Clinical

Primary biliary cirrhosis may respond to Combivir treatment

Last Updated: 2005-01-07 15:15:22 -0400 (Reuters Health)

NEW YORK (Reuters Health) - The inflammation, bile duct injury and ductopenia associated with the autoimmune disorder primary biliary cirrhosis (PBC) may respond to treatment with the antiretroviral agent Combivir (zidovudine/lamivudine, GlaxoSmithKline), results of a pilot study suggest.

Lead investigator Dr. Andrew L. Mason and colleagues previously reported that PBC is associated with infection by human betaretrovirus (see Reuters Health report, June 23, 2003.)

In the current report, published in the December issue of the American Journal of Gastroenterology, Dr. Mason, a hepatologist currently based at the University of Alberta in Edmonton, Canada, and his team first studied a cohort of 11 patients treated with lamivudine only (150 mg/day).

After 1 year, however, they observed either no improvement or progression in necroinflammatory scores, bile duct injury and fibrosis. There were also no significant biochemical changes.

A second cohort of 11 patients (including 7 patients from the first trial) received lamivudine 150 mg and zidovudine 300 mg (Combivir) b.i.d. After 1 year, the subjects exhibited improvements in necroinflammatory scores (p < 0.03), bile duct injury scores (p < 0.02), and portal tracts with demonstrable bile ducts (p < 0.05).

All patients in the Combivir group also had significant improvements or normalization of serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase by 6 months.

"We believe that this antiviral study provides additional support for a retroviral involvement in the pathogenesis of PBC and offers some reassurance that 1-year treatment is relatively safe," the authors conclude. They note that a multicenter, placebo-controlled study of combination antiviral therapy is currently underway.

In a related editorial, Dr. M. Eric Gershwin of University of California at Davis and Dr. Carlo Selmi at the University of Milan in Italy suggest that Dr. Mason's group has put "the cart before the horse," by failing to provide more evidence that retroviral infection is the cause of PBC.

"None of us knows what causes PBC and we all depend on evidence-based research with the use of rigorous controls to ascertain this critical question," they write. They believe that clinical trials of antiretroviral drugs are premature and should await further delineation of the mechanisms involved in PBC.

Am J Gastroenterol 2004;99:2348-2358.