Liver graft infection by HBV S-gene mutants in transplant patients receiving long-term HBIg prophylaxis

Teresa Santantonio, Stephan Gunther, Martina Sterneck, Maria Rendina, Michel Messner, Bernard Launois, Antonio Francavilla, Giuseppe Pastore, Hans Will

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND/AIMS: 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. METHODOLOGY: 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.

Original languageEnglish
Pages (from-to)1848-1854
Number of pages7
JournalHepato-Gastroenterology
Volume46
Issue number27
Publication statusPublished - 1999

Keywords

  • Graft infection
  • HBV reinfection
  • HBV variants
  • Hepatitis B immunoglobulin
  • Liver transplantation
  • S-gene mutant

ASJC Scopus subject areas

  • Gastroenterology

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