Long-term experience with lamivudine therapy for hepatitis B virus infection after liver transplantation

Abstract

Hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) is associated with a high recurrence rate and poor prognosis. This is the first study of the efficacy of long-term lamivudine therapy for patients with HBV infection after OLT. Eight patients (5 men, 3 women) aged 35 to 63 years (mean, 50 years) with HBV infection after OLT (6 patients, recurrent infection; 2 patients, de novo infection) were treated with lamivudine, 100 mg/d, on a compassionate-use basis. Before treatment, all had detectable HBV DNA in serum, and 5 patients (62.5%) had detectable serum hepatitis Be antigen (HBeAg). Duration of treatment was 24 to 50 months (mean, 36 months). Patients were monitored for serum alanine aminotransferase level (ALT), HBV DNA (by hybridization), hepatitis B surface antigen (HBsAg), and HBeAg before and after therapy, and liver histological findings were scored for inflammation and fibrosis. After treatment, 3 patients (32.5%) had undetectable HBV DNA by hybridization assay. None of the patients lost serum HBeAg and HBsAg, except for 1 patient who lost serum HBeAg and became serum antibody to HBeAg-positive. Serum ALT levels normalized in 5 patients (62.5%). Blinded histological assessment showed improvement in 1 patient, no change in 2 patients, and worsening in 5 patients. YMDD variants of HBV were detected in 5 patients (62.5%) within 9 to 20 months (mean, 13 months) of lamivudine therapy. Of these, 2 patients (40%) had hepatic failure (1 patient died of massive variceal bleed) and 3 patients remain clinically stable. Lamivudine therapy was continued in the latter patients. Although lamivudine is a potentially effective therapy for HBV infection after OLT, emergence of high mutation rates with long-term therapy, histological progression, and the possibility of hepatic failure point to the need to investigative combinations of antiviral therapy.