Experience with lamivudine therapy for hepatitis B virus infection before and after liver transplantation, and review of the literature

Objectives. To analyse the results of lamivudine therapy on suppression of hepatitis B virus (HBV) replication before transplantation and on preventing graft reinfection postoperatively. Design. Long-term clinical study. Setting. Liver Institute and Department of Transplantation of a tertiary-care university-affiliated centre. Subjects. (1) 14 candidates for liver transplantation with decompensated liver disease caused by active replication of HBV; (2) six patients with recurrent HBV infection after transplantation. Intervention. Lamivudine 100 mg daily; administered in group 1 before surgery and continued after in nine patients who underwent transplantation; administered in group two postoperatively only. antihepatitis B surface antigen immunoglobulin (HBIg) was administered postoperatively in both groups. Main outcome measures. Immunoassay evaluation of serum hepatitis B surface antigen, serum hepatitis Be antigen and serum HBV DNA (hybridization and PCR); sequencing through the tyrosine-methionine-aspartate-aspartate locus of the HBV polymerase gene in patients with lamivudine breakthrough; inflammation and fibrosis scoring on liver biopsy before and at least 2 years after lamivudine therapy in group 2. Results. Pretransplantation therapy (group 1) significantly suppressed HBV replication and enabled nine patients (64.2%) to undergo transplantation. Only one patient (7.1%) had lamivudine breakthrough, and one (7.1%) had recurrent HBV. Lamivudine administration begun after transplantation (mean 48.0 months, range 30-60 months) because of graft reinfection (group 2) was associated, over the long-term, with the emergence of high mutation rates (83.3%), histological disease progression (66.6%), and hepatic failure (33.3%). Conclusions. In patients with chronic HBV infection and active viral replication, lamivudine therapy is effective when started before transplantation. However, its long-term administration after transplantation for recurrent HBV leads to high resistance rates. Combination therapy with lamivudine and HBIg immunoglobulin cart substantially reduce the recurrence rate. Further studies on combination antiviral therapy are needed in this patient population.