The Insights of Nonalcoholic Steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a form of fatty liver disease where benign hepatic steatosis leads to chronic inflammation in the steatotic liver of a patient without any history of alcohol abuse. NASH is a necro-inflammatory response that ensues when hepatocytes are injured by lipids (lipotoxicity). NASH is strongly associated with obesity and the metabolic syndrome, conditions that cause lipid accumulation in hepatocytes (hepatic steatosis). NASH is characterized by the presence of steatosis (the accumulation of fat in 5% or more of hepatocytes), hepatocellular ballooning, and inflammation. In NASH, lipotoxic hepatocytes result in the production of factors that promote wound healing as an attempt to replace dying hepatocytes. The presence of chronic and/or aberrant inflammation can lead to scar tissue deposition and the development of fibrosis and hepatocellular carcinoma Although clinical trials show promising results, there is actually no pharmacological agent approved to treat NASH. The rapidly increasing prevalence of this disease and of its aggressive form NASH will require novel therapeutic approaches based on a profound understanding of its pathogenesis to halt disease progression to advanced fibrosis or cirrhosis and cancer.This review emphases on our understanding of the epidemiology and pathogenesis of nonalcoholic steatohepatitis, which reinforces practice guidelines and drug development for this life-threatening liver disease.