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Resmetirom and Thyroid Hormone Receptor-Targeted Treatment for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Resmetirom and Thyroid Hormone Receptor-Targeted Treatment for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

摘要Metabolic dysfunction-associated steatotic liver disease (MASLD) is a rapidly increasing chronic disease worldwide, particularly among patients with type 2 diabetes. Its severe form, metabolic dysfunction-associated steatohepatitis (MASH), is also on the rise. The treatment of MASLD and MASH poses significant challenges. Thyroid hormones and their receptors thyroid hormone receptor (TR) agonists, especially resmetirom, have shown potential in improving metabolism and reducing liver inflammation. Thyroid hormones play a crucial role in regulating metabolism and maintaining physiological balance. However, in patients with MASLD, there is a reduced conversion of 3,3′,5,5′-tetraiodo- L-thyronine (T 4) to biologically active 3,5,3′-triiodo- L-thyronine (T 3), resulting in decreased T 3 levels and impaired hepatic TR signaling. This hormonal imbalance is associated with disrupted hepatic lipid metabolism. Resmetirom, an oral selective TR agonist that specifically targets hepatocytes, was approved by the Food and Drug Administration (FDA) in March 2024 for the treatment of moderate to severe liver fibrosis in non-cirrhotic adults with MASH. This approval was based on the results of the MAESTRO clinical program, which includes multiple-stage research designs such as the MAESTRO-NASH, MAESTRO-NAFLD-1, MAESTRO-NAFLD-OLE, and MAESTRO-NASH-OUTCOMES, aims to evaluate the efficacy and safety of resmetirom in different populations of MASH patient. Although the approval of resmetirom represents a significant milestone in the treatment of MAFLD and MASH, many questions remain regarding its long-term effectiveness and impact on clinical outcomes. Ongoing research, particularly through the MAESTRO program, holds promise for providing additional insights into the long-term management of MASLD using resmetirom and other similar medications.

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作者 Liu Chang-Hai [1] Zeng Qing-Min [2] Hu Teng-Yue [3] Huang Yu [4] Song Yongfeng [5] Guan Haixia [6] Rockey Don C. [7] Tang Hong [1] Li Sheyu [4] 学术成果认领
作者单位 Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China [1] West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China [2] Laboratory of Infectious and Liver Diseases, Institute of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China [3] Department of Endocrinology and Metabolism, Department of Guideline and Rapid Recommendation, Cochrane China Center, MAGIC China Center, Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China [4] Department of Endocrinology, Central Hospital affiliated to Shandong First Medical University, Jinan, Shandong, China [5] Department of Endocrinology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China [6] Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina, USA [7]
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DOI 10.1002/poh2.100
发布时间 2025-04-15
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