title: Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance: a community-based follow-up study.
abstract: OBJECTIVE
  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.
authors.affiliation: Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Liu
authors.forename: Hwai-I
authors.initials: HI
authors.lastname: Yang
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Lee
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
authors.forename: Chin-Lan
authors.initials: CL
authors.lastname: Jen
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Wang
authors.forename: San-Lin
authors.initials: SL
authors.lastname: You
authors.forename: Uchenna H
authors.initials: UH
authors.lastname: Iloeje
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology*; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012698:Serologic Tests; D012737:Sex Factors; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors; D019562:Viral Load
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D018937:Hepatitis C Antibodies