Hepatitis C: natural history, diagnosis, and management.

The virology, epidemiology, clinical spectrum, diagnosis, and management of hepatitis C are reviewed. Hepatitis C infection is responsible for most cases of chronic viral hepatitis in the United States and is the major reason for liver transplantation. Hepatitis C virus (HCV) is divided into six major genotypes, with type 1 being the most prevalent in the United States. Direct percutaneous exposure is the main route of HCV transmission. Diagnosis of the infection is made by HCV antibody testing or direct detection of HCV RNA in serum. Liver biopsy is recommended for evaluating disease severity before treatment is started. The currently approved treatment for patients with chronic hepatitis C who have elevated liver transaminases and compensated liver disease consists of interferon alfa alone or in combination with ribavirin. Rates of sustained biochemical and virological responses in the range of 20-40% have been reported for a 12-month regimen of interferon alfa. Combination therapy with ribavirin improves these rates. Response rates are lower in patients with HCV genotype 1, a serum HCV RNA concentration higher than 1 million copies/mL, and cirrhosis. In patients who relapse after an initial response to interferon alfa, retreatment with interferon alfa plus ribavirin or with a higher dosage of interferon alfa is recommended. New agents under development for use against hepatitis C include viral enzyme inhibitors, ribozymes and antisense oligonucleotides, and immunomodulators. Further research is needed to optimize existing strategies for treating hepatitis C and to develop new, more effective therapies. Ultimately, combination therapies may hold the key.