title: Predictors of hepatitis B e antigen-negative hepatitis in chronic hepatitis B virus-infected patients from childhood to adulthood.
abstract: Hepatitis B e antigen (HBeAg)-negative hepatitis is a clinical indicator of poor outcome for chronic hepatitis B viral (HBV) infection. This long-term prospective cohort study aimed to elucidate the predictors of developing HBeAg-negative hepatitis in chronic HBV-infected subjects followed from childhood to adulthood. We followed 434 HBeAg-positive chronic HBV-infected patients from a median age of 7.22 years (interquartile range 4.31-10.21 years). Spontaneous HBeAg seroconversion occurred in 359 subjects at a median age of 13.93 years (interquartile range 8.76-20.59 years), and 75 subjects developed HBeAg seroconversion after antiviral therapy. These patients were followed for a median of 14.40 years (interquartile range 6.14-22.02 years) after HBeAg seroconversion. Clinical data were analyzed to delineate the predictors of developing HBeAg-negative hepatitis. The HBV basal core promoter and precore/core gene sequences were also evaluated in subjects with and without HBeAg-negative hepatitis. The overall annual incidence of HBeAg-negative hepatitis was 0.37% (95% confidence internal 0.35-0.39) in spontaneous HBeAg seroconverters. The overall annual incidence of HBeAg-negative hepatitis increased to 2.64% in lamivudine-treated subjects but did not increase in those treated with interferon-alpha (0.58%). Male gender (hazard ratio = 3.15), HBV genotype C (hazard ratio = 4.40), HBeAg seroconversion after 18 years of age (hazard ratio = 2.46), and lamivudine therapy prior to HBeAg seroconversion (hazard ratio = 1.42) were predictors of HBeAg-negative hepatitis in HBeAg seroconverters (P < 0.05). HBeAg-negative hepatitis subjects carried more A1762T/G1764A, C2063A, and A2131C HBV gene mutations than those without HBeAg-negative hepatitis.
  
  
  CONCLUSIONS
  HBeAg seroconversion during childhood predicts a lower risk of HBeAg-negative hepatitis in later life. Interferon-alpha therapy may be an effective antiviral therapy beneficial in chronic HBV-infected children with severe inflammation that facilitates HBeAg seroconversion in earlier life.
authors.affiliation: Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Jia-Feng
authors.initials: JF
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University, Taipei, Taiwan.|Department of Medical Education, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Chiu
authors.affiliation: Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University, Taipei, Taiwan.|Department of Emergency, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Kai-Chi
authors.initials: KC
authors.lastname: Chang
authors.affiliation: Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University, Taipei, Taiwan.|Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Huey-Ling
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University, Taipei, Taiwan.|Department of Genetics, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Yen-Hsuan
authors.initials: YH
authors.lastname: Ni
authors.affiliation: Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Hsu
authors.affiliation: Department of Pediatrics, National Taiwan University Children Hospital, National Taiwan University, Taipei, Taiwan.|Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Mei-Hwei
authors.initials: MH
authors.lastname: Chang
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000998:Antiviral Agents / Q000627:therapeutic use; D002648:Child; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D000069078:Seroconversion; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D019259:Lamivudine