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 with very low dose hepatitis B immu

Abstract

Recurrent hepatitis B virus (HBV)infection remains a major cause of morbidity and mortality after liver transplantation. Recently, antiviral therapy, such as lamivudine, has become available for prophylaxis against HBV reactivation 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 mutant HBV infection not receiving lamivudine (n ‫؍‬ 10); group 2, recurrent precore mutant HBV infection posttransplantation subsequently treated with lamivudine (n ‫؍‬ 10); and group 3, HBV precore mutant patients undergoing liver 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 11 months. Six of these 10 patients developed mutations in the HBV polymerase 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 surface antigen negative and HBV DNA negative. In conclusion, lamivudine therapy in association with low-dose HBIG is effective in preventing HBV reactivation posttransplantation. Rescue therapy with lamivudine in patients with HBV recurrence is only moderately effective, with a 60% lamivudine resistance rate in patients treated for longer than 6 months.

A multicenter United States—Canadian trial to assess lamivudine monotherapy before and after liver transplantation for chronic hepatitis B

“…These encouraging results have given rise to pilot studies in which low-dose HBIg delivered intramuscularly has been given in combination with lamivudine. 33,34 The low doses of HBIg given in these studies minimize the cost as well as adverse effects and, when used in combination with lamivudine, may ultimately prove to have advantages over the use of high-dose HBIg alone. Future studies using a combination of HBIg and lamivudine in a large enough group of patients to adequately assess treatment efficacy are needed to assess the optimal form of prophylactic therapy.…”

Combination Low-Dose Hepatitis B Immune Globulin and Lamivudine Therapy Provides Effective Prophylaxis Against Posttransplantation Hepatitis B

“…10 Early experience in a small group of patients indicated that this may be effective when used in combination with lamivudine. 11 As a result, this approach been used since 1996 in most transplant centers in Australia and New Zealand.…”

Hepatitis B: Progress in the last 15 years

“…Numerous series reported since 1996 showed that LAM has profound antiviral activity, with complete suppression of HBV DNA in 60% to 100% of treated patients. [62][63][64][65][66][67][68] Remarkably, 6% to 45% of treated patients in some series, but not others, became HBsAg negative. 63,65,68 Viral suppression resulted in normalization of alanine aminotransferase levels in 27% to 100% of patients and significant improvement in serum bilirubin and albumin levels.…”