title: Liver graft infection by HBV S-gene mutants in transplant patients receiving long-term HBIg prophylaxis.
abstract: OBJECTIVE
  HBV reinfection of transplant livers occurs frequently even in the presence of high doses of anti-HBs immunoglobulins. We analyzed, retrospectively, whether and which type of S-gene variants were selected by long-term polyclonal anti-HBs (HBIg) treatment leading to reinfection of patients transplanted because of chronic HBs-positive end-stage liver disease.
  
  
  METHODS
  The preS2/S gene of the viral genomes obtained from sera before transplantation and during HBV reinfection was amplified by PCR and directly sequenced.
  
  
  RESULTS
  According to transaminase and HBV DNA hybridization analysis, 3/18 (17%) liver transplant patients had HBV and hepatitis recurrence during anti-HBs therapy. A HBV S-gene mutant containing a G to A nucleotide mutation at position 587, converting Glycine to Arginine (G145A), was identified in all three patients as the dominant population at reinfection but not pre-transplantation. Contrary to the S-gene, no consistent nucleotide changes were found in the pre-S2 region of HBV genomes when comparing the reinfection and pre-transplantation samples.
  
  
  CONCLUSIONS
  These data demonstrate that long-term polyclonal anti-HBs immunoprophylaxis selected the most commonly described G145R S-gene escape HBV variant which became the dominant virus population and was responsible for graft infection. Therefore, immunoglobulins with high affinity for the G145R HBs variant should be included in HBIg to prevent recurrent HBV infection in transplant patients.
authors.affiliation: Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Germany. t.santantonio@clininf.uniba.it
authors.forename: T
authors.initials: T
authors.lastname: Santantonio
authors.forename: S
authors.initials: S
authors.lastname: Gunther
authors.forename: M
authors.initials: M
authors.lastname: Sterneck
authors.forename: M
authors.initials: M
authors.lastname: Rendina
authors.forename: M
authors.initials: M
authors.lastname: Messner
authors.forename: B
authors.initials: B
authors.lastname: Launois
authors.forename: A
authors.initials: A
authors.lastname: Francavilla
authors.forename: G
authors.initials: G
authors.lastname: Pastore
authors.forename: H
authors.initials: H
authors.lastname: Will
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000821:virology*; D006801:Humans; D007116:Immunization, Passive; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D006514:Hepatitis B Surface Antigens