Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy.
Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy.
Eur J Intern Med. 2018 Jan;47:1-5. doi: 10.1016/j.ejim.2017.06.020. Epub 2017 Jun 29.
Primary biliary cholangitis (PBC), formerly called primary biliary cirrhosis, is a chronic cholestatic liver disease that progresses slowly to end-stage liver disease. The first Food and Drug Administration (FDA)-approved treatment for PBC was ursodeoxycholic acid (UDCA). This treatment slows the progress of the disease, but approximatively 30-40% of patients fail to respond to UDCA. A number of options are under investigation as second line treatment. Obeticholic acid (OCA), a Farnesoid X Receptor agonist, has been approved in May 2017 by FDA for patients non responders or intolerant to UDCA. The results of a randomized, double blind, phase 3 study of OCA (mg or 10mg) compared to placebo, showed that approximatively 50% of patients reached a significant reduction in serum alkaline phosphatase, a marker predictive of disease progression, liver transplantation or death. Other emerging therapies include: agents targeting fibrosis, inflammation, or immunological response. Indeed, after 30years of UDCA therapy as unique choice for PBC patients, a number of targets, derived from a deeper knowledge of the pathophysiology of the disease, has been discovered and they offer different and new therapeutic approaches that are now under evaluation.
原发性胆汁性胆管炎（PBC），以前称为原发性胆汁性肝硬化，是一种慢性胆汁淤积性肝病，缓慢进展为终末期肝病。美国食品和药物管理局（FDA）批准的第一种治疗 PBC 的药物是熊去氧胆酸（UDCA）。这种治疗可以减缓疾病的进展，但大约 30-40%的患者对 UDCA 没有反应。正在研究许多其他选择作为二线治疗。法尼醇 X 受体激动剂奥贝胆酸（OCA）于 2017 年 5 月被 FDA 批准用于对 UDCA 无反应或不耐受的患者。OCA（mg 或 10mg）与安慰剂的随机、双盲、3 期研究结果表明，大约 50%的患者血清碱性磷酸酶显著降低，碱性磷酸酶是预测疾病进展、肝移植或死亡的标志物。其他新兴疗法包括：针对纤维化、炎症或免疫反应的药物。事实上，在 UDCA 作为 PBC 患者唯一选择治疗 30 年后，许多源自对疾病病理生理学更深入了解的靶点已被发现，它们提供了不同的新的治疗方法，目前正在评估中。
