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

BACKGROUND AND 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; remaining patients 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 (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. 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 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.