Journal of the National Cancer Institute Advance Access published online on June 17, 2009
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djp146
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© The Author 2009. Published by Oxford University Press.
ARTICLES |
Hepatitis B Virus Infection and Hepatocellular Carcinoma Among Parous Taiwanese Women: Nationwide Cohort Study
Affiliations of authors: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (C-WF, GDK, KEN, MF); Genomics Research Center, Academia Sinica, Taipei, Taiwan (Y-CC, S-LY, C-JC); Graduate Institute of Epidemiology, National Taiwan University, Taipei, Taiwan (Y-CC, S-LY, C-JC); Centers for Disease Control, Taipei, Taiwan (H-SK)
Correspondence to: Chien-Jen Chen, ScD, Genomics Research Center, Academia Sinica, 128 Academia Rd, Section 2, Nankang, Taipei 11529, Taiwan (e-mail: cjchen{at}ntu.edu.tw).
Background: 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.
Methods: 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.
Results: 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).
Conclusions: 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.
| CONTEXT AND CAVEATS Prior knowledge Women have been the subject of few long-term studies of the association between hepatitis B virus (HBV) infection and hepatocellular carcinoma. Study design Data from four registries in Taiwan provided information about pregnant women who were tested for hepatitis B surface antigen (HBsAg) and e antigen between 1983 and 2000 and subsequent diagnoses of hepatocellular carcinoma. Contribution Risk for hepatocellular carcinoma during follow-up was statistically significantly higher among pregnant women with chronic, active, or persistent HBV infections or who underwent HBsAg seroclearance, than among HBV-unexposed women. Risk decreased as parity increased, independent of HBsAg status and age. Implications Biological mechanisms of the association between parity and reduced risk of hepatocellular carcinoma merit further investigation. Limitations Some false-positive results cannot be excluded because confirmatory HBsAg testing (neutralization) was not done. Seroclearance could have been underestimated because testing frequency depended on the frequency of pregnancies and prenatal testing. The number of children included was limited to those born during the study period. From the Editors
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Manuscript received October 3, 2008; revised April 21, 2009; accepted April 30, 2009.
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J Natl Cancer Inst 2009 101: 969.
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