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Hepatitis B virus envelope variation after transplantation with and without hepatitis B immune globulin prophylaxis
Author(s) -
Carman W F,
Trautwein C,
van Deursen J,
Colman K,
Dornan E,
McIntyre G,
Waters J,
Kliem V,
Müller R,
Thomas H C,
Manns M P
Publication year - 1996
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510240304
Subject(s) - hepatitis b immune globulin , hepatitis b virus , virology , liver transplantation , transplantation , medicine , hepatitis b , antibody , epitope , immunology , virus , liver disease , orthohepadnavirus , kidney transplantation , hepadnaviridae , biology , hbsag
Hepatitis B virus (HBV) replicates via an intermediate RNA step. High frequency of polymerase errors with additional selection pressure leads to mutations in the HBV genome. We investigated the number, type, and antigenic effects of mutations in the coding region of the HBV surface antigen in eight patients who underwent orthotopic liver transplantation (OLT) for HBV‐related end‐stage liver disease and were experiencing infection of the graft and who received hepatitis B surface antigen antibody (anti‐HBs) prophylaxis (hepatitis B immune globulin [HBIG]) after OLT. Controls were chronic HBV patients who underwent kidney transplantation and received the same immunosuppressive regime but no HBIG. The S‐gene was amplified from serum before and after transplantation, sequenced, and changes in the genome were analyzed. In the five patients who experienced reinfection while receiving anti‐HBs, clear mutations occurred in the S‐gene. In the patient who did not receive HBIG and those who experienced reinfection only after termination of HBIG, no mutations were found in the S‐gene. In the kidney recipients, mutations in the S‐gene occurred in only one of eight patients. Because the a determinant contains neutralizing epitopes, this region was chosen for antibody binding to quantify antigenic effects of the mutations. The two patients who selected mutations in the a determinant and became reinfected while receiving HBIG had reduced antibody binding after OLT. Our results suggest that HBIG after OLT imposes a selection pressure on the S‐gene, and that mutations are one mechanism for reinfection while receiving HBIG.