Primary biliary cholangitis is a chronic, seropositive and female-predominant inflammatory and cholestatic liver disease, which has a variable rate of progression towards biliary cirrhosis. Substantial progress has been made in patient risk stratification with the goal of personalized care, including early adoption of next-generation therapy with licensed use of obeticholic acid or off-label fibrate derivatives for those with insufficient benefit from ursodeoxycholic acid, the current first-line drug. The disease biology spans genetic risk, epigenetic changes, dysregulated mucosal immunity and altered biliary epithelial cell function, all of which interact and arise in the context of ill-defined environmental triggers. A current focus of research on nuclear receptor pathway modulation that specifically and potently improves biliary excretion, reduces inflammation and attenuates fibrosis is redefining therapy. Patients are benefiting from pharmacological agonists of farnesoid X receptor and peroxisome proliferator-activated receptors. Immunotherapy remains a challenge, with a lack of target definition, pleiotropic immune pathways and an interplay between hepatic immune responses and cholestasis, wherein bile acid-induced inflammation and fibrosis are dominant clinically. The management of patient symptoms, particularly pruritus, is a notable goal reflected in the development of rational therapy with apical sodium-dependent bile acid transporter inhibitors.

中文翻译：

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原发性胆源性胆管炎：发病机理和治疗机会。

原发性胆源性胆管炎是一种慢性，血清反应阳性，女性为主的炎性和胆汁淤积性肝病，其进展为胆汁性肝硬化的速度各异。以个性化护理为目标，在患者风险分层方面已取得了实质性进展，其中包括早期采用下一代治疗方法，即许可使用奥贝胆酸或标签外的贝特类药物衍生物治疗那些目前尚不能从熊去氧胆酸中获益的患者药品。疾病生物学涉及遗传风险，表观遗传学变化，粘膜免疫功能失调和胆道上皮细胞功能改变，所有这些相互作用都是在不确定的环境触发条件下发生的。当前对核受体途径调节的研究重点是特异性和有效地改善胆汁排泄，减轻炎症和减轻纤维化是重新定义的治疗方法。患者受益于法呢类X受体和过氧化物酶体增殖物激活受体的药理激动剂。免疫疗法仍然是一个挑战，缺乏目标定义，多效性免疫途径以及肝免疫反应和胆汁淤积之间的相互作用，其中胆汁酸诱导的炎症和纤维化在临床上占主导地位。对患者症状，特别是瘙痒的处理，是通过根尖钠依赖性胆汁酸转运蛋白抑制剂进行合理治疗的一个显着目标。缺乏靶标定义，多效性免疫途径以及肝免疫反应和胆汁淤积之间的相互作用，其中胆汁酸诱导的炎症和纤维化在临床上占主导地位。对患者症状，特别是瘙痒的处理，是通过根尖钠依赖性胆汁酸转运蛋白抑制剂进行合理治疗的一个显着目标。缺乏靶标定义，多效性免疫途径以及肝免疫反应和胆汁淤积之间的相互作用，其中胆汁酸诱导的炎症和纤维化在临床上占主导地位。对患者症状，特别是瘙痒的处理，是通过根尖钠依赖性胆汁酸转运蛋白抑制剂进行合理治疗的一个显着目标。