Hepatitis B Virus Infection and Hepatocellular Carcinoma Among Parous Taiwanese Women: Nationwide Cohort Study

Few long-term studies of hepatitis B virus (HBV) infection and hepatocellular carcinoma have focused on women. We used a nationwide cohort of reproductive-aged Taiwanese women to study relationships of HBV infection and parity with hepatocellular carcinoma risk. Prenatal test results were available for hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) in the National Hepatitis B Vaccination Registry from 1 782 401 pregnant women tested from October 1, 1983, through March 31, 2000. Data from the 306 women who were diagnosed with hepatocellular carcinoma were ascertained during 15 901 722 person-years of follow-up through linkage with National Cancer Registry and National Death Certification Registry. We used Cox proportional hazards models to investigate the association of age and reproductive and serological parameters with the risk of hepatocellular carcinoma. Incidence rates for hepatocellular carcinoma were 0.55, 7.91, and 8.76 per 100 000 person-years among women who were HBsAg negative (ie, noncarriers), HBsAg positive plus HBeAg negative, and HBsAg positive plus HBeAg positive, respectively (compared with noncarriers, for HBsAg-positive and HBeAg-positive women, age-adjusted hazard ratio [HR] for developing hepatocellular carcinoma = 17.31, 95% confidence interval [CI] = 12.08 to 24.81; and for HBsAg-negative plus HBeAg-positive women, HR = 13.94, 95% CI = 10.34 to 18.79). Incidence rates were 0.39, 3.10, and 9.01 per 100 000 person-years, respectively, among persistent noncarriers, HBsAg-serocleared carriers, and persistent HBsAg carriers (compared with noncarriers, for HBsAg-serocleared carriers, age-adjusted HR = 7.95, 95% CI = 3.50 to 18.04; and for HBsAg persistence, HR = 23.13, 95% CI = 14.23 to 37.61). Incidence rates were 2.04, 1.55, and 1.66 per 100 000 person-years for women who had one, two, or three or more children, respectively (compared with one child, for two children, age- and HBsAg-adjusted HR = 0.68, 95% CI = 0.50 to 0.93; and for three or more children, HR = 0.63, 95% CI = 0.42 to 0.92). The risk for hepatocellular carcinoma was statistically significantly higher among women with chronic or active HBV infections and among those with persistent HBV infection or who underwent HBsAg seroclearance during follow-up than among HBV-unexposed women. This risk decreased as parity increased, independent of HBsAg status and age.