Hepatocellular carcinoma in Japanese patients with nonalcoholic fatty liver disease, alcoholic liver disease, and chronic liver disease of unknown etiology: report of the nationwide survey

Abstract
To clarify the etiology of hepatocellular carcinoma (HCC) in Japanese patients with non-viral liver disease, we performed a nationwide survey. The influence of obesity, lifestyle-related diseases, and alcohol consumption was focused on. A nationwide survey of 14,530 HCC patients was conducted in 2009. Clinical features were studied for HCC patients with nonalcoholic fatty liver disease (NAFLD-HCC; n = 292), alcoholic liver disease (ALC-HCC; n = 991), and chronic liver disease of unknown etiology (unknown HCC; n = 614). The unknown HCC was divided into two subgroups, a no alcohol intake group and a modest alcohol intake group. ALC-HCC accounted for 7.2% of all HCC, followed by unknown HCC (5.1%) and NAFLD-HCC (2.0%). The characteristics of these three groups were clearly different (median age was 72 years for NAFLD-HCC, 68 years for ALC-HCC, and 73 years for unknown HCC, p < 0.01; female gender was 38, 4, and 37%, respectively, p < 0.01). Obesity and lifestyle-related diseases were significantly more frequent in NAFLD-HCC than in ALC-HCC and unknown HCC. The no alcohol intake subgroup of unknown HCC showed female predominance (58%) and was older, without a high prevalence of obesity and lifestyle-related diseases. In contrast, the modest alcohol intake subgroup showed the same trends regarding gender, body mass index, prevalence of lifestyle-related diseases, and liver function as the ALC-HCC group. The clinical features of ALC-HCC, NAFLD-HCC, and unknown HCC were clearly different. Modest intake of alcohol might have a more significant role in hepatic carcinogenesis than is presently thought.