**Abstract**

The pathophysiology of non-alcoholic fatty liver disease (NAFLD) can be identified by modifications in lifestyle, diet and inflammation, all of which have significant implications for the severity of the clinicopathologic outcome of the disease. Prolonged accumulation of hepatic lipid may result in hepatic dysfunction, inflammation and advanced forms of NAFLD. NAFLD describes the presence of hepatic steatosis in the absence of alcohol use and other causes of liver disease. It covers a broad spectrum of hepatic histopathological alterations, from a non-inflammatory intracellular accumulation of fat to non-alcoholic steatohepatitis (NASH), which may progress to hepatic fibrosis, cirrhosis, or hepatocellular carcinoma (HCC). Previous evidence has shown that NAFLD is associated with a range of metabolic syndromes, including obesity, hyperlipidaemia, insulin resistance and diabetes. Hepatic fibrosis and cirrhosis are more common in people with NAFLD, which is partly associated with hyperlipidaemia and low high-density lipoprotein-cholesterol (HDL-C) levels. The ability of HDL to facilitate cholesterol efflux, as determined by cholesterol efflux capacity (CEC), has been linked to its hepatoprotective functions in the body. Findings have demonstrated that NAFLD patients have suppressed HDL CEC. This chapter summarizes the molecular mechanisms and pathogenesis involved in NAFLD. The role of HDL as a molecular modulator of NAFLD, clinical implications and the therapeutic targets to prevent NAFLD have also been discussed.

**Keywords:** high-density lipoprotein, non-alcoholic fatty liver disease, pathogenesis and therapeutic targets
