**4. Current therapeutic target**

The information above pointed out the various pathways associated with NAFLD pathogenesis and the role of HDL as a molecular modifier of NAFLD. Finding the most effective therapeutic targets is now much easier, due to our growing understanding of the pathophysiology of NAFLD. Indeed, correction and management of established NAFLD and NASH-associated factors implicated with the pathogenesis and progression, including excessive dietary energy and fructose intake, the extent of obesity, hyperlipidaemia, degree of IR, DM and oxidative stress are the current therapeutic targets of NAFLD and NASH treatment [2]. The current therapies available are projected toward improving the factors that suppress the disease pathogenesis, including exercise, weight loss, modification of lifestyle, decreasing IR and promoting DM control. At end-stage cirrhosis, liver transplant appears to be the only treatment option. Therapies that can cure or prevent fibrosis are essential in this regard because it is known that the existence of fibrosis in NAFLD is linked with other liver-associated complications [4]. Antioxidants, such as vitamins C, E, and betaine, iron depletion, statins, and pentoxifylline are some of the current treatments being evaluated in NAFLD and NASH. Others, including Glucagon-like peptide-1 (GLP-1) based therapy, may be an advanced therapeutic alternative to inhibit the development of NAFLD. Drugs like exenatide, have been demonstrated to boost insulin secretion, inhibit glucagon secretion, suppress gastric emptying, and promote satiety with weight loss, demonstrated in both animal models and DM individuals [2]. Since angiotensin has been demonstrated to encourage myofibroblast survival and liver fibrosis, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are anticipated to have significant effects, such as antifibrotic. The proliferative, contractile, and fibrogenic activities of HSCs are closely regulated by a wide number of cytokines, whose antagonistic effects constitute another possible target for antifibrotic treatments [27]. Platelet-derived growth factor (PDGF), transforming growth factor beta-1 (TGF-β1), connective tissue growth factor (CTGF), endothelin-1 (ET-1), thrombin, vascular endothelial growth factor (VEGF), fibroblast growth factor, and insulin-like growth factor are potential candidates, that exert their effects through tyrosine-kinase receptors [4]. Additionally, inhibiting ER stress

and modifying the gut-liver axis utilizing pre- and probiotics are two other possible targets. A Mediterranean diet has been shown to minimize oxidative stress, and high daily doses of vitamin E have been shown to cause the resolution of NASH in 36% of treated individuals. Silymarin reduced transaminase levels in NAFLD patients, and long-term use of the drug may help lessen fibrosis and halt the progression of liver disease in NAFLD and NASH patients [4].
