Nonalcoholic fatty liver (NAFL): Overview

Nonalcoholic fatty liver (NAFL) or nonalcoholic fatty liver disease (NAFLD) as it is often called, is increasingly recognized as a common and potentially severe condition often associated with obesity, type 2 diabetes, and hyperlipidemia. The spectrum of disorders which fall under the term 'NAFL' include simple steatosis, steatosis with mild inflammation, and steatosis with inflammation and varying degrees of fibrosis. Most investigators reserve the term 'NASH' (nonalcoholic steatohepatitis) for those patients who have some degree of fibrosis, usually associated with increased numbers of ballooned hepatocytes. The prognosis varies, but it is now evident that a substantial portion of patients, especially those with NASH, will progress to cirrhosis with all of the attendant complications, and some may ultimately develop hepatocellular cancer. Well-developed cirrhosis may lose its fat content and appear as 'cryptogenic cirrhosis'. Lipid peroxidation of the excess oil in the liver appears to be the major pathogenic mechanism. The process appears to alter mitochondrial form and function. Initial treatment usually involves exercise and dietary modifications. Patients who fail this approach or who have more advanced conditions initially may be candidates for more aggressive measures, including drug therapy. Many agents have been reported in small series but all remain investigational.