Almeqdadi Mohammad, Gordon Fredric D
Division of Transplantation and Hepatobiliary Diseases, Lahey Hospital & Medical Center, Burlington, Massachusetts.
Abdominal Transplant Institute, Tufts Medical Center, Boston, Massachusetts.
Gastro Hep Adv. 2023 Oct 6;3(3):344-352. doi: 10.1016/j.gastha.2023.09.013. eCollection 2024.
Farnesoid X receptor (FXR) agonists have emerged as a promising therapeutic strategy for the management of various gastrointestinal (GI) diseases, including primary biliary cholangitis, nonalcoholic fatty liver disease, inflammatory bowel disease, alcohol-related liver disease, and primary sclerosing cholangitis. In this review, we discuss the mechanisms of action of FXR agonists, including their metabolic and immunomodulatory effects, and provide an overview of the clinical evidence supporting their use in the treatment of GI diseases. We also highlight the safety, adverse effects, and potential drug interactions associated with FXR agonists. While these agents have demonstrated efficacy in improving liver function, reducing hepatic steatosis, and improving histological endpoints in primary biliary cholangitis and nonalcoholic fatty liver disease, further research is needed to determine their long-term safety and effectiveness in other GI diseases, such as inflammatory bowel disease, alcohol-related liver disease, and primary sclerosing cholangitis. Additionally, the development of next-generation FXR agonists with improved potency and reduced side effects could further enhance their therapeutic potential.
法尼酯X受体(FXR)激动剂已成为一种有前景的治疗策略,用于管理各种胃肠道(GI)疾病,包括原发性胆汁性胆管炎、非酒精性脂肪性肝病、炎症性肠病、酒精性肝病和原发性硬化性胆管炎。在本综述中,我们讨论了FXR激动剂的作用机制,包括其代谢和免疫调节作用,并概述了支持其用于治疗胃肠道疾病的临床证据。我们还强调了与FXR激动剂相关的安全性、不良反应和潜在药物相互作用。虽然这些药物已在改善肝功能、减少肝脂肪变性以及改善原发性胆汁性胆管炎和非酒精性脂肪性肝病的组织学终点方面显示出疗效,但仍需要进一步研究以确定它们在其他胃肠道疾病(如炎症性肠病、酒精性肝病和原发性硬化性胆管炎)中的长期安全性和有效性。此外,开发具有更高效力和更少副作用的下一代FXR激动剂可能会进一步提高其治疗潜力。