Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study

Choledocholithiasis has been reported to be associated with the occurrence of cholangiocarcinoma (CCA); however, the association has not yet been sufficiently demonstrated. This study aimed to evaluate the association between choledocholithiasis (common bile duct stones) and CCA.

This nationwide retrospective cohort study used the Health Insurance Review and Assessment database of individuals diagnosed with choledocholithiasis between 2008 and 2009 in South Korea. Individuals were stratified by age, and CCA was categorized into extrahepatic CCA (ECA) and intrahepatic CCA (ICA). The standardized incidence ratio (SIR) was calculated to compare CCA incidence between patients with choledocholithiasis and the general population.

The study enrolled 20,808 patients with choledocholithiasis (52.35% men and 47.65% women; male-to-female ratio: 1.09:1). Over a 10-year follow-up period, CCA occurred in 548 (2.64%) patients, comprising 238 (1.14%) ECA cases and 310 (1.48%) ICA cases. The SIR was 25.23 (95% confidence interval [CI]: 21.98-28.85) for ECA and 24.64 (95% CI: 21.87-27.73) for ICA. Statistical significance persisted even after excluding cases within the first 2 years from the index date, with an SIR of 18.63 (95% CI: 16.23-21.28) for ICA and 12.73 (95% CI: 10.50-15.30) for ECA. The SIRs peaked in patients diagnosed with choledocholithiasis at the age of 70-79 years (SIR 16.61, 95% CI: 11.83-22.69) for ECA and 60-69 years (SIR 29.27, 95% CI: 23.53-36.03) for ICA.

Our study demonstrated a significant association between choledocholithiasis and cholangiocarcinoma, particularly those in their 70s for ECA and 60s for ICA. However, causation cannot be established due to the retrospective design.