Hormone-based pharmacotherapy for metabolic dysfunction-associated fatty liver disease

作     者：Zara Siu Wa Chui Yaqian Xue Aimin Xu 

作者机构：State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong KongHong Kong SARChina Department of MedicineThe University of Hong KongHong Kong SARChina School of Biomedical SciencesThe University of Hong KongHong Kong SARChina State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong Kong999077Hong Kong SARChina Department of MedicineThe University of Hong Kong999077Hong Kong SARChina Department of Pharmacology and PharmacyThe University of Hong Kong999077Hong Kong SARChina 

出 版 物：《Medical Review》 (医学评论（英文）)

年 卷 期：2024年第4卷第2期

页      面：158-168页

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by National Key R&D Program of China(2022YFA0806102) the Hong Kong Research Grants Council/Area of Excellence(AoE/M-707/18) Health and Medical Research Fund(06172446) General Research Fund(17127518) as well as the National Natural Science Foundation of China(82070860,82161138026) 

主　　题：metabolic hormones metabolic dysfunctionassociated steatohepatitis(MASH) liver fibrosis biopharmaceutical development clinical trials 

摘      要：Metabolic dysfunction-associated fatty liver disease(MAFLD)has reached epidemic proportions globally in parallel to the rising prevalence of *** its significant burden,there is no approved pharmacotherapy specifically tailored for this *** potential drug candidates for MAFLD have encountered setbacks in clinical trials,due to safety concerns or/and insufficient therapeutic ***,several investigational drugs that mimic the actions of endogenous metabolic hormones,including thyroid hormone receptorβ(THRβ)agonists,fibroblast growth factor 21(FGF21)analogues,and glucagon-like peptide-1 receptor agonists(GLP-1RAs),showed promising therapeutic efficacy and excellent safety *** them,resmetirom,a liver-targeted THRβ-selective agonist,has met the primary outcomes in alleviation of metabolic dysfunction-associated steatohepatitis(MASH),the advanced form of MAFLD,and liver fibrosis in phase-3 clinical *** hormone-based pharmacotherapies not only exhibit varied degrees of therapeutic efficacy in mitigating hepatic steatosis,inflammation and fibrosis,but also improve metabolic ***,these three hormonal agonists/analogues act in a complementary manner to exert their pharmacological effects,suggesting their combined therapies may yield synergistic therapeutic *** in-depth studies on the intricate interplay among these metabolic hormones are imperative for the development of more efficacious combination therapies,enabling precision management of MAFLD and its associated comorbidities.