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

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http://www.gastrojournal.org/article/PIIS0016508510006566/abstract?rss=yes

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

Liu

AffiliationsRollins School of Public Health, Emory University, Atlanta,

GeorgiaGenomics Research Center, Academia Sinica, Taipei, Taiwan

, Hwai–I. Yang

AffiliationsGenomics Research Center, Academia Sinica, Taipei, Taiwan

, Mei–Hsuan Lee

AffiliationsGenomics Research Center, Academia Sinica, Taipei, TaiwanGraduate

Institute of Epidemiology, College of Public Health, National Taiwan University,

Taipei, Taiwan

, Sheng–Nan Lu

AffiliationsDepartment of Gastroenterology, Kaohsiung Chang-Gung Memorial

Hospital, Kaohsiung, Taiwan

, Chin–Lan Jen

AffiliationsGenomics Research Center, Academia Sinica, Taipei, Taiwan

, Li–Yu Wang

AffiliationsMacKay Medical College, Taipei, Taiwan

, San–Lin You

AffiliationsGenomics Research Center, Academia Sinica, Taipei, Taiwan

, Uchenna H. Iloeje

AffiliationsResearch and Development, Bristol-Myers Squibb Company, Wallingford,

Connecticut

, Chien–Jen Chen

AffiliationsGenomics Research Center, Academia Sinica, Taipei, TaiwanGraduate

Institute of Epidemiology, College of Public Health, National Taiwan University,

Taipei, TaiwanReprint 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.

Abstract

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. 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.

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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

© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.