title: Hepatitis B virus variants with core gene deletions in the evolution of chronic hepatitis B infection.
abstract: OBJECTIVE
  Genomic variants of the hepatitis B virus (HBV) with core gene deletions have been identified in patients with chronic active hepatitis B, but the significance of these mutations in the course of chronic HBV infection remains unknown. The aim of this study was to longitudinally analyze the changes of HBV core gene deletion variants under the enhanced immune pressure of interferon alfa treatment and hepatitis B e antigen (HBeAg) to antibody to hepatitis B e antigen (anti-HBe) seroconversion.
  
  
  METHODS
  HBV precore/core gene was amplified in 358 serum samples from 67 chronic HBV carriers (all HBeAg-positive) followed up for a period of 2-11 years. The core gene deletions were analyzed by gel electrophoresis, cloning, and DNA sequencing.
  
  
  RESULTS
  HBV mutants with core gene deletions (37-250 base pairs) were detected in patients with long-standing HBV replication and ongoing hepatic inflammation, always together with the wild-type strain. They were associated with a significantly lower level of viremia and a high rate of seroconversion to anti-HBe. Core gene deletion mutants were preferentially eliminated after seroconversion, in contrast to the accumulation of HBV strains with a precore stop codon.
  
  
  CONCLUSIONS
  These data indicate that HBV variants with core gene deletions may inhibit HBV replication, do not persist in preference of the wild-type HBV under enhanced immune pressure, and do not confer resistance to interferon alfa treatment.
authors.affiliation: Institute of Liver Studies, King's College School of Medicine and Dentistry, London, England.
authors.forename: G
authors.initials: G
authors.lastname: Marinos
authors.forename: F
authors.initials: F
authors.lastname: Torre
authors.forename: S
authors.initials: S
authors.lastname: Günther
authors.forename: M G
authors.initials: MG
authors.lastname: Thomas
authors.forename: H
authors.initials: H
authors.lastname: Will
authors.forename: R
authors.initials: R
authors.lastname: Williams
authors.forename: N V
authors.initials: NV
authors.lastname: Naoumov
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D002908:Chronic Disease; D005260:Female; D017353:Gene Deletion; D005814:Genes, Viral; D006509:Hepatitis B / Q000276:immunology / Q000628:therapy / Q000821:virology*; D006510:Hepatitis B Antibodies / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011994:Recombinant Proteins; D014758:Viral Core Proteins / Q000235:genetics*
chemical_list: D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014758:Viral Core Proteins