Pilot studies of single and combination antiretroviral therapy in patients with primary biliary cirrhosis.
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 Eleven PBC patients enrolled in each study, seven patients were entered into both studies, and one patient was withdrawn from each study due to side effects.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.
Mason
Andrew L
AL
Section of Gastroenterology and Hepatology, Ochsner Clinic Foundation, New Orleans, Louisiana, USA.
Farr
Gist H
GH
Xu
Lizhe
L
Hubscher
Stefan G
SG
Neuberger
James M
JM
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D004338:Drug Combinations; D005260:Female; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000821:virology; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000821:virology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012192:Retroviridae Infections / Q000150:complications / Q000188:drug therapy; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D015215:Zidovudine / Q000627:therapeutic use*
D004338:Drug Combinations; D018894:Reverse Transcriptase Inhibitors; C109078:lamivudine, zidovudine drug combination; D019259:Lamivudine; D015215:Zidovudine