Liver transplantation for chronic hepatitis B infection with the use of combination lamivudine and low-dose hepatitis B immune globulin

Abstract

Current protocols for prophylaxis against allograft reinfection after liver transplantation for chronic hepatitis B virus (HBV) infection include the administration of large doses of hepatitis B immune globulin (HBIG), with considerable associated economic costs. Monotherapeutic prophylaxis with lamivudine has been complicated by the development of resistant strains of HBV. We studied the effectiveness of a posttransplantation prophylaxis protocol using combination lamivudine and low-dose HBIG in 7 consecutive patients with chronic HBV infection, 4 of whom were serum HBV DNA positive before pretransplantation lamivudine therapy. All patients were serum HBV DNA negative at transplantation and received lamivudine, 100 mg/d, posttransplantation. HBIG, 2170 IU, was administered intramuscularly intraoperatively and daily for 14 days. Maintenance HBIG therapy consisted of 2170 IU intramuscularly twice weekly, tapered to every 2 to 4 weeks by 12 months posttransplantation.Target serum HBIG (HBV surface antibody) titers were less than 500 IU/L for 6 months, then greater than 300 IU/L until 12 months posttransplantation. Induction serum HBIG titers were determined daily in 5 patients, and both serum HBIG and hepatitis B surface antigen were determined every 4 weeks in all patients. One patient died 61 days posttransplantation; the surviving patients (n ‫؍‬ 6) were followed up for a mean of 532 days (range, 395 to 648 days). No patient has developed allograft reinfection. In the induction period, a target HBIG titer of greater than 500 IU/L was not achieved until a mean of 6.8 days (range, 5 to 10 days). In the maintenance period, all patients achieved the target HBIG titer. This suggests combination lamivudine and low-dose HBIG is effective in preventing allograft reinfection by HBV.

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.…”

An efficacy and cost-effectiveness analysis of combination hepatitis B immune globulin and lamivudine to prevent recurrent hepatitis B after orthotopic liver transplantation compared with hepatitis B immune globulin monotherapy

“…7,10,11 In previous studies, combination lamivudine and HBIG prevented HBV recurrence in all patients with no evidence of the development of lamivudine-resistant escape mutants during long-term follow-up. [12][13][14] In the present study, with our expanded experience in a larger cohort of patients administered combination HBIG and lamivudine to prevent recurrent HBV post-OLT, we evaluate the efficacy and cost-effectiveness of this strategy to prevent HBV recurrence compared with standard HBIG monotherapy. …”

Late hepatic allograft dysfunction

“…46 HBV recipients receiving the combination of HBIG therapy and lamivudine have virtually eliminated recurrence of HBV disease. 47,48 However, patients treated with long-term lamivudine alone have experienced the appearance of YMDD mutants in about one third of patients at the end of 2 years of treatment. 46,49 However, adefovir has recently been shown to effectively treat the lamivudine-resistant hepatitis B mutants and, thus, may be useful in treating liver transplant recipients developing the YMDD mutant.…”