Effects of Diabetes and Glycemic Control on Risk of Hepatocellular Carcinoma After Seroclearance of Hepatitis B Surface Antigen

Background & aims: Diabetes is associated with a 2-fold increase in risk of hepatocellular carcinoma (HCC) among patients with chronic hepatitis B virus (HBV) infection. However, we know little about the effect of diabetes on HCC risk after seroclearance of hepatitis B surface antigen (HBsAg). We evaluated the effect of diabetes and glycemic control on HCC development after HBsAg seroclearance in a population-wide study in Hong Kong.

Methods: We performed a retrospective study of 4568 patients with chronic HBV infection who cleared HBsAg from January 2000 through August 2016, using the Clinical Data Analysis and Reporting System of the Hospital Authority, Hong Kong. We collected and analyzed data on patient demographics, comorbidities, medications, laboratory test results, and subsequent development of HCC. The presence of diabetes was defined by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code, with level of hemoglobin A1c (HbA1c) above 6.5%, fasting glucose level of 7 mmol/L or more, or treatment with any antidiabetic agent.

Results: We identified 1560 patients with diabetes; 29 patients (1.9%) developed HCC after a median follow-up time of 3.4 years (interquartile range, 1.5-5.0 years). Diabetes was associated with increased risk of HCC after adjustment of age, sex, presence of cirrhosis, and the use of medications (adjusted hazard ratio, 1.85; 95% CI, 1.04-3.28; P = .036). Among patients with diabetes, time-weighted average level of HbA1c was an independent risk factor for HCC, after adjustment for age at clearance, use of statins, and other important covariates (adjusted hazard ratio: 1.51; 95% CI, 1.20-1.91; P < .001). A time-weighted average level of HbA1c of 7% or more was associated with a higher 5-year cumulative incidence of HCC (4.0%) than a time-weighted average HbA1c level below 7% (1.8%; log-rank test P = .035).

Conclusions: In a population-based analysis of patients with chronic HBV infection in Hong Kong, we found diabetes to be an independent risk factor for HCC after HBsAg seroclearance. However, glycemia control appears to reduce the risk of HCC.