The challenges of primary biliary cholangitis: What is new and what needs to be done
The challenges of primary biliary cholangitis: What is new and what needs to be done
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DOI：
10.1016/j.jaut.2019.102328
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发表时间：
2019-12-01
影响因子：
12.8
通讯作者：
Gershwin, M. Eric
中科院分区：
文献类型：
--
作者：
Benedetta, Terziroli Beretta-Piccoli;Mieli-Vergani, Giorgina;Gershwin, M. Eric
原发性胆汁性胆管炎（PBC）是一种不常见的慢性自身免疫性胆管病，其病因不明，其特征是抗线粒体自身抗体（AMA）阳性，女性占优势，如果不治疗则进展为肝硬化。诊断是基于AMA-或PBC-特异性抗核抗体（ANA）阳性，在胆汁淤积的生化特征的存在下，组织学确认是强制性的，只有在血清阴性的情况下。一线治疗是熊去氧胆酸（UDCA），可有效预防约三分之二患者的疾病进展。本文总结了2018年9月23日至25日在瑞士卢加诺举行的一次会议的最相关结论，该会议聚集了来自世界各地具有各种背景的基础和临床科学家，讨论PBC研究的最新进展。该会议是专门为伊恩麦凯，在自身免疫性肝病领域的先驱。肝脏组织学的作用需要重新考虑：越来越多的报道表明，在没有生化胆汁淤积的AMA阳性个体中，肝脏病理学与PBC一致，这就提出了生化胆汁淤积是否是临床实践和试验的可靠疾病标志物的问题。会议期间还广泛讨论了迫切需要新的生物标志物，包括更准确的胆汁淤积标志物。此外，对PBC中胆汁酸与胆管上皮相互作用的新见解提供了确凿的证据，证明上皮保护受损对潜在有毒的疏水性胆汁酸的作用，提出了一个根本问题：胆汁酸诱导的上皮损伤是原因还是结果自身免疫性攻击胆管上皮。需要在疾病早期阶段识别难以治疗的患者，此时除了基于胆汁酸的治疗之外，针对免疫途径的新治疗方法可能有效。总之，使用跨学科的方法，突破性的进展，可以预期不久就在我们的理解PBC的发病机制，最终目的是改善其治疗。
Primary Biliary Cholangitis (PBC) is an uncommon, chronic, cholangiopathy of autoimmune origin and unknown etiology characterized by positive anti-mitochondrial autoantibodies (AMA), female preponderance and progression to cirrhosis if left untreated. The diagnosis is based on AMA- or PBC-specific anti-nuclear antibody (ANA)-positivity in the presence of a cholestatic biochemical profile, histologic confirmation being mandatory only in seronegative cases. First-line treatment is ursodeoxycholic acid (UDCA), which is effective in preventing disease progression in about two thirds of the patients. The only approved second-line treatment is obeticholic acid.This article summarizes the most relevant conclusions of a meeting held in Lugano, Switzerland, from September 23rd-25th 2018, gathering basic and clinical scientists with various background from around the world to discuss the latest advances in PBC research. The meeting was dedicated to Ian Mackay, pioneer in the field of autoimmune liver diseases. The role of liver histology needs to be reconsidered: liver pathology consistent with PBC in AMA-positive individuals without biochemical cholestasis is increasingly reported, raising the question as to whether biochemical cholestasis is a reliable disease marker for both clinical practice and trials. The urgent need for new biomarkers, including more accurate markers of cholestasis, was also widely discussed during the meeting. Moreover, new insights in interactions of bile acids with biliary epithelia in PBC provide solid evidence of a role for impaired epithelial protection against potentially toxic hydrophobic bile acids, raising the fundamental question as to whether this bile acid-induced epithelial damage is the cause or the consequence of the autoimmune attack to the biliary epithelium. Strategies are needed to identify difficult-totreat patients at an early disease stage, when new therapeutic approaches targeting immunologic pathways, in addition to bile acid-based therapies, may be effective. In conclusion, using interdisciplinary approaches, groundbreaking advances can be expected before long in respect to our understanding of the etiopathogenesis of PBC, with the ultimate aim of improving its treatment.