An overview of nonalcoholic steatohepatitis: past, present and future directions.

Nonalcoholic steatohepatitis (NASH) emerged from an anecdotal disease first described in 1981 to the most common cause of incident chronic liver disease at the end of the current decade. This article describes, from a historical perspective, some of the landmark changes in our perception and understanding of this disease. Natural history studies have shown the potential for serious liver damage and ultimately increased overall and liver-related mortality. The recognition of insulin resitance as an almost universal underlying condition in patients with NASH, its role as a major determinant of steatogenesis and possibly liver disease progression contributed to the identification of a probable cause for this disease, one that is amenable to therapeutic intervention. Consequently, screening for liver injury in patients with metabolic risk factors entered clinical practice in hepatology and endocrine diseases. NASH can coexist with other frequent liver diseases and often aggravate the course of liver injury; therefore it should be seen as an independent disease and not as an entity diagnosed only by exclusion of other hepatopathies. Finally, steatosis can have systemic consequences as it worsens insulin resistance, predicts the emergence of metabolic complications and increases the risk for cardiovascular events. Priorities for future research are the optimisation of non-invasive screening strategies, the identification of patients at risk of liver disease progression, the understanding of the hepatic carcinogenic potential and testing innovative pharmacological targets for therapy.