Fatty liver and global cardiometabolic risk

Abstract

Non-alcoholic fatty liver disease (NAFLD) can be found in approximately 30% of adults in industrialized societies. Non-alcoholic steatohepatitis (NASH) is its most severe histological form and progresses to cirrhosis in 20% of these patients. Once developed, 30% to 40% of patients with cirrhosis will suffer liver-related death. NAFLD is considered the hepatic manifestation of the metabolic syndrome. Recent findings linking the components of metabolic syndrome with NAFLD and the progression to nonalcoholic steatohepatitis will be reviewed; in particular, the role of visceral adipose tissue, insulin resistance, adipocytokines, oxidative stress and diminished antioxidants within the liver in the exacerbation of these conditions. It is now widely accepted that non-hepatic mechanisms are largely responsible for the development of insulin resistance, which causes hepatic steatosis. Insulin resistance, a key feature of metabolic syndrome, is crucial for NASH development. We have a classical chicken-egg problem: insulin resistance causes hepatic steatosis or vice-versa? A possible sequence of the pathogenetic events is the following: increased free fatty acid supply - increased de novo lipogenesis - triglyceride and VLDL overproduction - atherogenic dyslipidemia- oxidative stress (lipid oxidation and peroxidation) - exhaustion of antioxidant defense system- "Tsunami" of inflammatory cytokines- fibrosis- carcinogenesis. Given the strong association of NAFLD with metabolic syndrome, early recognition, assessment and management are essential. The management emphasizes weight reduction and attention to global cardiometabolic risk factors, similar to recommendations for management of the elements of metabolic syndrome.