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Volume 135, Issue 1 , Pages 111-121, July 2008

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

Chi–Ling Chen
- Graduate Institute of Clinical Medicine, College of Medicine, College of Public Health, National Taiwan University, Taipei
Hwai–I. Yang
- Genomics Research Center, Academia Sinica, Taipei
Wei–Shiung Yang
- Graduate Institute of Clinical Medicine, College of Medicine, College of Public Health, National Taiwan University, Taipei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei
Chun–Jen Liu
- Graduate Institute of Clinical Medicine, College of Medicine, College of Public Health, National Taiwan University, Taipei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei
- Hepatitis Research Center, National Taiwan University Hospital, Taipei
Pei–Jer Chen
- Graduate Institute of Clinical Medicine, College of Medicine, College of Public Health, National Taiwan University, Taipei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei
- Hepatitis Research Center, National Taiwan University Hospital, Taipei
San–Lin You
- Genomics Research Center, Academia Sinica, Taipei
Li–Yu Wang
- Department of Public Health, Tzu-Chi University, Hualien
Chien–An Sun
- School of Public Health, National Defense Medical Center, Taipei
Sheng–Nan Lu
- Department of Gastroenterology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan
Ding–Shin Chen
- Graduate Institute of Clinical Medicine, College of Medicine, College of Public Health, National Taiwan University, Taipei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei
- Hepatitis Research Center, National Taiwan University Hospital, Taipei
Chien–Jen Chen
- Genomics Research Center, Academia Sinica, Taipei
- Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei
- Address requests for reprints to: Chien-Jen Chen, ScD, Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan.

Received 11 January 2008; accepted 27 March 2008. published online 07 April 2008.

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.