There is evidence that 50-80% or more of infections with HCV progress to chronic liver disease. Histological examination of liver biopsies from asymptomatic 'healthy' blood donor carriers of HCV show that none has normal liver histology and up to 70% have chronic active hepatitis and/or early cirrhosis. Histological changes at the time of the first biopsy in patients with biochemical chronic hepatitis C also show chronic active hepatitis in the majority. Characteristic histological changes include heavy lymphocytic infiltration in the portal and periportal areas. Progression to cirrhosis is common, and in a number of countries such as Japan, progression to hepatocellular carcinoma is an important feature of chronic hepatitis C. The mechanism underlying carcinogenesis is likely to be associated with the process of fibrosis and regeneration of liver cells, as there is no DNA intermediate in the replication cycle of HCV or integration of viral nucleic acid.

Whether the virus is cytopathic or whether there is an immunopathological element remains unclear, but a combination of factors including gender, excessive alcohol intake and coexisting viral disease (particularly hepatitis B) are important interactive factors.

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