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

Background and aim: 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.

Methods: 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 = 1686). A multi-state model was used to investigate transitions from "start-to-HCC," "start-to-death," and "HCC-to-death."

Results: 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.

Conclusions: Diabetes mellitus increased the risk of HCC development in HCV-infected patients and the risk of all-cause mortality in patients with or without HCC.