Original Contribution
The American Journal of Gastroenterology (2004) 99, 2348–2355; doi:10.1111/j.1572-0241.2004.40741.x
Pilot Studies of Single and Combination Antiretroviral Therapy in Patients with Primary Biliary Cirrhosis
Andrew L Mason MBBS, MRCPI1, Gist H Farr MD1, Lizhe Xu PhD1, Stefan G Hubscher MBChB, FRCPath1 and James M Neuberger MD, FRCP1
1Section of Gastroenterology and Hepatology; and Department of Pathology, Ochsner Clinic Foundation, New Orleans, Louisiana; Department of Pathology and Liver Unit, Queen Elizabeth Hospital, University of Birmingham, UK
Correspondence: Andrew L Mason, MBBS, MRCPI, Division of Gastroenterology, University of Alberta, College Plaza, Suite 205, 8215-112 Street, Edmonton, AB, Canada T6G 2C8
Received 22 June 2004; Revised 0000; Accepted 28 June 2004.
Abstract
OBJECTIVE:
Preliminary reports suggest that patients with primary biliary cirrhosis (PBC) have evidence of human betaretrovirus infection. The aim of this study was to determine whether antiviral therapy impacts on the disease process.
METHODS:
We conducted two consecutive open-labeled, nonrandomized, 1-yr pilot studies; the first with lamivudine 150 mg/day and the second with Combivir combination therapy using lamivudine 150 mg and zidovudine 300 mg twice a day. Eleven PBC patients enrolled in each study, seven patients were entered into both studies, and one patient was withdrawn from each study due to side effects.
RESULTS:
Evaluation of liver biopsies before and after lamivudine therapy showed a 4–5 increase in necroinflammatory score, a 1–1.5 elevation in bile duct injury, with little change in the percentage of portal tracts with bile ducts (50–52%). None of the patients in the lamivudine study normalized alkaline phosphatase. Histological assessment following Combivir therapy revealed a 6 to 4 improvement in necroinflammatory score (p < 0.03, 95% CI: 0.53–2.33), a 3 to 1 reduction in bile duct injury (p < 0.02, 95% CI: 1.08–2.07), and a 45–75% increase in portal tracts with bile ducts (p < 0.05, 95% CI: 0.02–0.29). In the Combivir cohort, five patients normalized alkaline phosphatase and four developed normal AST, ALT, and alkaline phosphatase.
CONCLUSIONS:
Histological and biochemical endpoints were achieved in the Combivir pilot study suggesting a larger placebo-controlled trial is required as a proof of principle to assess whether antiviral therapy impacts the PBC disease process.
