Sex-Modified Effect of Hepatitis B Virus Infection on Mortality From Primary Liver Cancer

Sex and hepatitis B virus (HBV) infection are both important risk factors for primary liver cancer. However, their possible biologic interaction has not been well studied. The authors examined data from 89,789 subjects aged 25–69 years who participated in a 14-year cohort study (1992–2006) conducted in Haimen, China. An age-stratified Cox proportional hazards model was used for multivariate analysis. The authors assessed the combined effect of sex and HBV infection on liver cancer mortality by calculating 3 interaction measures: the relative risk due to interaction, the attributable proportion of interaction, and the synergy index. There was a greater risk difference between hepatitis B surface antigen carriers and noncarriers among men than among women. After adjustment for potential confounders, the relative risk due to interaction, the attributable proportion of interaction, and the synergy index were 33.27 (95% confidence interval (CI): 22.54, 43.99), 0.59 (95% CI: 0.55, 0.63), and 2.49 (95% CI: 2.13, 2.90), respectively, suggesting a significant synergistic effect of the interaction between sex and HBV infection on liver cancer mortality. HBV infection had a larger impact on liver cancer mortality in men than in women, which may explain at least part of the sex difference in liver cancer risk.