Reuters Health Information (2005-01-07): Primary biliary cirrhosis may respond to Combivir treatment
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.