A Multicenter United States—Canadian Trial to Assess... : Hepatology (original) (raw)

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A Multicenter United States—Canadian Trial to Assess Lamivudine Monotherapy Before and After Liver Transplantation for Chronic Hepatitis B

Perrillo, Robert P. M.D.*,1; Wright, Teresa2; Rakela, Jorge3; Levy, Gary4; Schiff, Eugene5; Gish, Robert6; Martin, Paul7; Dienstag, Jules8; Adams, Paul9; Dickson, Rolland10; Anschuetz, Gaya11; Bell, Steve11; Condreay, Lynn11; Brown, Nathaniel11 The Lamivudine North American Transplant Group

1_Section of Gastroenterology and Hepatology, Ochsner Clinic, New Orleans, LA_

2_Gastroenterology Division, Veterans Affairs Medical Center, San Francisco, CA_

3_Division of Gastroenterology, University of Pittsburgh Medical Center, Pittsburgh, PA_

4_Toronto General Hospital, Toronto, Canada_

5_Center for Liver Diseases, University of Miami Medical Center, Miami, FL_

6_California Pacific Medical Center, San Francisco, CA_

7_Division of Gastroenterology, UCLA Medical Center, Los Angeles, CA_

8_Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA_

9_London Health Sciences Center, London/Ontario, Canada_

10_University of Florida, Gainesville, FL_

11_Glaxo Wellcome, Research Triangle Park, NC_

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

Received: 15 May 2000; Accepted: 9 November 2000

Abstract

Seventy–seven liver transplant candidates were enrolled in a multicenter study in which patients were treated with lamivudine (100 mg daily) without the adjunctive use of hepatitis B immune globulin. Treatment was begun while patients awaited liver transplantation and continued after transplantation. All were hepatitis B surface antigen (HBsAg) positive, and 61% had detectable hepatitis B e antigen (HBeAg) and HBV DNA when treatment was begun. Forty–seven underwent liver transplantation and 30 did not. Median study participation was 38 months (range, 2.7–48.5) in the transplanted patients and 26 months (range, 0.1–37) in the nontransplanted group. Twenty–five of 42 (60%) transplanted patients with 12 or more weeks of posttransplantation follow–up were HBsAg negative at the last study visit. At treatment week 156, 13 of 22 (59%) remained HBsAg negative, and all 9 reinfected patients were HBV–DNA positive before treatment. In the nontransplanted patients, HBeAg was initially detectable in 20 of 27 (74%) but this decreased to 3 of 17 (18%) after 104 weeks of treatment, and significant improvement in biochemical parameters was observed. HBV–DNA polymerase mutants were detected in 15 (21%) and 6 (20%) of the transplanted and nontransplanted patients, respectively. When compared with historical cohorts, lamivudine–treated patients appeared to have improved survival, and transplanted patients had a decrease in the rate of recurrent HBV infection. Lamivudine therapy was partially effective in preventing recurrent HBV infection when given before and after transplantation. Thus, future trials using a combination of HBIg and lamivudine are needed to assess the optimal prophylactic therapy.