Interaction between cigarette smoking and hepatitis B and C virus infection on the risk of liver cancer: a meta-analysis.

INTRODUCTION Chronic infection with hepatitis B (HBV) and C viruses (HCV) as well as cigarette smoking are established risk factors of hepatocellular carcinoma (HCC), but it is unclear whether an interaction exists between these factors in causing hepatocellular carcinogenesis. We conducted a meta-analysis to evaluate the interaction of HBV and HCV infection and cigarette smoking on the risk of HCC. METHODS We systematically searched the PUBMED and the China National Knowledge Infrastructure databases. A total of 16 eligible publications were identified. Cigarette smoking and chronic HBV and HCV infections were dichotomized into present or absent. Additive (S) and multiplicative interaction indexes (V) between smoking and each of the two infections and their 95% confidence intervals (95% CI) were calculated for each study and then combined in a meta-analysis. RESULTS We found a more than additive interaction between HBV infection and cigarette smoking (S=1.44; 95% CI, 1.00-2.06; nine studies) and a more than multiplicative interaction (V=1.60; 95% CI, 1.16-2.20; six studies) between HCV infection and cigarette smoking. No publication bias was detected. CONCLUSION Smoking seems to interact with both HBV and HCV in determining HCC risk. A pooled analysis of individual subject data, with appropriate adjustment with other risk factors, is warranted to confirm these results. IMPACT The results of this study imply the evidence of a synergistic effect between smoking and HBV or HCV infection on the risk of HCC. Thus, chronic carriers of HBV or HCV are recommended to avoid smoking.