Currently, 170 million people worldwide are infected with HCV. The standard treatment is a combination therapy of interferon and ribavirin, which is only effective in about 55 percent of patients. The remaining 45 percent 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 mechan ism," 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."