**1. Introduction**

Non-alcoholic fatty liver disease is defined as a broad spectrum of hepatic histopathological changes, from a non-inflammatory intracellular accumulation of lipid to NASH, which can develop into hepatic fibrosis, cirrhosis, or HCC [1]. NAFLD is the excessive hepatic deposition of neutral lipids, initiated by an imbalance between lipid availability and clearance. Hepatic lipid accumulation in NAFLD is caused by changes in intracellular cholesterol transport and imbalanced cellular cholesterol homeostasis, characterized by the activations of cholesterol biosynthetic pathways. Enhanced cholesterol de-esterification, modulations of bile acid synthetic pathways and cholesterol export [2]. Through the activation of intracellular signaling pathways in Kupffer cells (KCs), hepatic Stellate cells (HSCs), and hepatocytes, the hepatic lipids accumulation causes liver damage, inflammation and fibrogenesis. Additionally, the mitochondrial dysfunction in the liver may cause an increase in the formation of reactive oxygen species (ROS), which could in turn causes endoplasmic reticulum (ER) stress and death by triggering the unfolded protein response [2]. These actions result in a vicious cycle that supports the progress of steatosis, liver damage and hepatocyte death, which may eventually result in disease progression. Triglycerides (TG) and HDL-C frequently undergo distinctive alterations in atherogenic dyslipidaemia, which is intimately associated with NAFLD. Indeed, atherogenic dyslipidaemia is closely linked to NAFLD, attributed to modifications in TG and HDL-C, hence, constant monitoring of atherosclerotic lipids is essential to evaluate the risk of NAFLD [1, 3, 4].

The incidence of NAFLD is currently around 25% worldwide, with a significant regional variation in the Middle East (32%), South America (31%) as well as the United States (24.1%) and Africa (14%). The prevalence also varies with metabolic disorders, which indicated that approximately 90% of obese individuals, 65% of overweight people, and up to 70% of diabetes mellitus (DM) patients have NAFLD. NAFLD has also been investigated in most ethnic groups but with a lower prevalence in African Americans compared with European-Americans and Hispanics [2, 5]. HDL-C has been considered to modulate NAFLD through several pathways that promote cholesterol efflux in the system, including the reverse cholesterol transport pathway [2, 5], however, essential information to fully understand the impact of HDL-C in NAFLD are limited. In this review, progress on the existing knowledge of the dysregulated cholesterol homeostasis in NAFLD and the cellular mechanisms underlying hepatic lipids toxicity and its role in liver injury were elaborated. The contribution of HDL-C as a molecular modulator and the therapeutic implications of this knowledge were also discussed.
