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Pharmacotherapy of hepatitis C virus infection: a brief review.

Article Excerpt
Hepatitis C virus (HCV) is a viral pandemic, with an estimated 170 million persons infected worldwide. In the United States, over 3 million persons are infected, making it the most common blood borne infection in America (Armstrong et al., 2006; Wasley, Grytdal, & Gallagher, 2008).

HCV is an RNA virus that belongs to the flavivirus family. There are at least six different HCV genotypes (genotypes 1 to 6) and more than 50 subtypes. In the United States, HCV genotype 1 is the most common form. There is little difference in severity of disease or outcomes between genotypes. However, genotypes 2 and 3 are more likely to respond to interferon therapy than genotype 1. HCV infects hepatocytes, leading to liver disease. About 15% to 25% of persons infected will spontaneously clear infection without treatment; however, approximately 75% to 85% will remain chronically infected. Of those patients with chronic infection, 60% to 70% will develop chronic liver disease, 5% to 50% will go on to develop cirrhosis over the course of 20 to 30 years, and 1% to 5% will die from liver disease (cirrhosis or cancer). Other medical conditions, such as glomerulonephritis, essential mixed cryoglobulinemia, porphyria cutanea tarda, diabetes, and non-Hodgkins lymphoma, are more common in HCV-infected persons (National Digestive Diseases Information Clearinghouse, 2006).

Hepatitis C is usually diagnosed when serum aminotransferases are elevated and anti-HCV antibodies are found in the serum. The diagnosis is confirmed by detecting HCV RNA in the serum. A liver biopsy is not necessary for diagnosis, but may be useful in grading the severity of the disease and staging the degree of fibrosis. Chronic hepatitis C is defined as a positive anti-HCV antibody and elevated serum aminotransferases for more than 6 months (National Institutes of Health [NIH], 2002).

Treatment

The goal of therapy is to prevent complications associated with HCV infection, which can be achieved by eradicating the virus. Eradication of the virus is considered when there is a sustained virologic response (SVR) as defined by the absence of detectable HCV RNA at the end of treatment and 6 months later (see Table 1) (Strader, Wright, Thomas, & Seeff, 2004). The SVR is the most reliable endpoint for the evaluation of therapy, and has been associated with long-term beneficial clinical outcomes, such as improved quality of life, decrease in liver inflammation/fibrosis, and prevention of the development of hepatocellular carcinoma. There are currently two types of therapeutic modalities available: the immunomodulators (interferons) and ribavirin, an antiviral drug (see Table 2).

Interferons

Interferons are biological response modifiers that have antiviral, antiproliferative, and immunomodulatory effects. There are two types of interferon preparations approved for the treatment of chronic hepatitis C infection. The standard or non-pegylated interferons include...

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