Chronic liver disease is associated with earlier-stage cholangiocarcinoma diagnosis and improved prognosis: Findings from the GLOBAL-BTC registry.

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. 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. 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. 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. 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.