Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan.
OBJECTIVE
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.
Chen
Chi-Ling
CL
Graduate Institute of Clinical Medicine, College of Medicine, College of Public Health, National Taiwan University, Taipei.
Yang
Hwai-I
HI
Yang
Wei-Shiung
WS
Liu
Chun-Jen
CJ
Chen
Pei-Jer
PJ
You
San-Lin
SL
Wang
Li-Yu
LY
Sun
Chien-An
CA
Lu
Sheng-Nan
SN
Chen
Ding-Shin
DS
Chen
Chien-Jen
CJ
D000328:Adult; D002243:Carbolines; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000378:metabolism / Q000821:virology*; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D019694:Hepatitis B, Chronic / Q000453:epidemiology* / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000453:epidemiology* / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000378:metabolism; D008049:Lipase / Q000097:blood; D008113:Liver Neoplasms / Q000453:epidemiology* / Q000378:metabolism / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000453:epidemiology / Q000378:metabolism; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
D002243:Carbolines; D008049:Lipase; C025079:diazoline