Pilot Studies of Single and Combination Antiretroviral Therapy in Patients with Primary Biliary Cirrhosis
| Autor: | Andrew Mason, Lizhe Xu, Stefan G. Hubscher, Gist Farr, James Neuberger |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male medicine.medical_specialty medicine.medical_treatment Pilot Projects Gastroenterology Zidovudine Primary biliary cirrhosis Liver Function Tests Acquired immunodeficiency syndrome (AIDS) Internal medicine Immunopathology medicine Humans Sida Aged Analysis of Variance Chemotherapy Hepatology biology medicine.diagnostic_test Liver Cirrhosis Biliary business.industry Lamivudine Middle Aged medicine.disease biology.organism_classification Surgery Drug Combinations Treatment Outcome Liver Reverse Transcriptase Inhibitors Female Liver function tests business Retroviridae Infections medicine.drug |
| Zdroj: | The American Journal of Gastroenterology. 99:2348-2355 |
| ISSN: | 1572-0241 0002-9270 |
| DOI: | 10.1111/j.1572-0241.2004.40741.x |
| Popis: | 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.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 Eleven PBC patients enrolled in each study, seven patients were entered into both studies, and one patient was withdrawn from each study due to side effects.Evaluation of liver biopsies before and after lamivudine therapy showed a 4-5 increase in necroinflammatory score, a 1-1.5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 (p0.03, 95% CI: 0.53-2.33), a 3 to 1 reduction in bile duct injury (p0.02, 95% CI: 1.08-2.07), and a 45-75% increase in portal tracts with bile ducts (p0.05, 95% CI: 0.02-0.29). In the Combivir cohort, five patients normalized alkaline phosphatase and four developed normal AST, ALT, and alkaline phosphatase.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. |
| Databáze: | OpenAIRE |
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