title: Multicenter study of lamivudine therapy for hepatitis B after liver transplantation. Lamivudine Transplant Group.
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.
authors.affiliation: Section of Gastroenterology, Ochsner Clinic, New Orleans, LA 70121, USA. rperrillo@Ochsner.org
authors.forename: R
authors.initials: R
authors.lastname: Perrillo
authors.forename: J
authors.initials: J
authors.lastname: Rakela
authors.forename: J
authors.initials: J
authors.lastname: Dienstag
authors.forename: G
authors.initials: G
authors.lastname: Levy
authors.forename: P
authors.initials: P
authors.lastname: Martin
authors.forename: T
authors.initials: T
authors.lastname: Wright
authors.forename: S
authors.initials: S
authors.lastname: Caldwell
authors.forename: E
authors.initials: E
authors.lastname: Schiff
authors.forename: R
authors.initials: R
authors.lastname: Gish
authors.forename: J P
authors.initials: JP
authors.lastname: Villeneuve
authors.forename: G
authors.initials: G
authors.lastname: Farr
authors.forename: G
authors.initials: G
authors.lastname: Anschuetz
authors.forename: L
authors.initials: L
authors.lastname: Crowther
authors.forename: N
authors.initials: N
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine