Department of Biomedical Sciences, Humanitas University, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano, Italy.
Department of Infectious Diseases and Center for Liver Diseases, Peking University First Hospital, Beijing, China; Department of Infectious Diseases and Liver Diseases, Peking University International Hospital, Beijing, China.
Lancet. 2020 Dec 12;396(10266):1915-1926. doi: 10.1016/S0140-6736(20)31607-X.
Primary biliary cholangitis is an autoimmune liver disease that predominantly affects women. It is characterised by a chronic and destructive, small bile duct, granulomatous lymphocytic cholangitis, with typical seroreactivity for antimitochondrial antibodies. Patients have variable risks of progressive ductopenia, cholestasis, and biliary fibrosis. Considerations for the cause of this disease emphasise an interaction of chronic immune damage with biliary epithelial cell responses and encompass complex, poorly understood genetic risks and environmental triggers. Licensed disease-modifying treatment focuses on amelioration of cholestasis, with weight-dosed oral ursodeoxycholic acid. For patients who do not respond sufficiently, or patients with ursodeoxycholic acid intolerance, conditionally licensed add-on therapy is with the FXR (NR1H4) agonist, obeticholic acid. Off-label therapy is recognised as an alternative, notably with the pan-PPAR agonist bezafibrate; clinical trial agents are also under development. Baseline characteristics, such as young age, male sex, and advanced disease, and serum markers of liver injury, particularly bilirubin and ALP, are used to stratify risk and assess treatment responsiveness. Parallel attention to the burden of patient symptoms is paramount, including pruritus and fatigue.
原发性胆汁性胆管炎是一种主要影响女性的自身免疫性肝病。其特征为慢性、破坏性小胆管、肉芽肿性淋巴细胞性胆管炎,伴有抗线粒体抗体的典型血清反应性。患者有进行性胆管减少、胆汁淤积和胆管纤维化的不同风险。对这种疾病病因的考虑强调了慢性免疫损伤与胆管上皮细胞反应的相互作用,并包含了复杂、尚未完全理解的遗传风险和环境触发因素。经过许可的疾病修饰治疗侧重于改善胆汁淤积,使用剂量依赖性口服熊去氧胆酸。对于那些反应不足的患者,或对熊去氧胆酸不耐受的患者,可以有条件地添加 FXR(NR1H4)激动剂,奥贝胆酸。非适应证治疗被认为是一种替代方法,特别是使用全过氧化物酶体增殖物激活受体激动剂贝扎贝特;临床试验药物也在开发中。基线特征,如年龄较小、男性、疾病晚期,以及肝脏损伤的血清标志物,特别是胆红素和碱性磷酸酶,用于分层风险和评估治疗反应。同时关注患者症状的负担至关重要,包括瘙痒和疲劳。