Gastroenterology

Gastroenterology

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

Clinical—Liver, Pancreas, and Biliary Tract
Incidence and Determinants of Spontaneous Hepatitis B Surface Antigen Seroclearance: A Community-Based Follow-Up Study

https://doi.org/10.1053/j.gastro.2010.04.048Get rights and content

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.

Section snippets

Study Cohort

From 1991 to 1992, all 89,293 inhabitants aged 30 to 65 years, who were residing in 7 townships (Sanchi, Chutung, Potzu, Kaoshu, Makung, Hushi, and Paisha) in Taiwan, were invited to participate in a cancer screening program as a part of the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) study.10, 27 Recruitment was performed by mailed letters, and follow-up telephone calls were made to those who did not respond to the initial

Study Cohort

Figure 1 shows the flow of study participants through the study. A total of 3087 participants with no previous history of treatment for HBV who were seropositive for HBsAg, anti-HCV seronegative, and free of cirrhosis at study entry were included in this analysis. Among the 3087 participants in this study, 65% were men, the median age was 45 years old, and most were HBeAg seronegative (84%), had ALT levels less than 45 U/L (94%), and had no previous history of diabetes at baseline (98%).

HBsAg Seroclearance Rates and Cumulative Probability of Seroclearance

There

Discussion

This was a large community-based sample of HBsAg carriers who were followed up. Previous studies of the determinants of HBsAg seroclearance have been either clinic-based, or have had smaller numbers of participants.21, 22, 24, 26 In this study, 562 of 3087 chronic HBV carriers spontaneously cleared HBsAg, showing a seroclearance rate of 2.26 per 100 person-years. This rate is substantially higher than previously reported rates of HBsAg seroclearance in high-endemic areas, which ranged from 0.5%

Acknowledgments

J.L. and H.-I.Y. contributed equally to this article.

Other members of the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) Study Group are as follows: National Taiwan University Hospital: C. Y. Hsieh, H. S. Lee, P. M. Yang, C. H. Chen, J. D. Chen, S. P. Huang, and C. F. Jan; National Taiwan University: T.H.H. Chen; National Defense Medical Center: C. A. Sun; Taipei City Psychiatric Center: M. H. Wu; Tzu Chi University: S. Y. Chen; Shin

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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.

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