Clinical Trial: Randomized controlled trial of zidovudine and lamivudine for patients with primary biliary cirrhosis stabilized on ursodiol.
Author(s): Mason AL, Lindor KD, Bacon BR, Vincent C, Neuberger JM, Wasilenko ST
Affiliation(s): Department of Medicine, University of Alberta, Edmonton, AB, Canada.
Publication date & source: 2008-07-09, Aliment Pharmacol Ther., [Epub ahead of print]
Background: A human betaretrovirus has been characterized in patients with primary biliary cirrhosis (PBC). Uncontrolled studies using combination anti-retroviral therapy have reported significant biochemical and histological improvement. Our aim was to conduct a double blind, randomized controlled trial as a proof of principal to link infection with PBC. Methods: 59 patients with an alkaline phosphatase level > 1.5 upper limits of normal stabilized on ursodeoxycholic acid therapy were randomized to either 300mg zidovudine and 150mg lamivudine B.I.D. or placebo for 6 months. Results: None of the patients normalized alkaline phosphatase and no significant differences were observed in normalizing serum aminotransferase levels. Significant differences were observed in the antiviral versus placebo arms with improvements in serial alkaline phosphatase (p<0.04), ALT (p<0.03) and AST (p<0.04) as well as clinical score (p<0.02). After 6 months, 25% of patients in the placebo arm and 4% in the antiviral arm had evidence of virus in serum. Conclusions: The study endpoints for normalizing hepatic biochemistry were too stringent to show efficacy for zidovudine and lamivudine therapy despite the demonstrable impact on clinical and biochemical improvement. Accordingly, more potent anti-viral regimens will be required to confirm the efficacy of antiviral therapy in PBC patients with human betaretrovirus infection.