Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan

Gastroenterology. 2008 Jul;135(1):111-21. doi: 10.1053/j.gastro.2008.03.073. Epub 2008 Apr 4.


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 (RR(a)) and 95% confidence interval (95% CI) were estimated using Cox proportional hazards models.

Results: Extreme obesity (body mass index >or=30 kg/m(2)) was independently associated with a 4-fold risk of HCC (RR(a), 4.13; 95% CI, 1.38-12.4) among anti-HCV-seropositive subjects and a 2-fold risk (RR(a), 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 (RR(a), 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 (RR(a), 3.52; 95% CI, 1.29-9.24) and lowest in HBV carriers (RR(a), 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carbolines
  • Carcinoma, Hepatocellular / epidemiology*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / virology*
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / metabolism
  • Female
  • Follow-Up Studies
  • Hepatitis B, Chronic / epidemiology*
  • Hepatitis B, Chronic / metabolism
  • Hepatitis C, Chronic / epidemiology*
  • Hepatitis C, Chronic / metabolism
  • Humans
  • Hypertension / epidemiology
  • Hypertension / metabolism
  • Lipase / blood
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Obesity / epidemiology
  • Obesity / metabolism
  • Risk Factors
  • Taiwan / epidemiology


  • Carbolines
  • Lipase
  • diazoline