Background: The risk of type 2 diabetes on the development of hepatocellular carcinoma remains inconclusive in different hepatitis statuses.
Methods: We prospectively followed a community-based cohort with 5,929 persons in southern Taiwan from January 1997 through December 2004, made up of 4,117 seronegative, 982 anti-hepatitis C virus-positive [HCV(+)], 696 hepatitis B surface antigen-positive [HBsAg(+)], and 134 coinfected persons. Before the study, 546 participants had developed diabetes. Hepatocellular carcinoma diagnoses were from the National Cancer Registry.
Results: After 50,899 person-years of follow-up, 111 individuals had developed hepatocellular carcinoma. The highest risk of hepatocellular carcinoma, compared with seronegative individuals without diabetes, was in anti-HCV(+) individuals with diabetes [incidence rate ratio (IRR), 76.0], then coinfected (IRR, 46.0), anti-HCV(+) without diabetes (IRR, 26.1), HBsAg(+) with diabetes (IRR, 21.4), and seronegative with diabetes (IRR, 7.2; P < 0.001). Anti-HCV(+) (n = 132) and seronegative individuals (n = 352) with diabetes had a higher cumulative incidence rate of hepatocellular carcinoma than those without diabetes (log-rank test, P < 0.001). Multivariate Cox proportional hazards analysis showed that gender, age, body mass index > or =30, HBsAg(+) [hazards ratio (HR), 12.6], anti-HCV(+) (HR, 18.8), coinfection (HR, 25.9), and diabetes [HR, 2.7; 95% confidence interval (95% CI), 1.7-4.3] were independent predictors of hepatocellular carcinoma (P < 0.05). After stratifying hepatitis status in multivariate Cox analysis, diabetes was significant for seronegative (HR, 5.4; 95% CI, 1.7-17.1) and anti-HCV(+) individuals (HR, 3.1; 95% CI, 1.7-5.4). Body mass index > or =30 was significant for HBsAg(+) individuals (HR, 3.3; 95% CI, 1.3-8.1).
Conclusion: Type 2 diabetes is a strong independent predictor of hepatocellular carcinoma in anti-HCV(+) and seronegative individuals but not in HBsAg(+) individuals.