Non-alcoholic fatty liver disease: Mechanisms and treatment

Non-alcoholic fatty liver disease (NAFLD), the excess hepatic accumulation of fat in the form of triglycerides, has become a global epidemic. This chapter reviews the epidemiology of NAFLD, and discusses mechanisms of injury and progression, the natural history of the disease, and management options for patients. In contrast to NAFLD, that can be identified reliably through imaging modalities, the diagnosis of non-alcoholic steatohepatitis (NASH) remains a histological one. NAFLD occurs together with obesity, diabetes, and the metabolic syndrome. The non-synonymous single nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase domain containing-3 gene encoding the adiponutrin protein has consistently shown a strong association with NAFLD. A SNP in the transmembrane 6 superfamily member 2 gene was found to be associated with NAFLD. Oxidative stress has been implicated in the pathogenesis of NASH. The lipotoxic damage to hepatocytes activates regulated death pathways in NASH, predominantly apoptosis, with activation of both intrinsic and extrinsic pathways.