Liver Care Network, Swedish Medical Center, Seattle, Washington, USA.
Curr Opin Gastroenterol. 2019 May;35(3):191-196. doi: 10.1097/MOG.0000000000000525.
This review will summarize the use of obeticholic acid (OCA) in treatment of primary biliary cholangitis (PBC). It seeks to discuss the mechanism of action, evidence for use, appropriate clinical use, and common adverse effects of OCA.
PBC is a chronic, progressive cholestatic liver disease that is a chronic progressive that may lead to end-stage liver disease and need for liver transplantation. Ursodeoxycholic acid (UDCA) has been the mainstay of therapy for PBC for decades. Recent research has led to the discovery that bile acids act as hormones and have many effects, one of which is activating the farnesoid X receptor (FXR). Activation of FXR leads to decreased bile acid synthesis, inflammation, and fibrosis of the liver. OCA is a highly potent FXR agonist.
Several clinical trials demonstrated that OCA treatment in PBC led to a significant decrease in serum alkaline phosphatase, a marker for long-term survival. The US FDA-approved OCA in 2016, which led to incorporation of OCA into current guidelines as a second-line treatment for PBC. The most clinically relevant adverse effect of OCA is dose-related pruritus. We review the role of OCA and current guidelines in treatment of PBC.
本文将总结奥贝胆酸(OCA)在原发性胆汁性胆管炎(PBC)治疗中的应用。讨论其作用机制、使用证据、临床应用及常见不良反应。
PBC 是一种慢性进行性胆汁淤积性肝病,可能进展至终末期肝病并需要肝移植。熊去氧胆酸(UDCA)是 PBC 数十年的主要治疗药物。最近的研究发现胆汁酸作为激素发挥作用,具有许多功能,其中之一是激活法尼醇 X 受体(FXR)。FXR 的激活可减少胆汁酸合成、炎症和肝脏纤维化。OCA 是一种强效 FXR 激动剂。
几项临床试验表明,OCA 治疗 PBC 可显著降低血清碱性磷酸酶,这是长期生存的标志物。美国 FDA 于 2016 年批准 OCA 用于治疗 PBC,这导致 OCA 被纳入当前指南作为 PBC 的二线治疗药物。OCA 最具临床相关性的不良反应是剂量相关的瘙痒。我们将综述 OCA 的作用及 PBC 的当前治疗指南。