Hepatitis C Genotypes: The Key to Pathogenicity?

Although investigation of the hepatitis C virus (HCV) has proceeded rapidly since the virus was discovered, numerous important issues about HCV, including the risk for disease progression in patients with chronic HCV infection and the role of interferon therapy, require clarification. This discussion focuses on predictors of both disease progression and response to interferon therapy; in particular, it considers the ways in which new research on HCV genotypes may shed light on these important and unresolved questions.

As it would for any chronic disease, an understanding of the natural history of HCV provides a basis for rational decisions about management of patients. Early studies of transfusion-associated hepatitis identified chronicity and histologic progression as prominent features of what was subsequently identified as HCV infection [1]. Before HCV was identified, prospective studies of hepatitis in transfusion recipients found that at least half of these recipients had elevated serum aminotransferase levels that persisted for more than 6 months after the first evidence of hepatic dysfunction, implying that the hepatitis had become chronic. Liver biopsy specimens in many of these affected persons subsequently documented histologically severe injury, including chronic active hepatitis and cirrhosis [1]. There has been some debate, however, about whether such findings actually translate into increased morbidity and mortality for the individual patient [2, 3].

The frequency of HCV infection in patients presenting to liver transplantation programs and the increasingly obvious association between cirrhosis and hepatocellular carcinoma [4] indicate that HCV can indeed be linked to clinically significant disease. The failure of some studies to detect adverse consequences in patients with chronic HCV infection probably reflects the indolent natural history of …