Gastroenterology
Volume 139, Issue 2 , Pages 474-482, August 2010

Incidence and Determinants of Spontaneous Hepatitis B Surface Antigen Seroclearance: A Community-Based Follow-Up Study

  • Jessica Liu

      Affiliations

    • Rollins School of Public Health, Emory University, Atlanta, Georgia
    • Genomics Research Center, Academia Sinica, Taipei, Taiwan
    • ,
  • Hwai–I. Yang

      Affiliations

    • Genomics Research Center, Academia Sinica, Taipei, Taiwan
    • ,
  • Mei–Hsuan Lee

      Affiliations

    • Genomics Research Center, Academia Sinica, Taipei, Taiwan
    • Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan
    • ,
  • Sheng–Nan Lu

      Affiliations

    • Department of Gastroenterology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan
    • ,
  • Chin–Lan Jen

      Affiliations

    • Genomics Research Center, Academia Sinica, Taipei, Taiwan
    • ,
  • Li–Yu Wang

      Affiliations

    • MacKay Medical College, Taipei, Taiwan
    • ,
  • San–Lin You

      Affiliations

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

      Affiliations

    • Research and Development, Bristol-Myers Squibb Company, Wallingford, Connecticut
    • ,
  • Chien–Jen Chen

      Affiliations

    • Genomics Research Center, Academia Sinica, Taipei, Taiwan
    • Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, 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 115, Taiwan. fax: (886) 2-2787-8784
    • ,
  • REVEAL-HBV Study Group

Received 7 January 2010; accepted 12 April 2010. published online 30 April 2010.

Background & Aims

Seroclearance of hepatitis B surface antigen (HBsAg) is one of the most important clinical outcomes for chronic hepatitis B treatment trials. Few studies have explored the incidence and determinants of spontaneous seroclearance using a long-term follow-up study. This study aimed to examine the natural history and predictors of HBsAg seroclearance.

Methods

A total of 3087 individuals with chronic hepatitis B virus infection were enrolled between 1991 and 1992 in this community-based study. Serum samples collected at baseline and follow-up examinations were tested for HBsAg, hepatitis B e antigen (HBeAg), serum hepatitis B virus (HBV)-DNA levels, and anti–hepatitis C virus serostatus. Cox proportional hazards models were used to estimate HBsAg seroclearance rate ratios associated with various determinants.

Results

HBsAg seroclearance occurred in 562 participants during 24,829 person-years of follow-up evaluation, giving a 2.26% annual seroclearance rate. HBV-DNA levels at baseline and follow-up evaluation were the most significant predictor of seroclearance. Higher HBV viral loads conferred lower HBsAg seroclearance rates (P < .001). A spontaneous decrease in follow-up HBV-DNA level (≥3 log) was associated significantly with seroclearance, showing an adjusted odds ratio of 4.17 (95% confidence interval, 2.55–6.82). Among those with seroclearance, 95.8% had undetectable HBV-DNA levels before seroclearance. Cumulative incidence of HBsAg seroclearance at 60 and 100 months after serum HBV-DNA level decreased to undetectable was 25.8% and 51.3%, respectively.

Conclusions

This study reveals determinants of HBsAg seroclearance, and suggests that a low viral load is an important factor affecting the natural seroclearance of HBsAg, indicating significant clinical implications for the treatment of chronic HBV.

Keywords: Spontaneous HBsAg Seroclearance, Incidence, Determinants

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, REVEAL-HBV, Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus

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 Conflicts of interest These authors disclose the following: Dr Iloeje is an employee of and holds stock in Bristol-Myers Squibb Company. The remaining authors disclose no conflicts.

 Funding This study was supported by research grants from the Department of Health, Executive Yuan, Taipei, Taiwan; Academia Sinica, Taipei, Taiwan; National Health Research Institutes, Chunan, Taiwan; and the Bristol-Myers Squibb Company, Wallingford, CT, to conduct the laboratory tests for this study.The funding sources of this study had no role in the design or conduct of the study, nor did they have any role in the collection, management, analysis, and interpretation of the data as well as the preparation, review, or approval of the manuscript. All data handling and statistical analyses were performed by staff at the National Taiwan University and Academia Sinica. At no time did the funding sources have access to the data.

PII: S0016-5085(10)00656-6

doi:10.1053/j.gastro.2010.04.048

Gastroenterology
Volume 139, Issue 2 , Pages 474-482, August 2010

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