Journal of Hepatology最新文献

{"title":"The complexity of portal hypertension without (apparent) cirrhosis","authors":"Ansgar W. Lohse, Patrick S. Kamath, Shiv K. Sarin","doi":"10.1016/j.jhep.2025.02.011","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.02.011","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Data availability statement (delete if not applicable)</h2>n/a</section></section><section><section><h2>Authors' contributions</h2>AWL, PSK and SKS wrote, reviewed and edited the manuscript.</section></section><section><section><h2>Financial support</h2>No financial support</section></section><section><section><h2>Declaration of Competing Interest</h2>nonePlease refer to the accompanying ICMJE disclosure forms for further details.</section></section><section><section><h2>Acknowledgements</h2>n/a</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"23 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451639","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":"Ruptured HCC: An entity in exile from EASL Clinical Practice Guideline!","authors":"Dhiraj Agrawal, Guru N. Reddy","doi":"10.1016/j.jhep.2025.02.017","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.02.017","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors' contributions</h2>DA, Initial draft, revision, and editingGNR, Revision, and Final approval</section></section><section><section><h2>Financial support</h2>Nothing to report</section></section><section><section><h2>Declaration of Competing Interest</h2>Nothing to report</section></section><section><section><h2>Acknowledgements</h2>None</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"64 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451598","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":"Both the timing of the measurement and the adjustment of the portal pressure gradient (PPG) after TIPS implantation are important.","authors":"Alexander Zipprich, Philipp Reuken, Andreas Stallmach, Cristina Ripoll","doi":"10.1016/j.jhep.2025.01.041","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.01.041","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Data availability statement (delete if not applicable)</h2>Data available more in detail in Reference 2 and by request from the corresponding author.</section></section><section><section><h2>Authors' contributions</h2>Zipprich, A: conception; analysis and interpretation of the data, drafting of the article. Reuken, P: analysis of the data, critical revision for important intellectual content. Stallmach, A: critical revision for important intellectual content. Ripoll, C: drafting of the article, critical revision for important intellectual content.</section></section><section><section><h2>Financial support</h2>No financial support.</section></section><section><section><h2>Declaration of Competing Interest</h2>AZ received lecture and consulting fee from Falk, CSL Behring, Gore. PAR received lecture and consulting fees from Pfizer, BMS, Gilead, Advanz and CSL Behring. CR received lecture and/or consulting fees from Falk, CSL Behring, Gore, Grifols and Ingelheim-Boehringer.Please refer to the accompanying ICMJE disclosure forms for further details.</section></section><section><section><h2>Acknowledgements</h2>N.a.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"63 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451638","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":"Revisiting the use of albumin in patients with cirrhosis – trial design matters","authors":"Ann T. Ma, Adrià Juanola, Cristina Solé, Pere Ginès","doi":"10.1016/j.jhep.2025.02.009","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.02.009","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Authors' contributions</h2>All authors contributed equally to the production of this manuscript.</section></section><section><section><h2>Financial support</h2>None.</section></section><section><section><h2>Declaration of Competing Interest</h2>PG has received research funding from Gilead and Grifols. PG has consulted or attended advisory boards for Gilead, RallyBio, SeaBeLife, Merck, Sharp and Dohme (MSD), Ocelot Bio, Behring, Roche Diagnostics International, Boehringer Ingelheim and Astra-Zeneca, and received speaking fees from Pfizer. The other authors have declared no conflict of interest.Please refer to the accompanying ICMJE disclosure forms for further details.</section></section><section><section><h2>Acknowledgements</h2>None.