Statins in the Treatment of Hepatitis C

Hepatitis C virus (HCV) infection is an important health issue because it affects about 3% of the world population. It is estimated that 65–80% of HCV infections progress to chronic disease, and more than 20–50% of patients with chronic hepatitis develop hepatic cirrhosis. Hepatocel-lular carcinoma complicates 5% of the chronic hepatitis C cases (1, 2). Combination therapy with peginterferon– ribavirin, which is currently the standard treatment for chronic hepatitis C, shows a sustained virological response in 55% of patients. The remaining 45% of patients do not respond to antiviral therapy and are at risk of the HCV infection progressing to hepatic cirrhosis and hepa-tocellular carcinoma (3). In addition, because of the numerous adverse effects and possible contraindications to the use of combination therapy with peginterferon and ribavirin, the administration of this antiviral therapy is limited to only some patients with chronic hepatitis C (4). Because of these limitations, it is necessary to discover new therapeutic agents for eradicating HCV infection. Several recent studies have shown that statins, commonly used as cholesterol-lowering medication, can inhibit the replication of HCV (3, 5, 6). Ikeda et al. (2) have reported in their 2006 study that statins can inhibit in vitro HCV replication. Using OR6 cells infected with HCV, the authors evaluated the antiviral activity of 5 statins: atorvastatin, fluvastatin, lovastatin, pravastatin, and sim-vastatin. All statins, except pravastatin, that were tested as monotherapy inhibited viral replication. Fluvastatin exhibited the strongest antiviral effect, whereas atorv-astatin and simvastatin showed moderate inhibitory effects , and lovastatin exhibited a weak inhibitory effect on HCV replication. All of these statins exert a cholesterol lowering effect by inhibiting the activity of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, an enzyme involved in cholesterol synthesis. Pravastatin, unlike the other tested statins, has no antiviral activity; hence, it inhibits HCV replication not by a direct action on HMG-CoA reductase, but by a specific antiviral mechanism (3). In order to emphasize the presence of an existing antiviral mechanism, the authors showed that the antiviral activity of statins is not due to hepatotoxicity; they proved so by demonstrating that HCV replication is not inhibited by the destruction of hepatocytes (3). Several in vivo studies have shown that the administration of statins in patients with chronic HCV infection is safe and has no severe adverse effects (7-9). For its replication, HCV requires a number of proteins, which are involved in cholesterol synthesis. Statins are considered to exert …