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Gastroenterology. 2010 Aug;139(2):474-82. doi: 10.1053/j.gastro.2010.04.048. Epub 2010 Apr 29.

Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance: a community-based follow-up study.

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  • 1Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.



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.


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.


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 (>or=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.


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.

Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

[PubMed - indexed for MEDLINE]
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