Clinical features of hepatocellular carcinoma associated with nonalcoholic fatty liver disease: a review of human studies.

Most cases of hepatocellular carcinoma (HCC) in Japan develop in the background of chronic liver disease caused by hepatitis C virus (HCV). Recently, however, HCV-associated HCC has been shown to be decreasing, while non-B and non-C HCC (NBNC-HCC), which is negative for HCV and hepatitis B virus infection, has increased. The main cause of NBNC-HCC is alcoholic liver disease, but the recent increase of NBNC-HCC is thought to be due to an increase in patients with nonalcoholic fatty liver disease (NAFLD). Approximately 10% of NAFLD cases involve nonalcoholic steatohepatitis (NASH), and NASH can progress to liver cirrhosis and its associated complications such as HCC. There are no accurate data on the percentage of NASH-related HCC among all-cause HCC in Japan, because no large-scale investigation has been performed. However, the rate is thought to be about 3% of overall HCC, which is lower than that in the United States. The incidence of HCC in patients with NASH-related cirrhosis is thought to be 2% per year, which is lower than that in HCV-related cirrhosis. Risks for NASH-related HCC include advanced hepatic fibrosis, older age, and being male. NAFLD that includes NASH is associated with metabolic syndrome, which includes obesity and diabetes, and metabolic syndrome is a risk factor for HCC. Genetic factors and dietary patterns may also be related to NASH-related HCC. Thus, regular HCC surveillance, as performed for patients with viral chronic liver disease, is required for patients with NAFLD, and diagnostic markers are required for simple, rapid and specific detection of NASH-related HCC.