Diabetes, hepatocellular carcinoma, and mortality in hepatitis C‐infected patients: A population‐based cohort study

Ting‐Shuo Huang, Chih‐Lang Lin, Mu‐Jie Lu, Chau‐Ting Yeh, Kung‐Hao Liang, Chi‐Chin Sun, Yu‐Chiau Shyu, Rong‐Nan Chien

The effect of diabetes mellitus (DM) on the development of hepatocellular carcinoma (HCC) and all-cause mortality after HCC development in chronic hepatitis C virus (HCV) infected patients remains inconclusive. This cohort study aimed to investigate these issues using the Taiwanese National Health Insurance Research Database. We retrieved and enrolled newly diagnosed DM patients with HCV from the Longitudinal Cohort of Diabetes Patients database. Propensity score matching-including age, sex, alcohol-related liver disease, and baseline liver cirrhosis-was used to identify and enroll HCV patients without DM from the Longitudinal Health Insurance Database (n = 1,686). A multi-state model was used to investigate transitions from "start-to-HCC", "start-to-death", and "HCC-to-death". The multi-state model showed higher cumulative hazards for "start-to-HCC", "start-to-death", and "HCC-to-death" transitions in the DM (vs. non-DM) cohort. The cumulative probability of death with or without HCC after 10 years of follow-up was higher in the DM cohort than in the non-DM cohort. Multivariable transition-specific Cox models demonstrated that DM significantly increased the risk for transition from "start-to-HCC" (adjusted hazard ratio [aHR] 1.36; 95% confidence interval [CI] 1.16-1.59; P < 0.001), "start-to-death" (aHR 2.61; 95% CI: 2.05-3.33; P < 0.001), and "HCC-to-death" (aHR 1.36; 95% CI 1.10-1.68; P = 0.005). The effect of liver cirrhosis on "start-to-HCC" and "start-to-death" transitions decreased over time, particularly within 2 years. DM increased the risk of HCC development in HCV-infected patients and the risk of all-cause mortality in patients with or without HCC.