Chronic liver disease is associated with earlier-stage cholangiocarcinoma diagnosis and improved prognosis: Findings from the GLOBAL-BTC registry
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND & AIMS: 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. METHODS: 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; patients without CLD were classified as non-CLD. Demographic, clinical, biochemical, treatment, and survival features were compared. RESULTS: 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 (65% vs. 43%), better performance status (ECOG 0: 53% vs. 35%), lower CA19.9 levels (56 vs. 135 U/ml), and earlier-stage disease (localized: 57% vs. 48%; 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 patients with CLD (58% vs. 45%), resulting in 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. CONCLUSION: 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. IMPACT AND IMPLICATIONS: This international multicenter study shows that pre-existing chronic liver disease (CLD) is associated with earlier-stage cholangiocarcinoma 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.
Source: Journal of Hepatology
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
Institutions: University of the Basque Country, Instituto de Salud Carlos III, Biogipuzkoa Health Research Institute, Donostiako Unibertsitate Ospitalea, University of Manchester, University Medical Center Groningen, University of Groningen, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Heidelberg University, University Hospital Heidelberg, Royal Marsden NHS Foundation Trust, Beatson West of Scotland Cancer Centre, Royal Marsden Hospital, University of Glasgow, Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Universitat Autònoma de Barcelona, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Oslo University Hospital, University of Oslo, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Erasmus MC, Erasmus MC Cancer Institute, Hospital Privado, Instituto Universitario de Ciencias Biomédicas de Córdoba, Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada, Universidad de Navarra, Universidad de San Martín de Porres, EsSALUD, Hospital Nacional Edgardo Rebagliati Martins, Medical University of Warsaw, University of Regensburg, Iuliu Hațieganu University of Medicine and Pharmacy, Inserm, Université Paris-Est Créteil, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Henri-Mondor, Klinikum Klagenfurt, Sapienza University of Rome, Humanitas University, Amsterdam University Medical Centers, Cancer Center Amsterdam, University of Amsterdam, University of Bern, Cholangiocarcinoma Foundation, Ikerbasque
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,500
Funders: Asociación Española para el Estudio del Hígado, PSC Partners Seeking a Cure, Taiho Pharmaceutical, Jazz Pharmaceuticals, Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza, Incyte, European Commission, Deutsche Forschungsgemeinschaft, Fundación Científica Asociación Española Contra el Cáncer, European Association for the Study of the Liver, Osasun Saila, Eusko Jaurlaritzako, Diputación Foral de Gipuzkoa, Instituto de Salud Carlos III
OpenAlex ID: W7204124759