An Unbiased Approach to Discover Novel Therapies for Liver Disease

Alcoholic liver disease (ALD) represents a range of clinical and morphological changes that range from steatosis to inflammation and necrosis (alcoholic hepatitis) to progressive fibrosis (alcoholic cirrhosis) [1]. Most chronic heavy drinkers exhibit steatosis characterized by greater amount of macrovesicular fat content than microvesicular fat. In addition hepatocyte ballooning degeneration with mixed lobular inflammation is evident [2,3]. Patients with ALD also have elevated serum concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which are evidence of liver injury. The severity of disease is not always correlated with the amount of alcohol consumed. In fact, most long-term heavy drinkers develop steatosis, but only 20-30 % of these patients develop hepatitis, and less than 10 % will progress to cirrhosis [4-6]. Nonalcoholic fatty liver disease (NAFLD) can progress from steatosis to inflammation called nonalcoholic steatohepatitis (NASH