Nonalcoholic Fatty Liver Disease (NAFLD) - A Disease of New Era

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the term used to describe the alcohol-like liver injury that occurs in the absence of alcohol abuse (alcohol consumption of over 20 g/day excludes the condition). It includes a range of histological abnormalities including simple steatosis or fatty liver, non-alcoholic steatohepatitis (NASH) and NAFLD induced cirrhosis. Its increasing prevalence in western countries, the diagnostic difficulties by noninvasive tests, and the possibility of progression to advanced fibrosis and even cirrhosis make NASH a challenge for physicians. NASH is frequently associated with type 2 diabetes and the metabolic syndrome, and several genetic and acquired factors are involved in its pathogenesis. Insulin resistance plays a central role in the development of a steatotic liver, which becomes vulnerable to additional injuries. Several cyclic mechanisms leading to self-enhancement of insulin resistance and hepatic accumulation of fat have been recently identified. Excess intracellular fatty acids, oxidant stress, tumor necrosis factor, and mitochondrial dysfunction are causes of hepatocellular injury, thereby leading to disease progression and to the establishment of NASH. Intestinal bacterial overgrowth also plays a role, by increasing production of endogenous ethanol and proinflammatory cytokines. Therapeutic strategies aimed at modulating insulin resistance, managing risk factors, including reduction of weight normalizing lipoprotein metabolism, and down regulating inflammatory mediators with probiotics have promising potential.  

DOI = 10.3329/jom.v8i1.1375

J MEDICINE 2007; 8 : 17-27