Hepatitis C virus infection (HCV) is a major cause of cirrhosis and death from liver disease
worldwide. Current therapy for HCV with interferon based therapies results in cure rates of
around 5055% which leaves a significant number of patients without effective therapy. HCV
induces (can bring on) insulin resistance and insulin resistance is a factor known to reduce
the response to antiHCV therapy. This finding stimulated initial studies looking at agents
that may reduce insulin resistance as additional therapy in HCV infection.
A study using metformin in addition to interferon and ribavirin showed a nonsignificant
increase in cure rates (53% vs. 42%), but this was limited to patients with type 1 infection
AND demonstrable insulin resistance. The assumption was made that the potential effect of
metformin was likely to be on insulin resistance and thus by modulating this enhances
response. The investigators (Prof M Harris, University of Leeds) have data (currently
unpublished)suggesting that metformin may have an antiviral effect independent of its effect
on insulin resistance, thus raising the possibility that metformin may have a direct
antiviral effect in vivo. Given that the development of specific antiHCV agents which target
viral proteins such as its polymerase and protease are in trial development but have so far
proved either highly toxic or are likely to have a huge cost there is considerable rationale
for looking at alternative potential antiHCV agents and in this context metformin is cheap,
readily available and has an excellent safety profile. This pilot study therefore addresses
the question "Does metformin therapy result in a significant drop in HCV viral load in
chronically infected patients?"