ABSTRACT
HCC is associated with HCV and hepatitis B virus (HBV) infection in approximately 80% of cases. Most of the remaining cases in the West are related to other causes leading to liver cirrhosis, such as heavy alcohol intake, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, and metabolic liver diseases (e.g. hereditary hemochromatosis, Wilson's disease, hereditary tyrosinemia, type I glycogen storage disease, and α 1 -antitrypsin deficiency). Recently, non-alcoholic steatohepatitis-related cirrhosis has been recognized as an emerging problem. Indeed, cirrhosis is the strongest predisposing factor for HCC and, globally, 80-90% of HCC cases arise in severely fibrotic or cirrhotic livers. However, tumorigenesis of HCC probably differs between HBV infection versus other causes; HBV integrates its viral genome into the human host DNA, thus promoting malignant cell transformation regardless of the severity the liver parenchyma damage, whereas other causes, such as HCV and alcohol, induce cirrhosis, characterized by chronic necroinflammation which in turn can induce genomic mutations and eventually malignant cellular transformation. In Europe and the US, in patients with HCV-related cirrhosis, the incidence and 5-year cumulative risk for HCC are 3.7 cases per 100 person-years and 17%, respectively. In patients with HBVrelated cirrhosis, the incidence and 5-year cumulative risk for HCC are 2.2 cases per 100 person-years and 10%, respectively.
