A role for the nucleotype in the pathogenesis of primary hepatocellular carcinoma

The risk of developing primary hepatocellular carcinoma (HCC) is 200 times higher for chronic carriers of hepatitis B virus antigen (HBsAg) than for the rest of the population. There is experimental evidence which suggests that the expression of viral DNA sequences integrated into the host's genome directly contributes to HCC development. However, most evidence available suggests that development of HCC requires a second genetic event that results from the chronic hepatitis and cirrhosis observed in symptomatic HBsAg chronic carriers. Here it is argued that the nucleotype, defined as those non-genic characters of nuclear DNA that affect or control the phenotype, is the element that links the viral, cellular and host factors involved in the genesis of HCC.