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.
We conducted a randomized trial in seven Australian hospitals of the efficacy and safety of three immunosuppressive regimens after first transplantation of a cadaver kidney: long-term cyclosporine, short-term (three months) cyclosporine followed by azathioprine and prednisolone, and azathioprine and prednisolone without cyclosporine. Patients assigned to long-term cyclosporine (n = 138) or short-term cyclosporine followed by azathioprine and prednisolone (n = 141) had similar actuarial 12-month survival (98.4 vs. 96.4 percent) and graft survival (83.9 vs. 82.1 percent). Patients assigned to receive only azathioprine and prednisolone (n = 138), with optional use of antithymocyte globulin, had a significantly poorer survival rate (91.3 percent, P = 0.015) because of deaths from cardiac causes and infection, but their graft survival of 76.0 percent (P = 0.31) did not differ significantly from that of either group receiving cyclosporine. After the switch from cyclosporine to azathioprine and prednisolone, 15 percent of patients had reversible rejection episodes, but the frequency of rejection and graft loss did not differ from that in the long-term cyclosporine group. After the change to azathioprine and prednisolone, serum creatinine levels declined in nearly all patients, so that after three months they were comparable to those in the group receiving azathioprine and prednisolone only, and significantly lower than those in the group receiving long-term cyclosporine therapy (P less than 0.003). We conclude that the two cyclosporine regimens result in comparable patient and graft survival, but that changing to azathioprine and prednisolone at three months improves graft function.
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