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

作　　者：Zara Siu Wa Chui Yaqian Xue Aimin Xu 

机构地区：[1]State Key Laboratory of Pharmaceutical Biotechnology,The University of Hong Kong,Hong Kong SAR,China [2]Department of Medicine,The University of Hong Kong,Hong Kong SAR,China [3]School of Biomedical Sciences,The University of Hong Kong,Hong Kong SAR,China [4]State Key Laboratory of Pharmaceutical Biotechnology,The University of Hong Kong,999077,Hong Kong SAR,China [5]Department of Medicine,The University of Hong Kong,999077,Hong Kong SAR,China [6]Department of Pharmacology and Pharmacy,The University of Hong Kong,999077,Hong Kong SAR,China

出　　处：《Medical Review》2024年第2期158-168,共11页医学评论（英文）

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).

摘　　要：Metabolic dysfunction-associated fatty liver disease(MAFLD)has reached epidemic proportions globally in parallel to the rising prevalence of obesity.Despite its significant burden,there is no approved pharmacotherapy specifically tailored for this disease.Many potential drug candidates for MAFLD have encountered setbacks in clinical trials,due to safety concerns or/and insufficient therapeutic efficacy.Nonetheless,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 profiles.Among 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 trials.These hormone-based pharmacotherapies not only exhibit varied degrees of therapeutic efficacy in mitigating hepatic steatosis,inflammation and fibrosis,but also improve metabolic profiles.Furthermore,these three hormonal agonists/analogues act in a complementary manner to exert their pharmacological effects,suggesting their combined therapies may yield synergistic therapeutic benefits.Further 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.

关 键 词：metabolic hormones metabolic dysfunctionassociated steatohepatitis(MASH) liver fibrosis biopharmaceutical development clinical trials 

分 类 号：R575.5[医药卫生—消化系统]