Association between non-alcoholic fatty liver disease and the risk of biliary tract cancers: A South Korean nationwide cohort study

Aims: The association between non-alcoholic fatty liver disease (NAFLD) and cholangiocarcinoma has been previously reported only in case–control studies. Therefore, we conducted this nationwide cohort study to evaluate the longitudinal association between NAFLD and the risk of biliary tract cancer (BTC), including cholangiocarcinoma and gallbladder cancer. Methods: We included 8,120,674 adults who underwent national health screening in 2009 based on the Korean National Health Insurance Service data. NAFLD was determined using the fatty liver index: ≥60, NAFLD; 30–59, intermediate score; <30, no NAFLD. The exclusion criteria were baseline clinical liver disease, heavy alcohol consumption and cancer. Participants were followed up until December 2017 for the development of BTC. Cox proportional hazards regression models were performed. Results: During the median follow-up period of 7.2 years, 13,043 patients were with newly diagnosed BTC. NAFLD was associated with an increased risk of BTC (adjusted hazard ratio [aHR], 1.28; 95% CI, 1.20–1.37) compared with no NAFLD. The aHRs for the association of cholangiocarcinoma and gallbladder cancer with NAFLD were 1.33 (95% CI, 1.23–1.43) and 1.14 (95% CI, 1.003–1.29), respectively. Overall, the aHR for BTC tended to increase with the increasing fatty liver index (P for trend < 0.001). Concomitant NAFLD and diabetes were associated with an increased risk of BTC by 47% (aHR, 1.47; 95% CI, 1.35–1.60). Conclusion: In this nationwide cohort study, NAFLD was associated with an increased risk of cholangiocarcinoma and gallbladder cancer. This finding suggests that NAFLD is a potentially modifiable risk factor for BTC.