Dahiya Khushi, Palkar Mahesh, Sharma Sanjay
Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's, NMIMS, Deemed to Be University, Vile Parle West, Mumbai, Maharashtra, 400056, India.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Aug;398(8):9703-9720. doi: 10.1007/s00210-025-03880-y. Epub 2025 Mar 11.
Non-alcoholic steatohepatitis (NASH) is a severe manifestation of non-alcoholic fatty liver disease (NAFLD), which is characterized by hepatic steatosis, inflammation, and hepatocyte destruction. Newly adopted nomenclature, metabolic dysfunction-associated fatty liver disease (MAFLD), allows to signify the importance of metabolic dysfunction. For which the current treatment options are limited and often associated with adverse effects, creating a need for targeted therapies. This manuscript evaluates resmetirom (RMT), a selective thyroid hormone receptor (THR)-β agonist, as a promising treatment for MASH (metabolic associated steatohepatitis). The pharmacokinetic properties, synthesis pathways, and therapeutic effects of RMT were reviewed. Preclinical and clinical trials assessed the efficacy and safety of RMT at doses of 80 mg and 100 mg, with observations that included improvements in liver histology and fibrosis scores. The manuscript also explored the role of RMT in multimodal treatment strategies alongside lifestyle modifications. RMT enhances fatty acid oxidation, modulates mitophagy, and exerts potential anti-fibrotic effects, leading to improved hepatic function and reduced disease progression. Clinical trials demonstrated significant improvements in liver histology and fibrosis scores with a favorable safety profile. RMT offers therapeutic benefits with fewer side effects compared to existing treatments for advanced MASH. RMT represents a promising therapeutic option for patients with advanced MASH, offering improved outcomes and reduced adverse effects. Further studies are needed to evaluate the long-term effectiveness, affordability, and accessibility of RMT.
非酒精性脂肪性肝炎（NASH）是非酒精性脂肪性肝病（NAFLD）的严重表现形式，其特征为肝脂肪变性、炎症和肝细胞破坏。新采用的命名法，即代谢功能障碍相关脂肪性肝病（MAFLD），能够表明代谢功能障碍的重要性。目前针对MAFLD的治疗选择有限，且常常伴有不良反应，因此需要有针对性的治疗方法。本手稿评估了瑞美替隆（RMT），一种选择性甲状腺激素受体（THR）-β激动剂，作为治疗代谢相关脂肪性肝炎（MASH）的一种有前景的疗法。对RMT的药代动力学特性、合成途径及治疗效果进行了综述。临床前和临床试验评估了80毫克和100毫克剂量的RMT的疗效和安全性，观察结果包括肝脏组织学和纤维化评分的改善。该手稿还探讨了RMT在与生活方式改变相结合的多模式治疗策略中的作用。RMT可增强脂肪酸氧化、调节线粒体自噬，并发挥潜在的抗纤维化作用，从而改善肝功能并减缓疾病进展。临床试验表明，RMT在肝脏组织学和纤维化评分方面有显著改善，且安全性良好。与晚期MASH的现有治疗方法相比，RMT的副作用更少，具有治疗益处。对于晚期MASH患者，RMT是一种有前景的治疗选择，可带来更好的治疗效果并减少不良反应。需要进一步研究来评估RMT的长期有效性、可承受性和可及性。
