Multicenter study of lamivudine therapy for hepatitis B after liver transplantation. Lamivudine Transplant Group.
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.
Perrillo
R
R
Section of Gastroenterology, Ochsner Clinic, New Orleans, LA 70121, USA. rperrillo@Ochsner.org
Rakela
J
J
Dienstag
J
J
Levy
G
G
Martin
P
P
Wright
T
T
Caldwell
S
S
Schiff
E
E
Gish
R
R
Villeneuve
J P
JP
Farr
G
G
Anschuetz
G
G
Crowther
L
L
Brown
N
N
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*
D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine