Liver graft infection by HBVS-gene mutants in transplant patients receiving long-term HBlg prophylaxis

BACKGROUND/AIMS: HBV reinfection of transplant livers occurs frequently eve n in the presence of high doses of anti-HBs immunoglobulins. We analyzed, r etrospectively, whether and which type of S-gene variants were selected by long-term polyclonal anti-HBs (HBIg) treatment leading to reinfection of pa tients transplanted because of chronic HBs-positive end-stage liver disease . METHODOLOGY: The preS2/S gene of the viral genomes obtained from sera befor e transplantation and during HBV reinfection was amplified by PCR and direc tly sequenced. RESULTS: According to transaminase and HBV DNA hybridization analysis, 3/18 (17%) liver transplant patients had HBV and hepatitis recurrence during an ti-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-t ransplantation. Contrary to the S-gene, no consistent nucleotide changes we re 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 immu noprophylaxis 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 G145 R HBs variant should be included in HBIg to prevent recurrent HBV infection in transplant patients.