原发性胆汁性胆管炎的药物治疗新靶点

Novel therapeutic targets for primary biliary cholangitis

原发性胆汁性胆管炎以进展性胆汁淤积,肝内中小胆管非化脓性炎症为表现,最终发展成肝硬化、肝癌,严重威胁患者生命。研究发现熊去氧胆酸可有效治疗原发性胆汁性胆管炎。对熊去氧胆酸反应较差的患者接受移植或死亡的比例逐年增加,亟需新治疗方案。新药物作用于疾病进展的关键进程,如"上游"免疫反应,"中游"胆道损伤和"下游"纤维化进程。针对不同通路的多药物联合治疗是未来的发展趋势。总结了目前原发性胆汁性胆管炎的潜在治疗方案,评估了治疗实施所面临的挑战。

Primary biliary cholangitis （ PBC ） is a chronic autoimmune - mediated liver disease manifesting as progressive cholestasis and non - purulent inflammation in small - and medium - sized intrahepatic bile ducts. It finally progresses to liver cirrhosis and liver cancer and greatly threatens patient＇s life. Studies have found that ursodeoxyeholie acid （UDCA） can treat PBC effectively. There is a constant increase in the proportion of patients with poor response to UDCA who have undergone transplantation or died, and theretore, new therapeutic regi- mens should be developed as soon as possible. It is necessary to develop new drugs which act on the key processes of disease progression, such as the ＂upstream＂ immune response, the ＂midstream＂ bile duct injury, and the ＂downstream＂ fibrotic process. Combination treatment with drugs targeting different pathways is a trend for future development. This article summarizes current potential therapeutic regimens for PBC and assesses the challenges in the treatment of PBC.