Present and future therapeutic strategies in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is found in individuals who do not drink or abuse alcohol and represents a significant health burden for the general community. NAFLD is often associated with one or more features of the metabolic syndrome and has potential for evolution towards non-alcoholic steatohepatitis (NASH), the necro-inflammatory form of liver steatosis. The most worrisome evolutive events in a subgroup of NASH patients include advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. Pathophysiology of NAFLD/NASH is complex, but studies point to a pre-eminent role of oxidative stress and lipid peroxidation in the liver, including early mitochondrial dysfunction. Changes follow an insulin resistance status with a background of a chronic pro-inflammatory status due to an excess of visceral adiposity. Although no established therapy exists for NAFLD/NASH, potential therapeutic approaches are discussed in this review.