Fluvastatin inhibits hepatitis C replication in humans

Am J Gastroenterol. 2008 Jun;103(6):1383-9. doi: 10.1111/j.1572-0241.2008.01876.x. Epub 2008 Apr 14.

Abstract

BACKGROUND Hepatitis C viral (HCV) infection is the leading cause of death due to liver disease in the United States. Currently, pegylated interferon and ribavirin produce sustained viral remission in only 50% of patients. Additional agents are needed to increase the cure rate. In vitro experiments show strong antiviral effects of fluvastatin against HCV.

Objectives: To assess the safety and antiviral effects of fluvastatin in chronic HCV carriers.

Methods: 31 veterans with chronic HCV were prospectively given oral doses of fluvastatin, 20 to 320 mg/day, for 2-12 weeks with weekly monitoring of HCV RNA and liver tests. Reductions of viral load (P < 0.01) versus a control group were considered suppressive.

Results: With 80 mg a day or less, 11/22 (50%) patients responded by lowering HCV RNA. The first lowering occurred within 4 weeks (9/11, 82%). The greatest weekly change in HCV RNA level was a 1.75 log(10) reduction. When lowered in responders, the viral load remained relatively constant for 2-5 weeks (7/9, 78%), or on the next test rebounded immediately to a non-significant change from, baseline (n = 2). Continued lowering of virus was seen in 2/19 (22 %) patients when the study ended. We found no evidence of liver tests worsening.

Conclusions: FLV used as monotherapy in vivo showed suppressive effects of HCV clinically that are modest, variable, and often short-lived. These findings support "proof-of-concept" for pilot trials combining fluvastatin with standard therapy. Statins and fluvastatin, in particular, appear to be safe for use in hepatitis C.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Fatty Acids, Monounsaturated / administration & dosage*
  • Fatty Acids, Monounsaturated / adverse effects
  • Female
  • Fluvastatin
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Indoles / administration & dosage*
  • Indoles / adverse effects
  • Liver Function Tests
  • Male
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome
  • Viral Load

Substances

  • Fatty Acids, Monounsaturated
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indoles
  • Fluvastatin