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The Race to Bash NASH: Emerging Targets and Drug Development in a Complex Liver Disease.
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2020-01-13 , DOI: 10.1021/acs.jmedchem.9b01701
F Anthony Romero 1 , Christopher T Jones 1 , Yingzi Xu 1 , Martijn Fenaux 1 , Randall L Halcomb 1
Affiliation  

Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD) characterized by liver steatosis, inflammation, and hepatocellular damage. NASH is a serious condition that can progress to cirrhosis, liver failure, and hepatocellular carcinoma. The association of NASH with obesity, type 2 diabetes mellitus, and dyslipidemia has led to an emerging picture of NASH as the liver manifestation of metabolic syndrome. Although diet and exercise can dramatically improve NASH outcomes, significant lifestyle changes can be challenging to sustain. Pharmaceutical therapies could be an important addition to care, but currently none are approved for NASH. Here, we review the most promising targets for NASH treatment, along with the most advanced therapeutics in development. These include targets involved in metabolism (e.g., sugar, lipid, and cholesterol metabolism), inflammation, and fibrosis. Ultimately, combination therapies addressing multiple aspects of NASH pathogenesis are expected to provide benefit for patients.

中文翻译:

扑灭NASH的竞赛:复杂肝病中的新兴目标和药物开发。

非酒精性脂肪性肝炎(NASH)是非酒精性脂肪肝疾病(NAFLD)的一种严重形式,其特征是肝脏脂肪变性,炎症和肝细胞损伤。NASH是一种严重的疾病,可能会发展为肝硬化,肝衰竭和肝细胞癌。NASH与肥胖症,2型糖尿病和血脂异常的相关性已导致NASH成为代谢综合征的肝脏表现的新图像。尽管饮食和运动可以显着改善NASH的结局,但要想维持这种生活方式,要想显着改变生活方式,可能会充满挑战。药物疗法可能是护理的重要补充,但目前尚无任何药物可用于NASH。在这里,我们回顾了NASH治疗的最有希望的目标以及发展中的最先进的治疗方法。这些包括与代谢有关的目标(例如,糖,脂质和胆固醇代谢),炎症和纤维化。最终,解决NASH发病机制多个方面的联合疗法有望为患者带来益处。
更新日期:2020-01-13
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