ABSTRACT
Mechanisms ...................................................................................... 105 7.3.4 Practical Applications: Theoretical Aspects..................................... 106
7.4 Summary Points ........................................................................................... 108 References .............................................................................................................. 108
Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver condition in developed countries, and its prevalence is increasing worldwide. NAFLD, which affects 20-30% of the adult population in Western countries, is strongly associated with the metabolic syndrome. The spectrum of NAFLD includes simple steatosis (fatty liver), nonalcoholic steatohepatitis (NASH), and cirrhosis. Most people with NAFLD have simple steatosis, a generally benign condition. NASH, the more
severe form of NAFLD, is less common, affecting 2-3% of the population. It is characterized by hepatocyte injury, inammation, and brosis, and progresses to cirrhosis in 15-25% of patients (de Alwis and Day, 2008; Younossi, 2008). The pathogenesis of NASH is thought to involve “multiple” hits. Insulin resistance (IR) is usually the rst hit leading to steatosis, which can, in turn, worsen hepatic IR. Further hits include oxidative stress, endotoxins, cytokines, and environmental toxins. Potential sources of oxidative stress in NAFLD include products of mitochondrial and peroxisomal fatty acid oxidations, cytochrome P450 activity, cytokine-mediated inammation, apoptosis, and iron. Oxidative stress promotes lipid peroxidation of hepatocyte membranes, resulting in hepatocyte injury, secretion of proinammatory cytokines, and stellate cell activation leading to brosis (Edmison and McCullough, 2007; London and George, 2007).
