title: Identification of a novel pre-S2 mutation in a subgroup of chronic carriers with spontaneous clearance of hepatitis B virus surface antigen.
abstract: OBJECTIVE
  The aim of the present study was to investigate whether spontaneous seroclearance of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B could be attributed to the presence of pre-S/S gene mutations.
  
  
  METHODS
  Of 34 hepatitis B virus (HBV) carriers who experienced spontaneous seroclearance of HBsAg, 30 were still seropositive for HBV DNA. The serum samples of these carriers were subjected to sequence analysis.
  
  
  RESULTS
  A novel pre-S2 mutation, G149R, was found in nine (group I) but not in 17 (group II) patients carrying HBV DNA with intact pre-S/S reading frames. In the remaining four patients (group III), only aberrant pre-S/S transcripts were found in their sera. Distinct patterns of amino acid substitutions specific to group I and II patients were identified. Superinfection by hepatitis C or D virus occurred predominantly in group II patients (P = 0.019). Superinfection by HBV of a different genotype occurred predominantly in patients without hepatitis C or D virus superinfection (P = 0.013). Site-directed mutagenesis experiments showed that secretion of HBsAg was not defective in the pre-S2 G149R mutant.
  
  
  CONCLUSIONS
  In a particular subgroup (group I) of patients, seroclearance of HBsAg was not caused by superinfection of other hepatitis viruses, nor was it caused by failure of HBsAg secretion or detection. Instead, a yet unrecognized mechanism associated with emergence of a novel pre-S2 mutation is responsible.
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital and Chang Gung University School of Medicine, Taipei, Taiwan. catyeh@ms14.hinet.net
authors.forename: Chau-Ting
authors.initials: CT
authors.lastname: Yeh
authors.forename: Mei-Hui
authors.initials: MH
authors.lastname: Chang
authors.forename: Hsin-Yu
authors.initials: HY
authors.lastname: Lai
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Chang
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Chu
authors.forename: Yun-Fan
authors.initials: YF
authors.lastname: Liaw
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002353:Carrier State / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood* / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011498:Protein Precursors / Q000235:genetics*; D016364:Reading Frames; D020539:Sequence Analysis, Protein; D015163:Superinfection / Q000821:virology
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; C050807:presurface protein 2, hepatitis B surface antigen