胆汁淤积性肝病的治疗靶点及药物应用前景

New therapeutic targets and drugs for cholestatic liver disease

胆汁淤积性肝病是由胆管的破坏、胆汁酸的积聚和炎症过程的持续导致胆管细胞及肝细胞的损伤而引起。若不及时治疗,胆汁淤积会导致肝纤维化、肝硬化甚至出现终末期肝病。原发性胆汁性胆管炎(PBC)和原发性硬化性胆管炎(PSC)是成人中最常见的2种胆汁淤积性肝病,其病因目前尚不明确。虽然熊去氧胆酸(UDCA)可以较好地改善PBC患者的预后,延长患者肝移植的存活率,但存在部分患者对UDCA治疗无应答的现象。此外,目前尚无有效药物治疗PSC。随着近年来胆汁酸调节分子机制的研究进展及免疫途径的理解加深,涌现了越来越多新的药物。介绍了近年来PBC及PSC新兴治疗靶点及相关药物方面的研究进展。

Cholestatic liver disease is caused by the damage of bile duct cells and hepatocytes due to bile duct injury,accumulation of bile acids,and persistent inflammation.If it is not treated in time,cholestasis can lead to liver fibrosis,liver cirrhosis,and even end-stage liver disease.Primary biliary cholangitis(PBC)and primary sclerosing cholangitis(PSC)are the two most common cholestatic liver diseases in adults,with unknown causes.Although ursodeoxycholic acid(UDCA)can improve the prognosis of PBC patients and prolong survival time after liver transplantation,some patients have no response to UDCA.In addition,there are still no effective pharmacotherapies for PSC.With the research advances in molecular mechanism of bile acid regulation and a deeper understanding of immune pathways in recent years,several new drugs have emerged.This article introduces the new therapeutic targets and drugs for PBC and PSC.