title: Clinical relevance of precore and basal core promoter variants of hepatitis B virus during natural hepatitis B e antigen seroconversion may be overstated.
abstract: BACKGROUND
  Clinical relevance of nucleotide changes in precore and basal core promoters in the hepatitis B virus genome during hepatitis B e antigen seroconversion may be overstated. The authors investigated the existence and changes in the relative proportion of variants to wild virus that occur with seroconversion.
  
  
  METHODS
  Sera from 30 school-aged long-term hepatitis B virus carriers, including 11 tested before and after seroconversion during 1 to 8 years of follow-up, were evaluated for variations in nucleotide sequences of the basal core promoter (T1762 and A1764), precore region (A1869), and carboxyl-terminus of the X region of the hepatitis B virus genome using an amplification refractory mutation detection system with mutant-specific primers.
  
  
  RESULTS
  All variants were found to already exist before seroconversion at various wild-type/mutant ratios. The positive rates of these variants were not changed with loss of hepatitis B e antigen. Although there was a relative increase in the concentration of these mutants in wild-type/mutant mixed populations, most patients with only a wild-type population maintained the same pattern after loss of hepatitis B e antigen.
  
  
  CONCLUSIONS
  Our results indicate that hepatitis B virus exists as a quasi species, and correlations of nucleotide sequences with clinical and serologic findings must be done with caution.
authors.affiliation: Second Department of Internal Medicine, Shimane Medical University, Izumo-city, Shimane, Japan. rfukuda@shimane-u.ac.jp
authors.forename: R
authors.initials: R
authors.lastname: Fukuda
authors.forename: R
authors.initials: R
authors.lastname: Mohammad
authors.forename: S
authors.initials: S
authors.lastname: Hamamoto
authors.forename: N
authors.initials: N
authors.lastname: Ishimura
authors.forename: S
authors.initials: S
authors.lastname: Ishihara
authors.forename: S
authors.initials: S
authors.lastname: Akagi
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D000293:Adolescent; D002648:Child; D003430:Cross-Sectional Studies; D017931:DNA Primers; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D014644:Genetic Variation; D016679:Genome, Viral; D006509:Hepatitis B / Q000276:immunology / Q000821:virology*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D015995:Prevalence; D011401:Promoter Regions, Genetic; D012680:Sensitivity and Specificity
chemical_list: D017931:DNA Primers; D006513:Hepatitis B e Antigens