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.

References 

  1. Lee WM. Hepatitis B virus infection. N Engl J Med. 1997;337:1733–1745
  2. Hadziyannis SJ, Vassilopoulos D. Hepatitis B e antigen-negative chronic hepatitis B. Hepatology. 2001;34:617–624
  3. Lok AS, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000—summary of a workshop. Gastroenterology. 2001;120:1828–1853
  4. Pawlotsky JM. Molecular diagnosis of viral hepatitis. Gastroenterology. 2002;122:1554–1568
  5. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507–539
  6. Zacharakis GH, Koskinas J, Kotsiou S, et al. Natural history of chronic HBV infection: a cohort study with up to 12 years' follow-up in North Greece (part of the Interreg I-II/EC-project). J Med Virol. 2005;77:173–179
  7. Chu CM, Hung SJ, Lin J, et al. Natural history of hepatitis B e antigen to antibody seroconversion in patients with normal serum aminotransferase levels. Am J Med. 2004;116:829–834
  8. Chu CM, Liaw YF. Spontaneous relapse of hepatitis in inactive HBsAg carriers. Hep Intl. 2007;1:311–315
  9. Martinot-Peignoux M, Boyer N, Colombat M, et al. Serum hepatitis B virus DNA levels and liver histology in inactive HBsAg carriers. J Hepatol. 2002;36:543–546
  10. Gigi E, Lalla T, Orphanou E, et al. Long term follow-up of a large cohort of inactive HBsAg (+)/ HBeAg (−)/ anti-HBe (+) carriers in Greece. J Gastrointestin Liver Dis. 2007;16:19–22
  11. Chu CM, Liaw YF. Predictive factors for reactivation of hepatitis B following hepatitis B e antigen seroconversion in chronic hepatitis B. Gastroenterology. 2007;133:1458–1465
  12. Karmen A, Wroblewski F, Ladue JS. Transaminase activity in human blood. J Clin Invest. 1955;34:126–131
  13. Prati D, Taioli E, Zanella A, et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med. 2002;137:1–10
  14. Kaplan MM. Alanine aminotransferase levels: what's normal?. Ann Intern Med. 2002;137:49–51
  15. Roderick P. Liver function tests: defining what's normal. BMJ. 2004;328:987
  16. Iloeje UH, Yang HI, Jen CL, et al. Risk and predictors of mortality associated with chronic hepatitis B infection. Clin Gastroenterol Hepatol. 2007;5:921–931
  17. Kim HC, Nam CM, Jee SH, et al. Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study. BMJ. 2004;328:983
  18. Yuen MF, Yuan HJ, Wong DK, et al. Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications. Gut. 2005;54:1610–1614
  19. Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73
  20. Iloeje UH, Yang HI, Su J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130:678–686
  21. Chen CJ, Iloeje UH, Yang HI. Long-term outcomes in hepatitis B: the REVEAL-HBV study. Clin Liver Dis. 2007;11:797–816viii
  22. Peña EA, Rohatgi VK. Small sample and efficiency results for the Nelson-Aalen estimator. J Stat Plann Inference. 1993;37:193–202
  23. Breslow N, Crowley J. A large sample study of the life table and product limit estimates under random censorship. Ann Stat. 1974;2:437–453
  24. Aalen O. Nonparametric inference for a family of counting processes. Ann Stat. 1978;6:701–726
  25. Yang HI, Lu SN, Liaw YF, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002;347:168–174
  26. Tai DI, Lin SM, Sheen IS, et al. Long-term outcome of hepatitis B e antigen-negative hepatitis B surface antigen carriers in relation to changes of alanine aminotransferase levels over time. Hepatology. 2009;49:1859–1867

 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