Non-alcoholic steatohepatitis (NASH) is a spectrum of histological liver pathologies ranging from hepatocyte fat accumulation, hepatocellular ballooning, lobular inflammation, and pericellular fibrosis. Based on early investigations, it was discovered that visceral fat accumulation, hepatic insulin resistance, and atherogenic dyslipidemia are pathological triggers for NASH progression. As these pathogenic features are common with obesity, type 2 diabetes (T2D), and atherosclerosis, therapies that target dysregulated core metabolic pathways may hold promise for treating NASH, particularly as first-line treatments. In this review, the latest clinical data of nuclear hormone-based and peptide hormone-based drug candidates for NASH will be reviewed and contextualized, culminating with a discovery research perspective on emerging combinatorial therapeutic approaches that merge nuclear hormone and peptide hormone strategies.

非酒精性脂肪性肝炎 (NASH) 是一系列肝脏组织病理学，包括肝细胞脂肪堆积、肝细胞气球样变、小叶炎症和细胞周围纤维化。根据早期研究，发现内脏脂肪堆积、肝脏胰岛素抵抗和致动脉粥样硬化性血脂异常是 NASH 进展的病理触发因素。由于这些致病特征在肥胖、2 型糖尿病 (T2D) 和动脉粥样硬化中很常见，针对失调的核心代谢途径的疗法可能有望治疗 NASH，尤其是作为一线治疗。在本次审查中，将审查并结合基于核激素和肽激素的 NASH 候选药物的最新临床数据，