title: Analysis of S gene mutation of the hepatitis B virus in adult liver transplant recipients showing resistance to hepatitis B immunoglobulin therapy.
abstract: BACKGROUND
  A considerable proportion of recipients of liver transplantations who are presented hepatitis B immunoglobulin (HBIG) monotherapy for hepatitis B virus (HBV) prophylaxis develop HBIG resistance. In this study, we investigated the mutation patterns in the major hydrophilic region (MHR) of amino acid sequences 100 to 160.
  
  
  METHODS
  Using the gene sequence analyzer for amino acid sequences 0 to 226 in the S/pre-S region we analyzed blood samples of 15 patients showing HBIG resistance after high-dose HBIG prophylaxis.
  
  
  RESULTS
  Various mutations in the MHR were observed in 14/15 samples: Gly145Arg mutation in 8/13 Adr subtype and 1/2 Ayw subtype samples (60%). The next most common mutation was Gly165Trp in 8/13 Adr subtype but neither of 2 Ayw subtype samples (53.3%). Concurrent antiviral resistance was noted in 5 patients: lamivudine (n = 5), or entecavir (n = 3), but not adefovir, suggesting the occurrence of simultaneous, antiviral cross-resistances. Two patients underwent retransplantation due to the progression of HBV infection despite vigorous antiviral therapy. At diagnosis of HBV recurrence, the mean HBV DNA load was 6.5 × 10(6) copies/mL; 4 patients showed paradoxical coexistence of anti-HBs and HBsAg. Currently, 2 subjects show low-level HBV DNA replication in peripheral blood, although the other 12 had no DNA replication after prolonged antiviral therapy.
  
  
  CONCLUSIONS
  This study suggested that various mutations in the "a" determinant were associated with HBIG resistance. Since treatment failure to rescue antiviral therapy was often associated with delayed detection of HBV recurrence rather than concurrent antiviral resistance, frequent HBV surveillance using more sensitive screening tests, such as HBeAg and HBV DNA polymerase chain reaction assay, seems to be mandatory.
authors.affiliation: Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: G-C
authors.initials: GC
authors.lastname: Park
authors.forename: S
authors.initials: S
authors.lastname: Hwang
authors.forename: C-S
authors.initials: CS
authors.lastname: Ahn
authors.forename: K-H
authors.initials: KH
authors.lastname: Kim
authors.forename: D-B
authors.initials: DB
authors.lastname: Moon
authors.forename: T-Y
authors.initials: TY
authors.lastname: Ha
authors.forename: G-W
authors.initials: GW
authors.lastname: Song
authors.forename: D-H
authors.initials: DH
authors.lastname: Jung
authors.forename: Y W
authors.initials: YW
authors.lastname: Shin
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.forename: K-H
authors.initials: KH
authors.lastname: Chang
authors.forename: J-M
authors.initials: JM
authors.lastname: Namgoong
authors.forename: C-S
authors.initials: CS
authors.lastname: Park
authors.forename: H-W
authors.initials: HW
authors.lastname: Park
authors.forename: Y-H
authors.initials: YH
authors.lastname: Park
authors.forename: S-H
authors.initials: SH
authors.lastname: Kang
authors.forename: B-H
authors.initials: BH
authors.lastname: Jung
authors.forename: S-G
authors.initials: SG
authors.lastname: Lee
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D024882:Drug Resistance, Viral; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use*; D016031:Liver Transplantation; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D007136:Immunoglobulins