EFFICACY OF LAMIVUDINE RETREATMENT IN A PATIENT WITH HEPATITIS-B VIRUS (HBV) RECURRENCE AFTER LIVER-TRANSPLANTATION AND HBV-DNA BREAKTHROUGH DURING THE FIRST TREATMENT

Background Transplantation for terminal hepatitis B virus (HBV) diseas e is aggravated by a high rate of reinfection and disease recurrence. Lamivudine, a new nucleoside analog, is a potent inhibitor of HBV synt hesis, but its use may lead to the emergence of HBV-DNA polymerase mut ants resistant to the drug. Methods and Results. We describe the case of a patient who developed an HBV recurrence after liver transplantati on and was treated with lamivudine, An HBV-DNA breakthrough occurred 7 months after the start of therapy, and the drug was stopped after 9 m onths. The molecular state of HBV-DNA was analyzed, and a mutation in the YMDD (tyrosine, methionine, aspartate, aspartate) locus of HBV-DNA polymerase was identified. Nine months after the suspension of lamivu dine the patient experienced a new hepatic attack accompanied by high HBV-DNA levels. Lamivudine was given again. Serum HBV-DNA levels norma lized after 45 days of re-treatment, but lamivudine-resistant mutants were again the prevalent viral population after 3 months. Conclusions. The case described suggests that re-therapy with lamivudine after a f irst emergence of YMDD mutants is temporarily effective in recontrolli ng HBV synthesis but ultimately induces the accelerated reemergence of a prevalently mutant population of HBV, This emphasizes the need for combined antiviral therapy.