In particular, a decrease in causes a thinner intestinal mucus layer and promotes gut permeability, which allows the leakage of bacterial components. currently in phase II trials, and it is anticipated that this acquisition of more clinical data in the next few years will enable the use of this new class of drugs for the treatment of NASH. Conclusion Oral immunotherapy may provide a novel platform for the treatment of NASH. Introduction: the difficulty associated with developing treatments for non\alcoholic steatohepatitis Globally, non\alcoholic fatty liver disease (NAFLD) is currently the most common liver disease, affecting approximately one\third of the Western world. 1 The incidence and prevalence of this disease are rapidly rising to epidemic proportions around the globe. NAFLD comprises a spectrum of progressive liver diseases that include simple Diosmetin steatosis, non\alcoholic steatohepatitis (NASH), fibrosis, and ultimately cirrhosis, end\stage liver disease and primary liver cancer.2 NASH has been predicted to become the leading cause of liver transplantation in the USA by the year 2020.3 The incidence of hepatocellular carcinoma (HCC) is also rising; hence, HCC has become the primary cause of obesity\related cancer death in middle\aged men in the USA.1 During the Diosmetin process of drug development for NASH, numerous obstacles have been identified in recent years.4 While progress has been achieved in our understanding of the pathophysiology, diagnosis and natural history of NAFLD, no drugs have yet been approved for the treatment of NASH.4 Studies investigating the optimal therapy for NAFLD and NASH have not yet been able to develop a universal treatment protocol.5 Lack of a clear mechanism remains a major difficulty in drug development for NASH, which is caused by a complex interplay between host and environmental factors.3 Thus, the use of pharmacological brokers as an adjunctive therapy to lifestyle modification is crucial, as weight loss is a difficult task to achieve and maintain.6 NAFLD is recognised as the hepatic component of the metabolic syndrome and is associated with liver\related morbidity and mortality as well as an increased risk of cardiovascular disease, type 2 diabetes mellitus, hyperlipidaemia and abdominal obesity.7 Several pharmacological agents have been studied in an effort to improve insulin resistance and to improve the pro\inflammatory mediators responsible for NASH progression.4 Examples of drugs that are effective only in the animal models of NASH but have failed in human trials are as follows: PDE4 inhibitors,8 caspase inhibitors,9 resveratrol,10 omega\3 fatty acid preparations,11 anti\tumour necrosis factor\alpha (TNF\) and probiotics. In addition, most NASH patients use drugs to control type 2 diabetes, such as metformin, sulfonamides and insulin, although these drugs are ineffective for NASH.4, 12 The side effects of several compounds that have demonstrated efficacy in NASH trials are of major concern. Examples are pioglitazones, which were shown in the PIVENS trial to improve some histological features of NASH, and to achieve resolution of steatohepatitis.13 However, glitazones contribute to weight gain and to adipose tissue insulin resistance.14 Their long\term use is associated with bone fractures in women, congestive heart failure and increased risk of bladder cancer.4, 15 Obeticholic acid (OCA) is a synthetic bile acid with picomolar agonistic activity towards the farnesoid X receptor (FXR), as shown in the FLINT trial to improve steatohepatitis and fibrosis.16 Side Diosmetin effects of pruritus and an increase in low\density lipoprotein (LDL) cholesterol are of relevance for their chronic use.17 DNMT3A In the PIVENS trial, vitamin E was shown to improve steatosis, inflammation and ballooning,.