Multicenter study of lamivudine therapy for hepatitis B after liver transplantation

Hepatitis B after liver transplantation is often fatal, and no proven medic al therapy exists for this condition. We chose to study the potential effic acy of lamivudine therapy for patients with chronic hepatitis B after liver transplantation. Fifty-two patients with chronic hepatitis B after liver t ransplantation were treated in an open label, multicenter study. Each had d etectable hepatitis B virus (HBV) DNA in serum and 45 (87%) had detectable serum hepatitis B e antigen before treatment. Patients were treated for 52 weeks with lamivudine (100 mg daily). The primary endpoint was undetectabil ity of HBV DNA; secondary endpoints included normalization of serum alanine transaminase (ALT) levels, disappearance of hepatitis B e antigen, and imp rovement in liver histology. After treatment, 60% of patients had undetecta ble HBV DNA by solution hybridization assay, 14 (31%) of the initially posi tive patients lost hepatitis B e antigen; hepatitis B surface antigen was u ndetectable in 3 (6%); and serum ALT levels normalized in 71%. Blinded hist ological assessments showed improvement in the histological activity index (P = .007 for periportal necrosis, .001 for lobular necrosis, and .013 for portal inflammation). YMDD variants of HBV, potentially associated with dru g resistance, were detected in 14 (27%) of the patients. Repeat liver biops ies in 7 patients with the mutated virus were unchanged in 2, improved in 2 , and worse in 3. We conclude that lamivudine is a potentially effective th erapy for hepatitis B after liver transplantation.