Thyroid hormones (triiodothyronine and thyroxine) are pivotal for metabolic balance in the liver and entire body. Dysregulation of the hypothalamus–pituitary–thyroid axis can contribute to hepatic metabolic disturbances, affecting lipid metabolism, glucose regulation and protein synthesis. In addition, reductions in circulating and intrahepatic thyroid hormone concentrations increase the risk of metabolic dysfunction-associated steatotic liver disease by inducing lipotoxicity, inflammation and fibrosis. Amelioration of hepatic metabolic disease by thyroid hormones in preclinical and clinical studies has spurred the development of thyromimetics that target THRB (the predominant thyroid hormone receptor isoform in the liver) and/or the liver itself to provide more selective activation of hepatic thyroid hormone-regulated metabolic pathways while reducing thyrotoxic side effects in tissues that predominantly express THRA such as the heart and bone. Resmetirom, a liver and THRB-selective thyromimetic, recently became the first FDA-approved drug for metabolic dysfunction-associated steatohepatitis (MASH). Thus, a better understanding of the metabolic actions of thyroid hormones and thyromimetics in the liver is timely and clinically relevant. Here, we describe the roles of thyroid hormones in normal liver function and pathogenesis of MASH, as well as some potential clinical issues that might arise when treating patients with MASH with thyroid hormone supplementation or thyromimetics.

甲状腺激素（三碘甲状腺原氨酸和甲状腺素）对肝脏和全身的代谢平衡至关重要。下丘脑-垂体-甲状腺轴失调会导致肝脏代谢紊乱，影响脂质代谢、葡萄糖调节和蛋白质合成。此外，循环和肝内甲状腺激素浓度的降低通过诱导脂毒性、炎症和纤维化来增加代谢功能障碍相关脂肪性肝病的风险。在临床前和临床研究中，甲状腺激素对肝脏代谢疾病的改善刺激了针对 THRB（肝脏中主要的甲状腺激素受体亚型）和/或肝脏本身的甲状腺激素的发展，以提供对肝脏甲状腺激素调节的代谢途径的更多选择性激活，同时减少主要表达 THRA 的组织（如心脏和骨骼）的甲状腺毒性副作用。Resmetirom 是一种肝脏和 THRB 选择性甲状腺癌，最近成为 FDA 批准的第一个用于治疗代谢功能障碍相关脂肪性肝炎 （MASH） 的药物。因此，更好地了解甲状腺激素和甲状腺激素在肝脏中的代谢作用是及时的和具有临床意义的。在这里，我们描述了甲状腺激素在正常肝功能和 MASH 发病机制中的作用，以及使用甲状腺激素补充剂或甲状腺激素治疗 MASH 患者时可能出现的一些潜在临床问题。