[Nonalcoholic fatty liver disease: 30 years research changed NASH]

Since the first description of nonalcoholic steatohepatitis (NASH) in 1980, much progress has been made towards its individualisation as a liver disease with potentially serious consequences. The identification of insulin resistance as a major determinant of steatogenesis and possibly of liver disease progression helped to identify a cause of this condition, which was amenable to therapeutic intervention and prompted screening for liver injury in patients with metabolic risk factors. The demonstration that steatohepatitis can coexist with other liver diseases with a detrimental effect on liver fibrosis helped this condition to be recognized as an independent hepatic disease no longer depending on exclusion of other chronic liver conditions. The robust increase in liver-related mortality, the fact that cirrhosis is a frequent and independent cause of death, as well as the significant decrease in overall mortality clearly showed the potential for severity of steatohepatitis. The data showing that steatohepatitis worsens insulin resistance and increases the risk for cardiovascular events and mortality forged the concept of extrahepatic complications of fat. Future research should focus on devising non-invasive strategies for screening of patients at risk, on understanding the natural history and risk factors of cirrhosis and hepatic carcinogenesis, and on optimizing therapeutic strategies integrating diet and lifestyle changes with targeted pharmacological agents.