Spontaneous development of hepatocellular carcinomas in the FLS mice with hereditary fatty liver.

The fatty liver Shionogi (FLS) mouse is an inbred strain that develops spontaneous fatty liver (hepatic steatosis) chronically without obesity. Here, we reported that the mice develop spontaneous hepatocellular tumors with high incidences. The mice with age of over 1 year frequently developed whitish protuberant nodules in the livers, which were histologically diagnosed as hepatocellular adenoma and/or carcinoma (HCC). An incidence of HCC was 12/30 (40%) in males at 15-16 months of age, while in females that was 0/36 at 13-16 months and 4/42 (9.5%) at 20-24 months. Furthermore, histological examinations showed that after 2-4 months of age mononuclear cell infiltration and clusters of foamy cells appear in the fatty liver with elevated serum alanine aminotransferase, suggesting presence of inflammatory responses and liver injury. These observations show that the FLS mice develop hepatocellular tumors following steatohepatitis. The mouse might be a good animal model for investigating liver tumor and non-alcoholic steatohepatitis.