title: Emergence of hepatitis B virus S gene mutants in patients experiencing hepatitis B surface antigen seroconversion after peginterferon therapy.
abstract: With anti-hepatitis B virus (anti-HBV) therapy using peginterferon, the seroconversion of hepatitis B surface antigen (HBsAg), which is considered a cure of the disease, can be achieved in a small percentage of patients. Eight of 245 consecutive patients (3.27%) with chronic hepatitis B who received peginterferon therapy at our center achieved HBsAg seroclearance. Surprisingly, two of the eight patients remained viremic according to standard HBV DNA assays. The coding regions of the HBV pre-S/S gene, which were derived from serial serum samples, were analyzed. Site-directed mutagenesis experimentation was performed to verify the phenotypic alterations in Huh-7 cells. In patient 1, an sT125A mutant developed during the HBsAg-negative stage and constituted 11.2% of the viral population. The HBV DNA level was 2.73 × 10(4) IU/mL at the time of detection. This mutant was not detectable in the HBsAg-positive stages. A phenotypic study of Huh-7 cells showed a significant reduction of antigenicity. In patient 2, an sW74* truncation mutation was found during the HBsAg-negative stage and constituted 83.1% of the viral population. The HBV DNA level was 4.12 × 10(4) IU/mL at the time of detection. A phenotypic study of Huh-7 cells showed a complete loss of antigenicity. Patient 2 subsequently experienced an episode of hepatitis relapse 7 months after the end of treatment and was negative for HBsAg throughout the hepatitis flare.
  
  
  CONCLUSIONS
  During antiviral therapy with peginterferon, the achievement of HBsAg seroconversion does not necessarily indicate viral eradication. The emergence of S gene mutants is another possibility, and a relapse with HBsAg-negative hepatitis can occur.
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Chao-Wei
authors.initials: CW
authors.lastname: Hsu
authors.forename: Chau-Ting
authors.initials: CT
authors.lastname: Yeh
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D001706:Biopsy; D004279:DNA, Viral / Q000097:blood; D005814:Genes, Viral / Q000235:genetics*; D005838:Genotype; D006509:Hepatitis B / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a