Nonalcoholic fatty liver disease and atherosclerosis

Atherosclerosis is a complex inflammatory disease comprising multiple plaque phenotypes. The development of advanced atheromatous plaques with necrotic core represents the result of the invasion of lipid pools by macrophages. The release of activated proteolytic enzymes degrades the surrounding tissue and contributes to the formation of vulnerable plaque. Thinning of the fibrous cap and necrotic core expansion are considered to be critical for the progression toward plaque rupture and acute thrombosis. The pathogenic mechanisms leading the progression of atherosclerotic lesions are various and involve endothelial cells, inflammatory cells, and platelets. Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases ranging from simple fatty liver to nonalcoholic steatohepatitis (NASH) and may progress to cirrhosis and hepatocellular carcinoma. The prevalence of this pathology is quite high in the general population and is one of the most important causes of liver-related morbidity and mortality in children. NAFLD is considered the hepatic feature of the metabolic syndrome and this has stimulated interest in its possible role in the atherosclerosis development. Clinical observations indicated that NAFLD might be an independent risk factor for coronary artery disease. Moreover, NASH may increase atherosclerotic and cardiovascular risks by local overexpression of inflammatory mediators, endothelial damage, and regulators of blood pressure. NASH development is correlated with hepatic progenitor cell activation and the release of proatherogenic adipokines. These aspects suggest the necessity for an early therapeutic intervention in NASH patients, not only for ameliorating the liver injury, but also for improving the systemic proatherogenic state.