Obesity, hepatic metabolism and disease

Nonalcoholic steatohepatitis (NASH), which is the most severe histological form of nonalcoholic fatty liver disease, is emerging as the most common clinically important form of liver disease in developed countries. Although its prevalence is 3% in the general population, this increases to 20-40% in obese patients. Since NASH is associated with obesity, its prevalence has been predicted to increase along with the growing epidemic of obesity and type 2 diabetes mellitus. The importance of this observation comes from the fact that NASH is a progressive fibrotic disease in which cirrhosis and liver-related death occur in 25 and 10% in these patients, respectively, over a 10-year period. This is of particular concern given the increasing recognition of NASH in the developing world. Treatment consists of treating obesity and its comorbidities: diabetes and hyperlipidemia. Nascent studies suggest that a number of pharmacological therapies may be effective, but all remain unproven at present. Histological and laboratory improvement occurs with a 10% decrease in bodyweight. Bariatric surgery is indicated in selected patients. A greater understanding of the pathophysiological progression of NASH in obese patients must be obtained in order to develop more focused and improved therapy.