Department of Internal Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Hepatology. 2020 Sep;72(3):1127-1138. doi: 10.1002/hep.31311.
The pathogenesis of primary sclerosing cholangitis (PSC), a progressive biliary tract disease without approved medical therapy, is not well understood. The relationship between PSC and inflammatory bowel disease has inspired theories that intestinal factors may contribute to the development and progression of hepatobiliary fibrosis in PSC. There is evidence from both fecal and mucosa-associated microbial studies that patients with PSC harbor an abnormal enteric microbiome. These organisms are thought to produce toxic byproducts that stimulate immune-mediated damage of hepatocytes and the biliary tree. The link between these mechanisms may be related to altered intestinal permeability leading to migration of bacteria or associated toxins to the liver through the portal circulation. In support of these concepts, early trials have demonstrated improved biochemical parameters and symptoms of PSC with oral antibiotics, ostensibly through manipulation of the enteric microbiota. This article reviews the published literature for evidence as well as gaps in knowledge regarding these mechanisms by which intestinal aberrations might drive the development of PSC. We also identify areas of future research that are needed to link and verify these pathways to enhance diagnostic and therapeutic approaches.
原发性硬化性胆管炎（PSC）是一种进行性胆道疾病，目前尚无批准的治疗方法，其发病机制尚不清楚。PSC 与炎症性肠病之间的关系激发了这样一种理论，即肠道因素可能有助于 PSC 中肝胆纤维化的发展和进展。粪便和黏膜相关微生物研究都有证据表明，PSC 患者存在异常的肠道微生物组。这些生物体被认为会产生有毒的副产物，刺激免疫介导的肝细胞和胆管损伤。这些机制之间的联系可能与改变的肠道通透性有关，导致细菌或相关毒素通过门脉循环迁移到肝脏。这些概念得到了早期试验的支持，这些试验表明口服抗生素可改善 PSC 的生化参数和症状，表面上是通过肠道微生物群的操纵。本文综述了已发表的文献，以了解肠道异常如何驱动 PSC 发展的这些机制的证据和知识空白。我们还确定了未来需要研究的领域，以联系和验证这些途径，从而增强诊断和治疗方法。