</section></section>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"15 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451640","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":"Developing splice-switching oligonucleotides for urea cycle disorder using an integrated diagnostic and therapeutic platform","authors":"Jin Rong Ow, Eri Imagawa, Feng Chen, Wei Yuan Cher, Shermin Yu Tung Chan, Rajasekhar Reddy Gurrampati, Venkataramanan Ramadass, Mun Fai Loke, Tommaso Tabaglio, Hikaru Nishida, Toshiki Tsunogai, Masahide Yazaki, Gaik Siew Ch’ng, Manikandan Lakshmanan, Su Seong Lee, Jackie Yi-ru Ying, Ernesto Guccione, Kimihiko Oishi, Keng Boon Wee","doi":"10.1016/j.jhep.2025.02.007","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.02.007","url":null,"abstract":"<h3>Backgrounds &amp; Aims</h3>Citrin deficiency (CD) is an autosomal recessive urea cycle disorder caused by biallelic loss-of-function variants in the <em>SLC25A13</em> gene, leading to life-threatening hyperammonemia and hypoglycemia. Variants in deep introns can cause genetic diseases by altering splicing and are often missed by current diagnostic tools. Splice-switching oligonucleotides (SSOs) can resolve certain intronic variants, but patients harboring such variants need to be identified. We present a lean workflow from molecular diagnostics to SSO development to resolve splice-altering variants in deep introns that is applicable to other genetic disorders.<h3>Methods</h3>A deep intronic gene panel was designed to identify deep intronic variants. SSOs were then developed and validated <em>in vitro</em> using minigene assay and induced hepatocytes, and target engagement was verified <em>in vivo</em> by hydrodynamic tail vein injection of minigenes and SSOs.<h3>Results</h3>With the Deep Intronic-Gene Panel and RNA analysis, we identified a novel <em>SLC25A13</em> c.469-2922G&gt;T variant that promotes the inclusion of a premature stop codon-containing pseudo-exon, SLC25A13-PE5, thereby causing CD. By a stepwise rational SSO design approach, we identified potent candidates inhibiting SLC25A13-PE5 at EC₅₀ &lt;2nM <em>in vitro</em>. Upon conjugating the SSOs with N-acetylgalactosamine (GalNAc), they were validated to rescue normal protein expression and restore ureagenesis and ammonia clearance, key urea cycle functions, in patient-derived induced hepatocytes. <em>In vivo</em> on-target efficacy of the clinical GalNAc-SSO candidate, in the absence of acute toxicity and inflammation, was observed in a mouse model with exogenous hepatic minigene expression.<h3>Conclusions</h3>Our data validates a platform to redefine molecular diagnosis of urea cycle disorders and provides a proof-of-concept for precision therapy of CD patients whose only effective treatment is liver transplantation.<h3>IMPACT &amp; IMPLICATIONS</h3>Deep intronic variants are common causes of genetic diseases that are commonly neglected. In this study, we demonstrate an integrated precision diagnostic and therapeutic approach for UCD. Specifically, we focus on CD, going from the discovery of a novel splice variant in the <em>SLC25A13</em> gene with our novel UCD Deep Intronic-Gene Panel, to the development and <em>in vivo</em> validation of an efficacious SSO candidate for the pathogenic splice variant. We envision the possibility of extrapolating this pipeline to the diagnosis and development of treatments for other rare genetic diseases.","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"49 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451642","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":"A phase III randomised study of first-line NUC-1031/cisplatin vs. gemcitabine/cisplatin in advanced biliary tract cancer","authors":"Jennifer J. Knox, Mairéad G. McNamara, Igor S. Bazin, Do-Youn Oh, Oleksii Zubkov, Valeriy Breder, Li-Yuan Bai, Alan Christie, Lipika Goyal, David P. Cosgrove, Christoph Springfeld, Katrin M. Sjoquist, Joon Oh Park, Helena Verdaguer, Chiara Braconi, Paul J. Ross, Aimery De Gramont, Rachna T. Shroff, John R. Zalcberg, Daniel H. Palmer, Juan W. Valle","doi":"10.1016/j.jhep.2025.01.040","DOIUrl":"https://doi.org/10.1016/j.jhep.2025.01.040","url":null,"abstract":"&lt;h3&gt;Background and Aims&lt;/h3&gt;The previous first-line standard of care for advanced biliary tract cancer (aBTC), gemcitabine/cisplatin, had modest efficacy. NUC-1031 is a phosphoramidate modification of gemcitabine. We report final analyses of the NuTide:121 study, designed to compare the efficacy of NUC-1031/cisplatin to gemcitabine/cisplatin in aBTC.