Nonalcoholic fatty liver disease: a review of current understanding and future impact.

Nonalcoholic fatty liver disease (NAFLD), already the most common form of liver disease in the United States, can be expected to increase in prevalence and severity in parallel with national epidemics of obesity and type 2 diabetes. NAFLD is frequently associated with insulin resistance. While insulin resistance, and thereby hyperinsulinemia, are, in large part, metabolic consequences of obesity, the basis of diversity in severity and progression of inflammation and fibrosis is not known. Increased susceptibility to oxidative stress is likely to play a role. Several patient characteristics have been associated with more severe histological findings in patients with NAFLD, including type 2 diabetes, hypertension, age over 40 years, and higher transaminases. Liver biopsy is, however, required to accurately grade and stage NAFLD histologically. Although the natural history of NAFLD is relatively poorly defined, NAFLD is increasingly recognized as an important cause of decompensated liver disease. Weight reduction and improved insulin sensitivity are associated with improved biochemical and histological parameters of NAFLD. There are, however, no proven safe and efficacious pharmacological treatments for NAFLD.