title: Clinical and virological features of occult hepatitis B in patients with HBsAg seroclearance post-treatment or spontaneously.
abstract: BACKGROUND
  Occult hepatitis B virus (HBV) infection (OHB) may exist in patients experiencing hepatitis B surface antigen (HBsAg) seroclearance.
  
  
  OBJECTIVE
  We examined the clinical and virological features of OHB in patients who lost HBsAg post-treatment or spontaneously.
  
  
  METHODS
  We collected 44 patients with HBsAg seroclearance: 15 patients with dual HBV/hepatitis C virus (HCV) infection who lost HBsAg after peginterferon alfa-2a (PEG-IFN) plus ribavirin therapy; 13 HBV mono-infected patients who lost HBsAg after various oral antiviral therapies; and 16 patients who lost HBsAg spontaneously. OHB was defined as detectable serum HBV DNA in the absence of HBsAg. Viral mutations associated with OHB were identified by comparison with matched controls that remained positive for HBsAg, and further characterized in vitro.
  
  
  RESULTS
  The prevalence of OHB was 34.1% (15/44) in all patients, which was not significantly different among three groups. One mutation in surface promoter/polymerase region, C3050T (preS1T68I), was identified to be associated with the seroclearance of HBsAg in six cases. This mutation does not change the amino acid sequence of the polymerase protein. The S promoter activity was significantly lower in the construct containing C3050T mutation as compared with the wild-type (P = 0.0008). However, this mutation did not affect HBV replication, transcription and translation in the context of the full-length HBV genome. OHB was not rare in patients with HBsAg seroclearance.
  
  
  CONCLUSIONS
  One mutation, C3050T (preS1T68I), decreased S promoter activity; nevertheless, other factors may play more important role in the clearance of HBsAg in these OHB patients.
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Huei-Ru
authors.initials: HR
authors.lastname: Cheng
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
authors.forename: Hui-Lin
authors.initials: HL
authors.lastname: Wu
authors.forename: Ting-Chih
authors.initials: TC
authors.lastname: Chen
authors.forename: Tai-Chung
authors.initials: TC
authors.lastname: Tseng
authors.forename: Chen-Hua
authors.initials: CH
authors.lastname: Liu
authors.forename: Tung-Hung
authors.initials: TH
authors.lastname: Su
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: Ding-Shinn
authors.initials: DS
authors.lastname: Chen
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002460:Cell Line; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D015995:Prevalence; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D014759:Viral Envelope Proteins / Q000235:genetics; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; C118669:S envelope protein, hepatitis B virus; D014759:Viral Envelope Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a
keywords: clearance; mutation; occult hepatitis B; spontaneous HBsAg loss