与代谢功能障碍相关的脂肪肝炎 (MASH) 的治疗景观
Albert Do1,2, Frhaan Zahrawi1, Wajahat Z Mehal3,4
1Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Nature reviews. Drug discovery
|November 28, 2024
概括
与代谢功能障碍相关的脂肪性肝病 (MASLD) 和其严重形式MASH是全球流行病. 包括resmetirom在内的新疗法提供了希望,但需要进一步研究最佳治疗策略和患者的治疗结果.
科学领域:
- 肝病学和代谢疾病研究.
背景情况:
- 与代谢功能障碍相关的脂肪性肝病 (MASLD) 和其严重形式,代谢功能障碍相关的脂肪性肝炎 (MASH),代表着日益严重的全球健康危机.
- 这些疾病是由慢性营养过度和遗传因素造成的,导致肝损伤,炎症和肝硬化.
研究的目的:
- 审查与药物开发相关的MASLD/MASH的病变发生.
- 讨论MASH目前和新兴的治疗策略.
- 探索用于治疗MASH的组合疗法的潜力.
主要方法:
- 对MASLD/MASH病原和治疗方法的当前文献的综述.
- 讨论药物开发方面的考虑,包括安慰剂反应,试验终点和副作用概况.
- 对两种主要治疗途径的分析:甲状腺激素受体β激动剂和隐类同类药物.
主要成果:
- 甲状腺激素受体βagonist的resmetirom是MASLD/MASH的第一个批准治疗方法,刺激了临床兴趣.
- 甲状腺激素受体β激动剂和脂肪酸合成酶抑制剂直接向肝脏.
- 胰岛素类似物,如西马格卢提德,改善全身新陈代谢,使肝脏自我调节和MASH逆转.
结论:
- 虽然resmetirom提供了一个新的治疗选择,但进一步的临床研究对于优化MASH治疗至关重要.
- 治疗策略包括直接针对肝脏或改善全身新陈代谢.
- 组合疗法可能提供一种更全面的方法来管理MASH.
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