LAMIVUDINE FOR HEPATITIS B IN LIVER TRANSPLANTATION

Abstract

Liver transplantation for hepatitis B virus (HBV) has been associated with a high rate of reinfection and graft failure. Lamivudine, a potent inhibitor of HBV replication, has been shown to prevent viral recurrence after transplantation. The effectiveness of lamivudine monotherapy for the management of HBV recurrence after liver transplantation was assessed. Lamivudine was used in three patient groups: (1) patients started before transplantation and continued after transplantation (n = 13); (2) patients treated after transplantation (n = 15); and (3) patients with de novo hepatitis B after transplantation (n = 4). Median follow-up on lamivudine was 24 months. Active viral replication (HBV-DNA+) was seen in 17 (53%) of 32 at treatment initiation. All lost HBV-DNA at a mean of 2.4+/-1.6 months after lamivudine initiation. Twenty-six (81%) patients remain free of viral recurrence. Six (19%) patients have evidence of breakthrough infection with the YMDD mutant of HBV, two of whom progressed to graft failure. All four patients in group 1 who developed breakthrough had evidence of hepatitis B surface antigen expression in the explanted liver by immunohistochemistry despite being serum HBV-DNA negative before transplantation. No difference was observed among the three groups in DNA clearance or breakthrough rates. Lamivudine achieves viral DNA clearance in almost all patients. Expression of viral antigens in the liver seems to identify patients at risk of developing HBV-DNA recurrence. Disease-free survival of 81% at 22 months is similar to data with hepatitis B immunoglobulin therapy. Given the safe clinical profile and high efficacy in the prevention of disease recurrence, lamivudine will favorably change the outlook of liver transplantation for HBV.