Most acute infections are asymptomatic, fewer than 30% of acute infections have nonspecific symptoms and some develop mild jaundice. Fulminant hepatitis has been described but is uncommon. Extrahepatic manifestations include mixed cryoglobulinaemia, membraneous prolif-erative glomerulonephritis and porphyria cutanea tarda.
Between 50 and 80% of patients do not clear the virus by 6 months and develop chronic hepatitis. The rate of progression of chronic hepatitis is highly variable. Chronic hepatitis C infection leads to cirrhosis within two decades of the onset of infection in at least 20% of patients. Chronic infection is also associated with an increased risk of hepatocellular carcinoma, which occurs on a background of inflammation and regeneration related to chronic hepatitis over three or more decades. The risk of developing hepatocellular carcinoma is estimated at 1-5% after 20 years, but this varies considerably in different areas of the world. Hepatocellular carcinoma develops more commonly in men than in women.
Current routine diagnostic tests for detection of antibodies to HCV are sensitive and specific and most screening tests are based on enzyme immunoassays, with confirmatory tests based mainly on recombinant immunoblot assays. The presence of antibodies to specific antigenic components of HCV is variable and may or may not reflect viraemia. Detection and monitoring of viraemia are important for management and treatment and sensitive molecular techniques are available for the measurement of HCV RNA.
The identification of specific genotypes is important, with observations suggesting an association between response to antiviral treatment with interferon and particular genotypes.
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