Statin Boosts Response to Pegylated Interferon/Ribavirin

By Liz Highleyman

A number of studies -- both laboratory analyses and observation studies in which hepatitis C patients happened to be taking statins for other reasons -- have suggested that statins, also known as HMG-CoA reductase inhibitors, can inhibit hepatitis C virus (HCV) replication and therefore might be a useful addition to interferon-based therapy.

As reported at the European Association for the Study of the Liver's International Liver Congress (EASL 2011) this week in Berlin, Romanian researchers conducted a double-blind pilot study to assess the effects of fluvastatin -- the statin that appears to have the most potent anti-HCV activity -- on virological response to standard hepatitis C treatment.

The study included more than 200 previously untreated chronic hepatitis C patients with hard-to-treat HCV genotype 1. People who had taken statins within the year prior to the start of the study were excluded.

In addition to using a standard regimen of pegylated interferon plus ribavirin for 48 weeks, participants were randomly assigned to receive either a normal therapeutic dose of fluvastatin (20 mg once-daily) or placebo for 72 weeks -- that is, through the end of the 24 week post-treatment follow-up period for determining sustained virological response (SVR). The randomly chosen patients received the statin irrespective of their lipid profiles.

Results

	At week 12 of treatment, patients taking fluvastatin were significantly more likely to achieve early virological response (EVR) than placebo recipients, 76% vs 62%, respectively (odds ratio 1.94, or about twice as likely).
	The same effect was observed for SVR, with rates of 63% vs 49%, respectively (odds ratio 1.77).
	In an analysis that excluded participants with metabolic syndrome (about one-quarter of the study population), early and sustained response rates remained higher in the fluvastatin arm (EVR 85% vs 71%; SVR 74% vs 58%).
	Fluvastatin recipients experienced larger percentage decreases in HCV viral load.
	There were no significant differences, however, in ALT levels between the 2 arms.

"Fluvastatin showed a significant, albeit modest improvement in terms of EVR and SVR in chronic hepatitis C [patients] treated with standard [pegylated interferon/ribavirin] therapy," the investigators concluded.

"This synergistic effect with interferon, driven perhaps through the inhibition of geranylgeranylation of cellular proteins," they hypothesized, suggests that "lipid-lowering agents might favor HCV clearance and can be useful in chronic hepatitis C treatment, irrespective the presence of metabolic syndrome."

Investigator affiliations: Internal Medicine/Gastroenterology, Filantropia Municipal Hospital, Craiova, Romani;a Internal Medicine, University of Medicine and Pharmacy Craiova, Craiova, Romania Internal Medicine, Morphopathology, and Endocrinology, Filantropia Municipal Hospital, Craiova, Romania

4/1/11

Reference
EF Georgescu, L Streba, R Teodorescu, et al. Potential enhancement of both early (EVR) and sustained (SVR) virological response by fluvastatin in chronic hepatitis C treated with standard PegIFN-ribavirin therapy. A pilot study. 46th Annual Meeting of the European Association for the Study of the Liver (EASL 2011). Berlin. March 30-April 3. Abstract 198.