Fluvastatin inhibits hepatitis C replication in humans

被引:169
作者
Bader, Ted [1 ,2 ]
Fazili, Javid [1 ,2 ]
Madhoun, Mohammed [1 ,2 ]
Aston, Christopher [2 ]
Hughes, Diane [1 ]
Rizvi, Syed [1 ,2 ]
Seres, Ken [1 ,2 ]
Hasan, Muhammad [1 ,2 ]
机构
[1] Vet Adm Med Ctr, GI Sect, Oklahoma City, OK 73104 USA
[2] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA
关键词
D O I
10.1111/j.1572-0241.2008.01876.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
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页码:1383 / 1389
页数:7
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