Liver graft infection by HBV S-gene mutants in transplant patients receiving long-term HBIg prophylaxis.
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.
Santantonio
T
T
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Germany. t.santantonio@clininf.uniba.it
Gunther
S
S
Sterneck
M
M
Rendina
M
M
Messner
M
M
Launois
B
B
Francavilla
A
A
Pastore
G
G
Will
H
H
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
D006514:Hepatitis B Surface Antigens