Nonalcoholic fatty liver disease and the metabolic syndrome

Abstract Purpose of review Clinical, epidemiological and biochemical data strongly support the concept that nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Insulin resistance is the common soil connecting obesity, diabetes, hypertension and dyslipidemia with fatty liver and the progression of hepatic disease to steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. Recent findings The association of NAFLD with the features of the metabolic syndrome has been confirmed in several epidemiological studies. The diagnostic and clinical significance of raised liver enzymes has been questioned; advanced hepatic disease may also be present in subjects with ultrasonographycally detected steatosis and normal aminotransferase levels. The role of adipokynes (leptin, adiponectin) and cytokines (tumor necrosis factor-a, interleukin-6, transforming growth factor-b) in disease progression is probably pivotal, mediated by oxidative stress. The importance of iron accumulation in this process has not been confirmed. Treatments aimed at weight loss remain a primary option; among pharmacological interventions insulin sensitizers (glitazones and metformin) have confirmed beneficial effects on both biochemical and histological data, but new treatments are on the horizon. Summary NAFLD prevalence in western countries is high, and there is a trend towards a further increase, with millions people at risk of advanced liver disease. The epidemiological evidence, the lifestyle origin of the disease and the cost of pharmacotherapy make prevention a primary goal, and will contribute to make behavior therapy the background treatment. We need specific programs and carefully controlled, randomized studies to tackle simultaneously all the components of the metabolic syndrome.