The impact of obesity on liver histology.

Obesity and insulin resistance produce alterations in the liver's normal role in lipid metabolism resulting in a sequence of changes recognizable on liver biopsy. Hepatocellular fat vacuoles increase with BMI, producing steatosis. Steatohepatitis occurs when there is also cytoskeletal damage with loss of keratin filaments, ballooning of affected liver cells and formation of Mallory-Denk bodies. Activation of hepatic stellate cells produces fibrosis in the perisinusoidal spaces. With continuing fibrogenesis there is progression to bridging fibrosis and cirrhosis. Hepatocellular carcinoma may develop in the cirrhotic liver, but both hepatocellular adenoma and hepatocellular carcinoma may occur in pre-cirrhotic fatty liver disease.