Public release date: 6-Jul-2006

Statins stop hepatitis C virus from replicating

A new study shows that statins, which are typically used as anti-cholesterol
medications, can inhibit the replication of the hepatitis C virus (HCV).
They could replace ribavirin in combination therapy with interferon. These
findings are published in the July 2006 issue of Hepatology, the official
journal of the American Association for the Study of Liver Diseases (AASLD).
Published by John Wiley & Sons, Inc., Hepatology is available online via
Wiley InterScience at http://www.interscience.wiley.com/journal/hepatology.

Many tinfected with HCV face a threat of the disease progressing to
cirrhosis and liver cancer. Based on recent reports that one statin,
lovastatin, inhibits HCV replication, researchers led by Masanori Ikeda of
Okayama University in Japan, tested other statins in search of a more
effective anti-HCV therapy.

Using the OR6 cell culture assay system, they evaluated the anti-HCV
activities of five statins: atorvastatin, fluvastatin, lovastatin,
pravastatin and simvastatin. When the statins were tested alone, all except
pravastatin inhibited HCV replication. Fluvastatin had the strongest effect.
Atorvastatin and simvastatin had moderate effects while lovastatin had a
weak effect. While pravastatin exhibited no anti-HCV activity, it did work
as an inhibitor for HMG-CoA reductase, suggesting that the anti-HCV
activities of the other stains are not due to the direct inhibition of
HMG-CoA.

The researchers determined that the anti-HCV activities of statins were not
related to cytotoxicity, meaning they did not kill the host cell. Additional
experiments also suggested that, "the statins possess the ability to inhibit
the replication of HCV RNA via a specific antiviral mechanism," the authors
report.

The researchers tested the theory that certain proteins are required for HCV
RNA replication and that statins block the replication by inhibiting those
proteins. In support of this theory, they found that the addition of both
mevalonate and geranylgeraniol restored HCV RNA replication in the
statin-treated cells.

To evaluate statins as potential replacements for ribavirin in combination
therapy, the researchers tested the anti-HCV activities of each one when
combined with interferon. Each combination, except the one including
pravastatin, had even stronger inhibitory effects on HCV RNA replication
than when the statin was used alone. Again, fluvastatin plus interferon
exhibited the strongest effect. "We clearly demonstrated that co-treatment
of interferon and fluvastatin was an overwhelmingly effective treatment,"
the authors report. This combined therapy was more effective against HCV RNA
replication than interferon alone and more effective than the standard
combination therapy of interferon and ribavirin.

"Statins are good reagents for combination therapy with interferon in
patients with chronic hepatitis C," the authors conclude. "Furthermore, our
developed OR6 assay system will be useful for the time-saving screening of
new anti-HCV reagents."

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Article: "Different Anti-HCV Profiles of Statins and Their Potential for
Combination Therapy with Interferon," Masanori Ikeda, Ken-ichi Abe, Masashi
Yamada, Hiromichi Dansako, Kazuhito Naka, Nobuyuki Kato, Hepatology; July
2006; (DOI: 10.1002/hep.21232).