&lt;h3&gt;Methods&lt;/h3&gt;In this open-label, multicenter study, adult patients with treatment-naïve aBTC were randomized (1:1) to NUC-1031/cisplatin (n=388) or gemcitabine/cisplatin (n=385) on Days 1 and 8 of 21-day cycles until disease progression or intolerance. Primary endpoints were overall survival (OS) and objective response rate (ORR; blinded independent central review). Three interim analyses (IA) and a final analysis were planned.&lt;h3&gt;Results&lt;/h3&gt;Baseline characteristics were balanced; median age 65 years, 53% male, primary tumors: intra-hepatic cholangiocarcinoma (CCA) (54%), extra-hepatic CCA (21%), gallbladder (21%) and ampullary cancer (5%). Enrollment stopped at IA1 as the OS futility boundary was crossed. At final data cut-off, median OS for NUC-1031/cisplatin vs gemcitabine/cisplatin was 9.2 months (95%CI: 8.3–10.4) vs 12.6 months (95%CI: 11.0–15.1) (HR 1.79) and median PFS was 4.9 months (95%CI: 4.4–6.0) vs 6.4 months (95%CI: 6.1–7.4) (HR 1.45). ORR was higher for NUC-1031/cisplatin (18.7% vs 12.4%; OR: 1.59; p=0.049). The adverse event profile was similar between arms, except for hepatobiliary disorders (25% vs 11%; higher with NUC-1031/cisplatin) and hematological events (48% vs 65%; higher with gemcitabine/cisplatin). More patients met criteria for potential drug-induced liver injury (27% vs 7%) and Hy’s law (1.6% vs 0.5%) with NUC-1031/cisplatin. Treatment exposure was lower for NUC-1031/cisplatin, likely due to early discontinuation for AEs (30% vs 18%).&lt;h3&gt;Conclusions&lt;/h3&gt;NuTide:121 was terminated early due to futility. NUC-1031/cisplatin did not set a new standard in first-line aBTC.&lt;h3&gt;Trial Registration&lt;/h3&gt;ClinicalTrials.gov Identifier: NCT04163900&lt;h3&gt;Impact and Implications&lt;/h3&gt;Advanced biliary tract cancers remain in need of substantial therapeutic improvement. Although clinical practice guidelines identified gemcitabine plus cisplatin as the standard of care on the basis of clinical studies, the modest efficacy observed with this regimen highlighted the urgent need for more effective therapies. NuTide:121, one of the largest randomized interventional studies conducted in the first-line aBTC population to date, compared the combination of cisplatin with NUC-1031, a phosphoramidate form of gemcitabine, with the standard of care regimen. Despite a higher response rate in the NUC-1031/cisplatin arm, the study was terminated early based on a futility assessment of OS. Early toxicity and in particular liver injury likely contributed to the regimen's failure. This study emphasized some important challenges in study design and further confirmed the difficulties of advancing treatment optio","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"81 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451643","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 EASL Guidelines app is your indispensable mobile companion for accessing comprehensive and up-to-date clinical practice guidelines in hepatology. Download it now!","authors":"","doi":"10.1016/S0168-8278(25)00029-7","DOIUrl":"10.1016/S0168-8278(25)00029-7","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"82 3","pages":"Page iii"},"PeriodicalIF":26.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417416","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":"EASL Congress 2025: prepare and submit your late-breaker!","authors":"","doi":"10.1016/S0168-8278(25)00028-5","DOIUrl":"10.1016/S0168-8278(25)00028-5","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"82 3","pages":"Page ii"},"PeriodicalIF":26.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417419","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 THRIVE project aims to understand tumor-host interactions in adult and childhood liver cancer to develop response biomarkers and new therapies","authors":"","doi":"10.1016/S0168-8278(25)00031-5","DOIUrl":"10.1016/S0168-8278(25)00031-5","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"82 3","pages":"Page v"},"PeriodicalIF":26.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417417","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":"Join the community and become an EASL member today!","authors":"","doi":"10.1016/S0168-8278(25)00030-3","DOIUrl":"10.1016/S0168-8278(25)00030-3","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"82 3","pages":"Page iv"},"PeriodicalIF":26.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417418","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}