title: Long-term follow-up of children with postnatal immunoprophylaxis failure who were infected with hepatitis B virus surface antigen gene mutant.
abstract: BACKGROUND
  The long-term evolution and outcomes of infection with a hepatitis B virus (HBV) surface antigen (HBsAg) gene mutant (hereafter, "HBsAg-mutant HBV") among immunized children remain unclear.
  
  
  METHODS
  Ninety-five HBsAg-positive children aged 0.5-18.4 years (mean age, 5.8 years) who did not respond to postnatal immunoprophylaxis were prospectively followed for 1-22.8 years (mean follow-up, 8.5 years). Clinical, serologic, and virologic features were compared between 38 untreated HBV e antigen (HBeAg)-positive children carrying HBsAg-mutant HBV (group 1) and 49 children carrying wild-type HBV (group 2). HBsAg-mutant HBV was examined in 20 immunized children presenting with HBV-related hepatocellular carcinoma (HCC).
  
  
  RESULTS
  The initial alanine aminotransferase (ALT) level, the maximal ALT level during the HBeAg-positive phase of HBV infection, the cumulative incidence of HBeAg seroconversion (P = .0018), and the rate of low serum HBV DNA load (defined as <10 copies/mL) at the last visit (P = .006) were higher in group 1 than in group 2. A higher frequency of HBV genotype C and a higher ALT level during surface mutant viremia were observed in codon 110-129 mutants than in codon 144-145 mutants. None of the 95 patients developed cirrhosis or HCC. HBsAg-mutant HBV was detected in 3 of 8 (38%) HBV DNA-positive children with HCC.
  
  
  CONCLUSIONS
  HBeAg-positive immunized children carrying HBsAg-mutant HBV may develop hepatitis activity, HBeAg seroconversion, and a low viremic state earlier than those carrying wild-type HBV. Continuous monitoring of children with wild-type HBV infection and those with HBsAg-mutant HBV for possible development of HCC is needed.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Hsu
authors.forename: Mei-Hwei
authors.initials: MH
authors.lastname: Chang
authors.forename: Yen-Hsuan
authors.initials: YH
authors.lastname: Ni
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Cheng-Lun
authors.initials: CL
authors.lastname: Chiang
authors.forename: Huey-Ling
authors.initials: HL
authors.lastname: Chen
authors.forename: Jia-Feng
authors.initials: JF
authors.lastname: Wu
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000473:pathology / Q000821:virology; D002648:Child; D002675:Child, Preschool; D003062:Codon; D004279:DNA, Viral / Q000097:blood; D019143:Evolution, Molecular; D005500:Follow-Up Studies; D005814:Genes, Viral; D005838:Genotype; D006510:Hepatitis B Antibodies / Q000627:therapeutic use*; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000627:therapeutic use*; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000628:therapy* / Q000821:virology; D006801:Humans; D007114:Immunization; D015994:Incidence; D007223:Infant; D008113:Liver Neoplasms / Q000276:immunology / Q000821:virology; D008137:Longitudinal Studies; D011446:Prospective Studies; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load; D014766:Viremia / Q000473:pathology / Q000821:virology
chemical_list: D003062:Codon; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase