Tanaka Atsushi, Gershwin M Eric
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Division of Rheumatology Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, USA.
Liver Int. 2017 Apr;37(4):500-502. doi: 10.1111/liv.13344.
The introduction of ursodeoxycholic acid (UDCA)may well have contributed to some of the improvements in morbidity and mortality of primary biliary cholangitis (PBC). Yet nearly 40% of PBC patients are unresponsive to UDCA. Further the data on UDCA is confounded by the changes in the goepidemiology and particularly the earlier diagnosis of PBC. In this regard we welcome the addition of obeticholic acid (OCA) as an alternative therapeutic option forthe treatment of PBC in those patients refractory to UDCA. However, OCA is intellectually disappointing.There is no data on OCA that reflects dynamic and critical endpoints, for example death or liver transplantation; only surrogate endpoints have been used in the clinical trials. A nested study with liver histology wouldbeanideal surrogate marker,including intensive use of immunohistochemistry to define cellular infiltrates and cytokine/chemokine activity. More importantly, the clinical characteristics of PBCmay vary among patients and progression is not always predictable. We need to identify more appropriate and specific biomarkers that predict the clinical course, and we need to know which therapies are applicable at different stages, since treatmentfor PBC should be individualized. We need to know more about the etiology of PBC,and we want a cure for PBC.
熊去氧胆酸（UDCA）的引入很可能促成了原发性胆汁性胆管炎（PBC）患者发病率和死亡率的一些改善。然而，近40%的PBC患者对UDCA无反应。此外，UDCA的数据因PBC疾病流行病学的变化，特别是PBC的早期诊断而变得复杂。在这方面，我们欢迎添加奥贝胆酸（OCA）作为治疗UDCA难治性PBC患者的替代治疗选择。然而，OCA在理论上令人失望。没有关于OCA反映动态和关键终点的数据，例如死亡或肝移植；临床试验中仅使用了替代终点。一项包含肝脏组织学的巢式研究将是一个理想的替代标志物，包括大量使用免疫组织化学来定义细胞浸润和细胞因子/趋化因子活性。更重要的是，PBC的临床特征在患者中可能有所不同，且病情进展并不总是可预测的。我们需要识别出更合适、更具特异性的预测临床病程的生物标志物，并且我们需要知道在不同阶段适用哪些治疗方法，因为PBC的治疗应该个体化。我们需要更多地了解PBC的病因，并且我们希望治愈PBC。
