Statins May Increase Antiviral Activity of Hepatitis C Therapies and Delay Development of Resistance

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Statin drugs, typically used to manage high cholesterol, reduced hepatitis C virus (HCV) replication and increased the activity of interferon and directly-targeted anti-HCV agents in laboratory studies, and prevented development of resistance, according to a report in the July 2009 issue of Hepatology.

Statins, or 3-hydroxyl-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, have previously been shown to inhibit HCV replication in vitro and in small human studies.

As described in the present report, a Belgian/French research team found that among the 5 statins studied, mevastatin (not approved) and simvastatin (Zocor) exhibited the strongest in vitro anti-HCV activity in replicons models. Lovastatin (Mevacor) and fluvastatin (Lescol) had moderate antiviral activity, and pravastatin (Pravachol) was "devoid of an antiviral effect."

These results differ somewhat from those of an earlier Japanese study, which found that fluvastatin had the strongest effect, followed by simvastatin and atorvastatin (Lipitor, not included in the present analysis).

When they combined statins with interferon-alfa or directly targeted HCV polymerase and protease inhibitors, the researchers observed additive antiviral activity in 3-day assays. While neither statins (at 5 times their 50% effective concentration [EC50] value) nor any of the tested anti-HCV agents (at 10 to 20 times their EC50 values) were able to clear HCV replicons from cell cultures, a combination of HCV polymerase or protease inhibitors plus mevastatin or simvastatin resulted in efficient clearance.

In colony formation experiments, the investigators found that mevastatin either reduced the frequency or prevented the selection of HCV replicons with resistance to the non-nucleoside polymerase inhibitor HCV-796 (no longer in development).

Base on these findings, the researchers concluded, "A combination of specific HCV inhibitors with statins may result in a more profound antiviral effect and may delay or prevent the development of resistance to such inhibitors."

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium; INSERM, U871, Lyon, France; Université Lyon 1, Lyon, France; Hospices Civils de Lyon, Hôtel Dieu, Service d'hépatologie et de gastroentérologie, Lyon, France; Virology Unit, Laboratory of Epigenetic of Cancer, Faculty of Medicine, ULB, Belgium.

8/11/09

Reference

L Delang, J Paeshuyse, I Vliegen, and others. Statins potentiate the in vitro anti-hepatitis C virus activity of selective hepatitis C virus inhibitors and delay or prevent resistance development. Hepatology 50(1): 6-16. July 2009. (Abstract).