Mouse Model of Alcoholic Steatohepatitis

Alcoholic liver disease (ALD) is one of the most common causes of chronic liver disease in Western countries. The spectrum of ALD ranges from simple steatosis to steatohepatitis to cirrhosis and hepatocellular carcinoma. Over the past 50 years, several animal models of ALD have been developed. Although none of them faithfully recapitulates the human disease, they have proven to be invaluable tools to study the pathogenesis of ALD, to identify potential therapeutic targets and to test new drugs. Here, we describe the mouse model of chronic and binge ethanol feeding, also known as the NIAAA model or Gao binge model. This model combines chronic feeding of Lieber-DeCarli ethanol liquid diet with acute administration of high-dose ethanol by oral gavage to mimic the drinking patterns of many alcoholic patients who engage in episodes of binge drinking on top of chronic daily drinking. Short-term (10-day) chronic plus single binge ethanol feeding causes a substantial increase in serum transaminase levels, moderate steatosis and mild inflammation characterized by lobular neutrophil infiltration. Long-term (8-week) chronic plus single or multiple (twice a week) binge ethanol feeding induce more severe steatohepatitis and mild fibrosis. This clinically relevant, easy-to-perform model of ALD is currently used by many research laboratories to reproduce early stages of human alcoholic steatohepatitis.