Metabolic Factors and Risk of Hepatocellular Carcinoma by Chronic Hepatitis B/C Infection: A Follow-up Study in Taiwan

Background & Aims: This study investigated whether obesity, diabetes, and other metabolic factors are independently associated with hepatocellular carcinoma (HCC), stratified by hepatitis B virus (HBV) and hepatitis C virus (HCV) serostatus, and explored the possible joint influence of obesity/diabetes and HBV/HCV infections on the risk of HCC. Methods: A total of 23,820 residents in Taiwan were recruited and followed up for 14 years. All analyses were stratified by hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) at enrollment, and 218 subjects positive for both seromarkers were excluded. Incident HCC cases were identified via linkage to the national cancer registry. Multivariate-adjusted relative risk (RRa) and 95% confidence interval (95% CI) were estimated using Cox proportional hazards models. Results: Extreme obesity (body mass index ≥30 kg/m2) was independently associated with a 4-fold risk of HCC (RRa, 4.13; 95% CI, 1.38-12.4) among anti-HCV-seropositive subjects and a 2-fold risk (RRa, 2.36; 95% CI, 0.91-6.17) in persons without HBV and HCV infections, after controlling for other metabolic components, but not in HBsAg-seropositive subjects (RRa, 1.36; 95% CI, 0.64-2.89). Diabetes was associated with HCC in all 3 groups, with the highest risk in those with HCV infection (RRa, 3.52; 95% CI, 1.29-9.24) and lowest in HBV carriers (RRa, 2.27; 95% CI, 1.10-4.66). We found more than 100-fold increased risk in HBV or HCV carriers with both obesity and diabetes, indicating synergistic effects of metabolic factors and hepatitis. Conclusions: The finding that both obesity and diabetes are predictors of HCC risk, possibly differently depending on HBV and HCV infection status, may shed some light in preventing HCC.