Laura Izquierdo-Sanchez, Jone Narbaiza, Julen Martin-Robles, Angela Lamarca, Heinz-Josef Klümpen, Adelaida La Casta, Arun Valsan, Stephanie Roessler, Chiara Braconi, Leonardo G da Fonseca, Cristina Dopazo, August T Juliebø, Ezequiel Mauro, Stefan Buettner, Domingo Balderramo, Mariano Ponz-Sarvise, Javier Díaz Ferrer, Krzysztof Zieniewicz, Kirsten Utpatel, Zeno Sparchez, Raffaele Brustia, Markus Peck-Radosavljevic, Giuseppe De Sario, Concepción Gómez-Gavara, Flair Jose Carrilho, Giulia Tesini, Priya Nair, Elide Gutierrez, Barbara M Zonderhuis, Bas Groot Koerkamp, Alejandro Forner, Trine Folseraas, Benjamin Goeppert, Keechilat Pavithran, Luis Bujanda, Joris I Erdmann, Juan W Valle, Jesus M Banales
{"title":"Chronic liver disease is associated with earlier-stage cholangiocarcinoma diagnosis and improved prognosis: Findings from the GLOBAL-BTC registry.","authors":"Laura Izquierdo-Sanchez, Jone Narbaiza, Julen Martin-Robles, Angela Lamarca, Heinz-Josef Klümpen, Adelaida La Casta, Arun Valsan, Stephanie Roessler, Chiara Braconi, Leonardo G da Fonseca, Cristina Dopazo, August T Juliebø, Ezequiel Mauro, Stefan Buettner, Domingo Balderramo, Mariano Ponz-Sarvise, Javier Díaz Ferrer, Krzysztof Zieniewicz, Kirsten Utpatel, Zeno Sparchez, Raffaele Brustia, Markus Peck-Radosavljevic, Giuseppe De Sario, Concepción Gómez-Gavara, Flair Jose Carrilho, Giulia Tesini, Priya Nair, Elide Gutierrez, Barbara M Zonderhuis, Bas Groot Koerkamp, Alejandro Forner, Trine Folseraas, Benjamin Goeppert, Keechilat Pavithran, Luis Bujanda, Joris I Erdmann, Juan W Valle, Jesus M Banales","doi":"10.1016/j.jhep.2026.08.020","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.08.020","url":null,"abstract":"<p><strong>Background and aims: </strong>Cholangiocarcinoma (CCA) is an aggressive cancer with rising incidence and mortality worldwide. Chronic liver disease (CLD) is a well-recognized risk factor, but its influence on tumor presentation and clinical outcomes remains unclear. We aimed to compare the clinical course of CCA in patients with and without CLD.</p><p><strong>Methods: </strong>We retrospectively analyzed 3,743 patients diagnosed with CCA between 2010 and 2024 across international centers. CLD was defined by documented primary sclerosing cholangitis, cirrhosis, viral hepatitis, or other chronic liver disorders; remaining patients were classified as non-CLD. Demographic, clinical, biochemical, treatment, and survival features were compared.</p><p><strong>Results: </strong>Among the CCA cohort, 993 patients had CLD. Compared with non-CLD patients (n=2,750), those with CLD were more frequently male (67% vs. 53%) and younger (median age 63 vs. 66 years). CLD-CCA patients more often presented with intrahepatic tumors (64% vs. 42%), better performance status (ECOG 0: 53% vs. 35%), lower CA19.9 levels (56 vs. 135 U/mL), and earlier-stage disease (localized: 57% vs. 43%; metastatic: 23% vs. 31%). In propensity score-matched analyses, patients with prior CLD were diagnosed at earlier CCA stages than non-CLD controls. Consequently, curative-intent tumor surgery was performed more frequently in CLD patients (60% vs. 48%), resulting into longer median overall survival (mOS 12.2 vs. 11.1 months; HR 0.88, 95%CI 0.80-0.98) and higher 5-year survival (OR 1.70, 95%CI 1.37-2.11), particularly in intrahepatic CCA (mOS: 14.2 vs. 11.1 months; HR 0.77, 95%CI 0.68-0.87; 5-year survival OR 2.19, 95%CI 1.60-3.01). Treatment responses across modalities were comparable between groups.</p><p><strong>Conclusion: </strong>Pre-existing CLD is associated with earlier-stage CCA diagnosis and improved survival, supporting the implementation of structured surveillance strategies in high-risk CLD populations.</p><p><strong>Impact and implications: </strong>This international multicenter study show that pre-existing CLD is associated with earlier-stage CCA diagnosis, likely due to closer clinical surveillance, greater eligibility for curative-intent surgery, and improved survival. Treatment responses were similar regardless of CLD status. These findings support established surveillance in high-risk groups and highlight the need to optimize strategies for selected moderate-to-high risk CLD populations, alongside prospective evaluation of their clinical utility, cost-effectiveness, and potential refinement through more accurate non-invasive biomarkers.</p>","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":40.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813077","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: \"Rifaximin and the DCA-serotonin axis in cirrhotic portal hypertension: how much of the benefit is bile-acid specific?\"","authors":"Ke-Qi Wang, Wei-Fen Xie","doi":"10.1016/j.jhep.2026.08.015","DOIUrl":"10.1016/j.jhep.2026.08.015","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":40.1,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793974","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":"Challenges and limitations of HbA1c in studies of advanced liver disease.","authors":"Tulio L Correa, Frederico G S Toledo","doi":"10.1016/j.jhep.2026.08.011","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.08.011","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":40.1,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793995","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 “Before repurposing Fusobacterium nucleatum in alcohol-associated liver disease: it is a rare, non-resident organism in the human alcoholic gut”","authors":"Long Xu, Hua Wang","doi":"10.1016/j.jhep.2026.07.031","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.07.031","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"24 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754709","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":"Internal Inconsistencies in the Training-Cohort Performance Table for the ELM Score","authors":"Nobuyuki Toshikuni","doi":"10.1016/j.jhep.2026.08.008","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.08.008","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"20 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754714","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":"Statistical pitfalls in interpreting zero HCC risk and HBsAg clearance in the long-term PAGE-B cohort.","authors":"Han Xiao, Gang Luo, Shaomin Xiong","doi":"10.1016/j.jhep.2026.07.033","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.07.033","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":40.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758300","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":"Statistical pitfalls in interpreting zero HCC risk and HBsAg clearance in the long-term PAGE-B cohort","authors":"Han Xiao, Gang Luo, Shaomin Xiong","doi":"10.1016/j.jhep.2026.07.033","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.07.033","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"16 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754718","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":"Can the CIRI model reliably predict cACLD decompensation for clinical adoption?","authors":"Junyuan Zhu, Chunqing Zhang","doi":"10.1016/j.jhep.2026.08.006","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.08.006","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":"36 1","pages":""},"PeriodicalIF":25.7,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148715536","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":"From definitions to phenotyping: a response to the illusion of harmonisation.","authors":"Florent Artru, Thierry Gustot, Nadim Mahmud","doi":"10.1016/j.jhep.2026.08.009","DOIUrl":"https://doi.org/10.1016/j.jhep.2026.08.009","url":null,"abstract":"","PeriodicalId":15888,"journal":{"name":"Journal of Hepatology","volume":" ","pages":""},"PeriodicalIF":40.1,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764801","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}