Hepatocellular carcinoma in non-alcoholic steatohepatitis: Growing evidence of an epidemic?

The incidence of hepatocellular carcinoma in non-viral-related chronic liver disease has gradually increased in Japan. Obesity and diabetes mellitus type 2 have been established as a significant risk factor for hepatocellular carcinoma (HCC) by epidemiologic observations and experimental studies. The risks of these factors for HCC are likely conferred by two factors: the increased risk for development of non-alcoholic steatohepatitis (NASH) and the carcinogenic potential of themselves. Hepatocellular carcinoma in NASH is difficult to evaluate because histological diagnosis is required for diagnosis of NASH, which can lead selection bias. Furthermore, end-stage NASH is in effect "burned-out" NASH, for which the diagnosis of NASH cannot be made any more. At all events, previous studies on the etiology of Japanese HCC showed that non-alcoholic fatty liver disease accounts for 1-5% of all HCC (male predominant, median age 72 years). They have high prevalences of obesity and/or diabetes mellitus type 2 and 10-75% of the HCC arose from non-cirrhotic livers. HCC in NASH may be of multicentric origin, similar to HCC based on viral hepatitis. Regular screening for HCC is extremely important especially in cirrhotic NASH patients and recurrence should be warned. In western and Asian countries, the prevalence of non-alcoholic fatty liver disease in the general population is increasing dramatically. Therefore, there is an urgent need to elucidate pathogenesis and clinical features of HCC in NASH. In this review we summarize current concepts for HCC in NASH.