Lamivudine therapy in patients undergoing liver transplantation for hepatitis B virus precore mutant-associated infection: High resistance rates in treatment of recurrence but universal prevention if used as prophylaxis withvery low dose hepatitis B immune globulin

Recurrent hepatitis B virus (HBV) infection remains a major cause of morbid ity and mortality after liver transplantation. Recently, antiviral therapy, such as lamivudine, has become available for prophylaxis against HBV react ivation posttransplantation and for the treatment of HBV recurrent disease. We report our initial experience with lamivudine therapy in patients with precore mutant-associated HBV infection undergoing liver transplantation (n = 29), Outcomes were compared in three patient groups.: group 1, precore m utant HBV infection not receiving lamivudine (n = 10); group 2, recurrent p recore mutant HBV infection posttransplantation subsequently treated with l amivudine (n = 10); and group 3, HBV precore mutant patients undergoing liv er transplantation and receiving lamivudine and low-dose hepatitis B immune globulin (HBIG) from the time of transplantation (n = 9), In group 1, HBV recurred in 9 of 10 patients, with subsequent graft loss in all 9 patients. In group 2, all patients developed HBV recurrence at a mean of 7.3 months posttransplantation and started lamivudine therapy at a median of 16 months posttransplantation. Follow-up on lamivudine therapy was for a median of 1 1 months. Six of these 10 patients developed mutations in the HBV polymeras e gene associated with lamivudine resistance. There were two liver failure- related deaths in this group. In group 3 patients, there was one death from graft-versus-host disease. The remaining 8 patients have been followed up for a mean of 15.6 months posttransplantation, and all remain hepatitis B s urface antigen negative and HBV DNA negative. In conclusion, lamivudine the rapy in association with low-dose HBIG is effective in preventing HBV react ivation posttransplantation. Rescue therapy with lamivudine in patients wit h HBV recurrence is only moderately effective, with a 60% lamivudine resist ance rate in patients treated for longer than 6 months. Copyright (C) 1999 by the American Association for the Study of Liver Diseases.