Fluvastatin Inhibits Hepatitis C Replication in Humans

April 15, 2008

The American Journal of Gastroenterology

OnlineEarly Articles

To cite this article: Ted Bader M.D., Javid Fazili M.D., Mohammed Madhoun M.D.,

Aston Ph.D., Diane N.P., Syed Rizvi M.D., Ken Seres M.D.,

Muhammad Hasan M.D. (2008)

Fluvastatin Inhibits Hepatitis C Replication in Humans

doi:10.1111/j.1572-0241.2008.01876.x

Abstract

ORIGINAL CONTRIBUTIONS

Fluvastatin Inhibits Hepatitis C Replication in Humans

Ted Bader, M.D.1,21Veteran's Administration Medical Center2University of

Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, Javid Fazili,

M.D.1,21Veteran's Administration Medical Center2University of Oklahoma Health

Sciences Center, Oklahoma City, Oklahoma, Mohammed Madhoun, M.D.1,21Veteran's

Administration Medical Center2University of Oklahoma Health Sciences Center,

Oklahoma City, Oklahoma, Aston, Ph.D.22University of Oklahoma Health

Sciences Center, Oklahoma City, Oklahoma, Diane , N.P.11Veteran's

Administration Medical Center, Syed Rizvi, M.D.1,21Veteran's Administration

Medical Center2University of Oklahoma Health Sciences Center, Oklahoma City,

Oklahoma, Ken Seres, M.D.1,21Veteran's Administration Medical Center2University

of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, and Muhammad Hasan,

M.D.1,21Veteran's Administration Medical Center2University of Oklahoma Health

Sciences Center, Oklahoma City, Oklahoma1Veteran's Administration Medical

Center, and 2University of Oklahoma Health Sciences Center, Oklahoma City,

Oklahoma

Approved by the University of Oklahoma Health Sciences IRB Committee on

September 7, 2006, study #13305; FDA IND license number 75605, issued on August

2, 2006.

Reprint requests and correspondence: Ted Bader, M.D., 111H, GI Section, VA

Medical Center, 921 NE 13th St., Oklahoma City, OK 73104.

(Am J Gastroenterol 2008;103:1–7)

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 log10 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.

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1572-0241.2008.01876.x

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April 15, 2008