Non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) refers to the accumulation of hepatic steatosis not due to excess alcohol consumption. The prevalence of NAFLD is up to 30% in developed countries and nearly 10% in developing nations, making NAFLD the most common liver condition in the world. The pathogenesis of NAFLD is related to insulin resistance and, thus, it is frequently found in individuals who have central obesity or diabetes. Insulin resistance and excess adiposity are associated with increased lipid influx into the liver and increased de novo hepatic lipogenesis, promoting hepatic triglyceride accumulation. Defects in lipid utilization via mitochondrial oxidation and lipid export may also contribute to hepatic lipid build-up. Adipocytokine alterations, lipotoxicity from saturated fatty acids and fructose have been all been implicated in causing hepatocyte injury in NAFLD through pathways involving oxidative and endoplasmic reticulum stress. Clinically, NAFLD is commonly asymptomatic and frequently detected incidentally by blood liver function tests or imaging performed for other reasons. Subjects with NAFLD have a higher mortality rate than the general population and are at increased risk of developing cardiovascular disease and diabetes in the future. Histologically, NAFLD occurs as a spectrum from mild hepatic steatosis only, to non-alcoholic steatohepatitis (NASH) characterized by hepatocellular injury and inflammation, to cirrhosis. A diagnosis of NASH with associated fibrosis heralds a more significant prognosis as it is more likely to progressive to cirrhosis with complications of hepatic failure and hepatocellular carcinoma. Currently, the diagnosis of NASH requires a liver biopsy, however, serum based markers of hepatocyte apoptosis such as cytokeratin-18 fragments offer promise as accurate non-invasive diagnostic tests. Treatment of NAFLD revolves around addressing concomitant metabolic risk factors and improving insulin resistance through weight loss measures and exercise. Insulin sensitizing agents such as pioglitazone and anti-oxidant agents such as vitamin E show some promise in improving liver histology in patients with NASH, however, the long-term benefit of these medications has not been demonstrated.