NIHR Birmingham Biomedical Research Centre, Birmingham, UK.
University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Gut. 2018 Sep;67(9):1568-1594. doi: 10.1136/gutjnl-2017-315259. Epub 2018 Mar 28.
Primary biliary cholangitis (formerly known as primary biliary cirrhosis, PBC) is an autoimmune liver disease in which a cycle of immune mediated biliary epithelial cell injury, cholestasis and progressive fibrosis can culminate over time in an end-stage biliary cirrhosis. Both genetic and environmental influences are presumed relevant to disease initiation. PBC is most prevalent in women and those over the age of 50, but a spectrum of disease is recognised in adult patients globally; male sex, younger age at onset (<45) and advanced disease at presentation are baseline predictors of poorer outcome. As the disease is increasingly diagnosed through the combination of cholestatic serum liver tests and the presence of antimitochondrial antibodies, most presenting patients are not cirrhotic and the term cholangitis is more accurate. Disease course is frequently accompanied by symptoms that can be burdensome for patients, and management of patients with PBC must address, in a life-long manner, both disease progression and symptom burden. Licensed therapies include ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), alongside experimental new and re-purposed agents. Disease management focuses on initiation of UDCA for all patients and risk stratification based on baseline and on-treatment factors, including in particular the response to treatment. Those intolerant of treatment with UDCA or those with high-risk disease as evidenced by UDCA treatment failure (frequently reflected in trial and clinical practice as an alkaline phosphatase >1.67 × upper limit of normal and/or elevated bilirubin) should be considered for second-line therapy, of which OCA is the only currently licensed National Institute for Health and Care Excellence recommended agent. Follow-up of patients is life-long and must address treatment of the disease and management of associated symptoms.
原发性胆汁性胆管炎(以前称为原发性胆汁性肝硬化,PBC)是一种自身免疫性肝病,其中免疫介导的胆管上皮细胞损伤、胆汁淤积和进行性纤维化的循环可随时间推移导致终末期胆汁性肝硬化。遗传和环境因素都被认为与疾病的发生有关。PBC 在女性和 50 岁以上人群中更为常见,但在全球成年患者中,疾病谱广泛存在;男性、发病年龄较小(<45 岁)和就诊时疾病较严重是预后较差的基线预测因素。随着该疾病通过胆汁淤积性血清肝功能检查和存在抗线粒体抗体的联合诊断越来越多,大多数就诊患者并非肝硬化,因此使用“胆管炎”一词更为准确。疾病过程常伴有可使患者感到不适的症状,因此 PBC 患者的管理必须长期考虑疾病进展和症状负担。已批准的治疗方法包括熊去氧胆酸(UDCA)和奥贝胆酸(OCA),以及新的和重新利用的实验性药物。疾病管理侧重于为所有患者启动 UDCA 治疗,并根据基线和治疗期间的因素(包括尤其是对治疗的反应)进行风险分层。对于不耐受 UDCA 治疗或具有高危疾病的患者(证据通常反映在试验和临床实践中,碱性磷酸酶>1.67×正常值上限和/或胆红素升高),应考虑二线治疗,其中 OCA 是唯一目前获得国家卫生与保健卓越研究所批准的推荐药物。患者的随访是终身的,必须解决疾病的治疗和相关症状的管理。