DOI: 10.1515/mr-2024-0007
Hormone-based pharmacotherapy for metabolic dysfunction-associated fatty liver disease
Zara Siu Wa Chui1
Yaqian Xue2
Aimin Xu3
1.State Key Laboratory of Pharmaceutical Biotechnology,The University of Hong Kong,Hong Kong SAR,China;Department of Medicine,The University of Hong Kong,Hong Kong SAR,China;School of Biomedical Sciences,The University of Hong Kong,Hong Kong SAR,China2.State Key Laboratory of Pharmaceutical Biotechnology,The University of Hong Kong,Hong Kong SAR,China;Department of Medicine,The University of Hong Kong,Hong Kong SAR,China3.State Key Laboratory of Pharmaceutical Biotechnology,The University of Hong Kong,999077,Hong Kong SAR,China;Department of Medicine,The University of Hong Kong,999077,Hong Kong SAR,China;Department of Pharmacology and Pharmacy,The University of Hong Kong,999077,Hong Kong SAR,China
摘要：Metabolic dysfunction-associated fatty liver dis-ease(MAFLD)has reached epidemic proportions globally in parallel to the rising prevalence of obesity.Despite its signif-icant burden,there is no approved pharmacotherapy specif-ically 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 receptor β(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 thera-peutic efficacy in mitigating hepatic steatosis,inflammation and fibrosis,but also improve metabolic profiles.Further-more,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.
机标关键词：metabolicassociateddiseasedysfunctionfattyhormone-basedliverpharmacotherapy
论文发表日期：2024-04-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：11( 158-168 )
英文信息