Multicenter Study of Lamivudine Therapy for Hepatitis B... : Hepatology (original) (raw)

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Multicenter Study of Lamivudine Therapy for Hepatitis B After Liver Transplantation

Perrillo, Robert M.D.*,1; Rakela, Jorge2; Dienstag, Jules3; Levy, Gary4; Martin, Paul5; Wright, Teresa6; Caldwell, Stephen7; Schiff, Eugene8; Gish, Robert9; Villeneuve, Jean Pierre10; Farr, Gist11; Anschuetz, Gaya12; Crowther, Lynn12; Brown, Nathaniel12

1_Section of Gastroenterology, Ochsner Clinic, New Orleans, LA; Research Triangle Park NC_

2_University of Pittsburgh Medical Center, Pittsburgh, PA; Research Triangle Park NC_

3_Gastrointestinal Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, MA; Research Triangle Park NC_

4_Toronto General Hospital, Toronto, Canada; Research Triangle Park NC_

5_The University of California Los Angeles School of Medicine, Los Angeles, CA; Research Triangle Park NC_

6_The University of California San Francisco, San Francisco, CA, Research Triangle Park NC_

7_The University of Virginia Health Science Center, Charlottesville, VA; Research Triangle Park NC_

8_The University of Miami, Miami, FL; Research Triangle Park NC_

9_California Pacific Medical Center, San Francisco, CA; Research Triangle Park NC_

10_Centre Hospitalier de l'Universite de Montreal, Montreal, Canada; Research Triangle Park NC_

11_Section of Pathology, Ochsner Clinic, New Orleans, LA; Research Triangle Park NC_

12_Glaxo Wellcome Inc., Research Triangle Park, NC_

* Section of Gastroenterology and Hepatology, Ochsner Clinic, 1514 Jefferson Highway, New Orleans, LA 70121. fax: 504–842–7466; E-mail: [email protected].

Received: 26 August 1998; Accepted: 11 February 1999

Abstract

Hepatitis B after liver transplantation is often fatal, and no proven medical therapy exists for this condition. We chose to study the potential efficacy of lamivudine therapy for patients with chronic hepatitis B after liver transplantation. Fifty–two patients with chronic hepatitis B after liver transplantation were treated in an open label, multicenter study. Each had detectable 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 undetectability of HBV DNA; secondary endpoints included normalization of serum alanine transaminase (ALT) levels, disappearance of hepatitis B e antigen, and improvement in liver histology. After treatment, 60% of patients had undetectable HBV DNA by solution hybridization assay, 14 (31%) of the initially positive patients lost hepatitis B e antigen; hepatitis B surface antigen was undetectable in 3 (6%); and serum ALT levels normalized in 71%. Blinded histological 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 drug resistance, were detected in 14 (27%) of the patients. Repeat liver biopsies 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 therapy for hepatitis B after liver transplantation.