Association between glycemic control and hepatocellular carcinoma risk in people with type 2 diabetes, stratified by chronic hepatitis B or C infection

Chronic viral hepatitis is a major risk factor for hepatocellular carcinoma (HCC). Though diabetes is another risk of HCC, it remains indeterminant as to whether glycemic burden in individuals with type 2 diabetes (T2D) should be differentially managed according to the presence of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV). To evaluate the association between glycemic burden and HCC risk in individuals with T2D, stratified by viral hepatitis status, including HBV and HCV. Retrospective cohort study. This study analyzed 30,055 individuals with T2D from the Chang Gung Research Database (2009-2016), stratified into non-HBV/non-HCV, HBV, and HCV groups. Glycemic burden was assessed using baseline glycated hemoglobin (HbA1c), high HbA1c variability, and optimal glycemic control, defined as maintaining HbA1c <7% for more than 80% of the follow-up period. Cox proportional hazard models were used to identify HCC risk factors. Over a mean follow-up of 6.4 years, 644 individuals (2.14%) developed HCC. Viral hepatitis was the predominant independent risk factor, followed by elevated fibrosis-4 (FIB-4) scores, male sex, older age, low albumin, and low platelet count. Neither baseline HbA1c nor high HbA1c variability was associated with HCC risk in the overall T2D population or stratified groups. However, optimal glycemic control was significantly associated with reduced HCC risk in individuals with HBV (adjusted hazard ratio (HR) = 0.671, 95% confidence interval (CI) = 0.465-0.969, p = 0.033) and demonstrated a potentially beneficial role in non-HBV/non-HCV patients with presumed metabolic dysfunction-associated fatty liver disease (presumed MAFLD; adjusted HR = 0.574, 95% CI: 0.309-1.065, p = 0.079). Optimal glycemic control may reduce HCC risk in individuals with T2D and HBV and potentially benefits those with presumed MAFLD, although its role in HCV-related HCC appears limited. These findings highlight the need for tailored glycemic management strategies based on viral hepatitis type.