Hepatitis C Virus HCV

HCV is a single-stranded RNA virus which shows marked genetic heterogeneity and at least six major subtypes are known, of which Ib is thought to be the most likely to lead to chronic liver disease. Whilst it is associated with only about one-sixth of all cases of hepatocellular carcinoma world-wide, this proportion is higher and rising in some areas, notably Japan and, to a lesser extent, Spain, Italy and the Middle East (Idilman et al., 1998; Bosch et al., 1999; Colombo, 1999). The infection is usually acquired in adult life via transfusion of blood and blood products or by the use of contaminated instruments and syringes by intravenous drug abusers. Perinatal and sexual transmission are unimportant. The onset of malignancy is preceded by cirrhosis in 90% of cases. The course is long, 20-40 years from infection to tumour, and patients are affected in late middle to old age. Table 3 shows that HCV is definitely associated with hepatocellular carcinoma in case-control and follow-up studies, but the pathogenesis is unknown. As it is an RNA virus, which does not possess a reverse transcriptase enzyme, it cannot integrate into the nuclei of liver cells. Instead, the risk of malignancy is associated with continued viral replication, liver cell death and stimulus to proliferation which lead to cirrhosis. However, hepatocellular carcinoma develops in a minority of cases without preceding cirrhosis and, therefore, a direct onco-genic effect cannot be ruled out. Accumulation of HCV core protein is thought to be the most likely mechanism. The co-existence of chronic HBV infection and alcoholism greatly increases the risk of malignancy. Attack rates of HCV infection have been reduced by screening of blood donors and the widespread use of disposable syringes but no vaccine is available and, because of the antigenic versatility of the virus, it may take many years yet to develop.

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