Pathophysiology and clinical management of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver dysfunction in the Western world. It defines the spectrum from steatosis to cirrhosis and hepatocellular carcinoma. The predominant cause of NAFLD is obesity. Its pathogenesis involves insulin resistance, hepatic fat deposition, consequent increased oxidant stress, activation of matrix producing cells and propagation of fibrogenesis with increasing indication for liver transplantation. NAFLD rates are rising in tandem with the population prevalence of obesity. Mechanistically, there is emerging evidence that maternal obesity may program offspring obesity with ensuing increased susceptibility to NAFLD in adulthood, via permanent changes to structure and/or physiology in utero and lactation. Presently, NAFLD cannot be diagnosed with a single test and is largely one of exclusion. Given its association with obesity, the initial treatment is diet and increased physical activity. Subsequent interventions target facets of the dysmetabolic syndrome with the aim of benefiting liver function. Emerging therapies include glitazones, vitamin E, angiotensin receptor blockers and α-adrenoceptor antagonists.