Gastroenterology
Volume 138, Issue 5 , Pages 1747-1754.e1, May 2010

Carriers of Inactive Hepatitis B Virus Are Still at Risk for Hepatocellular Carcinoma and Liver-Related Death

  • Jin–De Chen

      Affiliations

    • Department of Internal Medicine, Bei-Hu Branch, National Taiwan University Hospital, Taipei, Taiwan
    • Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan
    • ,
  • Hwai–I. Yang

      Affiliations

    • Genomics Research Center, Academia Sinica, Taipei, Taiwan
    • ,
  • Uchenna H. Iloeje

      Affiliations

    • Research and Development, Bristol-Myers Squibb Co., Wallingford, Connecticut
    • ,
  • San–Lin You

      Affiliations

    • Genomics Research Center, Academia Sinica, Taipei, Taiwan
    • ,
  • Sheng–Nan Lu

      Affiliations

    • Department of Gastroenterology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan
    • ,
  • Li–Yu Wang

      Affiliations

    • Department of Medicine, Mackay Medical College, Taipei County, Taiwan
    • ,
  • Jun Su

      Affiliations

    • Research and Development, Bristol-Myers Squibb Co., Wallingford, Connecticut
    • ,
  • Chien–An Sun

      Affiliations

    • Department of Public Health, College of Medicine, Fu-Jen Catholic University, Taipei County, Taiwan
    • ,
  • Yun–Fan Liaw

      Affiliations

    • Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung University, Taipei, Taiwan
    • ,
  • Chien–Jen Chen

      Affiliations

    • Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan
    • Genomics Research Center, Academia Sinica, Taipei, Taiwan
    • Corresponding Author InformationReprint requests Address requests for reprints to: Chien-Jen Chen, ScD, Genomics Research Center, Academia Sinica, 128 Academia Road Section 2, Nankang, Taipei 11529, Taiwan
    • ,
  • Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer in HBV (REVEAL-HBV) Study Group

      Affiliations

    • Other Members of the REVEAL-HBV Study Group are listed in the Acknowledgments

Received 28 October 2009; accepted 20 January 2010. published online 29 January 2010.

Background & Aims

The risk and the predictors of liver disease progression in carriers of inactive hepatitis B virus (HBV) are unclear.

Methods

Participants in the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) study who were seronegative for hepatitis B e antigen; had serum levels of HBV DNA <10,000 copies/mL; and did not have cirrhosis, hepatocellular carcinoma, or increased serum levels of alanine aminotransferase were classified as carriers of inactive HBV (n = 1932). Study participants who were seronegative for HB surface antigen and antibodies against hepatitis C virus, yet had similar clinical liver features, were the controls (n = 18,137). Liver-related death and new cases of hepatocellular carcinoma were ascertained through computerized data linkage with National Cancer Registry and Death Certification profiles. The disease progression rates were estimated. The multivariate-adjusted hazard ratios for risk predictors were derived from Cox regression models.

Results

There were 20,069 participants, contributing a total of 262,122 person-years, with a mean follow-up of 13.1 years. Annual incidence rates of hepatocellular carcinoma and liver-related death were 0.06% and 0.04%, respectively, for inactive HBV carriers; rates were 0.02%, and 0.02% for controls, respectively. The multivariate-adjusted hazard ratios for carriers of inactive HBV, compared to controls, were 4.6 (95% confidence interval: 2.5–8.3) for hepatocellular carcinoma and 2.1 (95% confidence interval: 1.1–4.1) for liver-related death. Older age and alcohol drinking habits were independent predictors of risk for carriers of inactive HBV to develop hepatocellular carcinoma.

Conclusions

Carriers of inactive HBV have a substantial risk of hepatocellular carcinoma and liver-related death compared with individuals not infected with HBV.

Keywords: Inactive HBV Carrier, Hepatocellular Carcinoma, Liver-Related Death

Abbreviations used in this paper: ALT, alanine aminotransferase, CI, confidence interval, HBeAg, hepatitis B e antigen, HBsAg, hepatitis B surface antigen, HBV, hepatitis B virus, HCV, hepatitis C virus, HRa, multivariate-adjusted hazard ratio, REVEAL-HBV, Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus

 

 Conflicts of interest The authors disclose no conflicts.

 Funding Funding was received from Bristol-Myers Squibb Company (for conducting part of laboratory tests), Department of Health, Executive Yuan, National Health Research Institutes, and Academia Sinica in Taiwan. None of the funding organizations played a role in the design and conduct of this study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript.

PII: S0016-5085(10)00148-4

doi:10.1053/j.gastro.2010.01.042

Gastroenterology
Volume 138, Issue 5 , Pages 1747-1754.e1, May 2010