Pathophysiology of non-alcoholic steatohepatitis and basis for treatment

Non-alcoholic fatty liver disease (NAFLD) is likely the most common cause of liver disease in adults as well as in children and adolescents. Its occurrence is closely associated with obesity and insulin resistance. NAFLD may lead to non-alcoholic steatohepatitis (NASH) with possible evolution towards cirrhosis and hepatocellular carcinoma. In addition to steatosis, NASH is characterized by necroinflammation and fibrosis. While the presence of simple steatosis can be assessed by imaging studies, the occurrence of NASH and its staging requires a liver biopsy. Along these lines, major efforts are directed at identifying non-invasive methodologies able to discriminate simple NAFLD from NASH and to predict the stage of fibrotic evolution. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and anti-inflammatory and antifibrogenic agents are under evaluation.