HEPATITIS-B VIRUS ENVELOPE VARIATION AFTER TRANSPLANTATION WITH AND WITHOUT HEPATITIS-B IMMUNE GLOBULIN PROPHYLAXIS

Hepatitis B virus (HBV) replicates via an intermediate RNA step, High frequency of polymerase errors with additional selection pressure lead s to mutations in the HBV genome. We investigated the number, type, an d antigenic effects of mutations in the coding region of the HBV surfa ce antigen in eight patients who underwent orthotopic liver transplant ation (OLT) for HBV-related end-stage liver disease and were experienc ing infection of the graft and who received hepatitis B surface antige n antibody (anti-HBs) prophylaxis (hepatitis B immune globulin [HBIG]) after OLT, Controls were chronic HBV patients who underwent kidney tr ansplantation and received the same immunosuppressive regime but no HB IG. The S-gene was amplified from serum before and after transplantati on, sequenced, and changes in the genome were analyzed. In the five pa tients who experienced reinfection while receiving anti-HBs, clear mut ations 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, muta tions in the S-gene occurred in only one of eight patients, Because th e 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 becam e reinfected while receiving HBIG had reduced antibody binding after O LT. Our results suggest that HBIG after OLT imposes a selection pressu re on the S-gene, and that mutations are one mechanism for reinfection while receiving HBIG.