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

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


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 (>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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Biomarkers / blood
  • DNA, Viral / blood
  • Female
  • Follow-Up Studies
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / diagnosis*
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / epidemiology*
  • Hepatitis C Antibodies / blood
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Population Surveillance
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Serologic Tests
  • Sex Factors
  • Taiwan / epidemiology
  • Time Factors
  • Viral Load


  • Biomarkers
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Hepatitis C Antibodies