Diagnosing and treating hepatitis C virus infection.

Hepatitis C virus (HCV) infection is the leading cause of cirrhosis and liver transplantation in the United States. It is difficult to assess the prevalence of HCV infection; the asymptomatic nature of acute infection and early chronic infection leaves many infected individuals undiagnosed. Exposure to infected blood is the primary means for HCV transmission, with intravenous drug use the most common source. Genotype 1 HCV infection accounts for approximately 75% of cases. Because of the asymptomatic and slow course of HCV infection, many physicians and healthcare advocates support routine testing at the primary care level, especially in patients 40 to 65 years of age. Approximately 80% of individuals infected with HCV fail to clear the virus, although this varies considerably based on sex, age at infection, immune status, route of infection, race, alcohol use, and presence of steatosis. Long-term outcomes of chronic HCV infection are cirrhosis, end-stage liver disease, and hepatocellular carcinoma. The current standard of care for patients with chronic HCV infection is combination therapy with subcutaneous injections of peginterferon plus oral ribavirin for 48 weeks. A sustained virologic response (SVR) is also considered a virologic "cure." There is a trend toward response-guided therapy, in which treatment duration is shortened or lengthened based on viral genotype, patient characteristics, and viral kinetics. The efficacy and tolerability of peginterferon therapy, however, is limited. Approximately 45% of patients infected with HCV genotype 1 achieve an SVR, whereas 65% of those infected with gentoype 2 or 3 do so. Moreover, retreatment or switching to other interferons provides little benefit. Several new therapies for HCV infection are in development. Protease inhibitors are expected to become the new standard of care for nonresponders, with the potential to become a first-line treatment for chronic HCV infection.