 6.9%, respectively. In participants who achieved disease control (566/685; 82.6%), the 36-month OS rate was higher for durvalumab+GemCis (17.0%) versus placebo+GemCis (7.6%). Overall, 12.8% were eLTS, with more eLTS in the durvalumab+GemCis (17.0%) versus placebo+GemCis (8.7%) arms; eLTS included all clinically relevant subgroups. Durvalumab+GemCis improved OS regardless of SAT use. In eLTS, SAEs were comparable between arms and less frequent than in the full SAS.&lt;h3&gt;Conclusions&lt;/h3&gt;Survival benefit and manageable safety continued with durvalumab+GemCis versus placebo+GemCis approximately 3 years after the last participant was randomised. All clinically relevant subgroups were represented in eLTS, supporting standard-of-care status for durvalumab+GemCis in aBTC.&lt;h3&gt;Lay summary&lt;/h3&gt;The TOPAZ-1 study found that treatment with durvalumab plus gemcitabine and cisplatin (chemotherapy, also known as GemCis), helped people with advanced biliary tract cancer (BTC) to live longer on average than those treated with a placebo plus GemCis. The latest results from TOPAZ-1 showed that these benefits continued for over 3 years in participants treated with durvalumab plus GemCis and side effects continued to be manageable. At an updated analysis, carried out 3 years after the last participant started the study, twice as many participants treated with durvalumab plus GemCis were alive compared to those treated with placebo plus GemCis. Results also showed that the positive effect of durvalumab plus GemCis compared with placebo plus GemCis was not affected by the use of other therapies some participants received after they finished the study treatment. These results continue to support durvalumab plus GemCis as a standard first-line treatment for people with advanced BTC.&lt;h3&gt;Clinical trial r","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"29 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066583","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}