Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid with an established benefit for patients suffering from primary biliary cholangitis (PBC). It was first introduced in the 60s and took until the late 90s to demonstrate a survival benefit in large meta-cohort studies.1 Since then, UDCA is the established first-line therapy according to current guidelines.2 The benefit of UDCA is multidimensional, and patients receiving UDCA experience increased transplant-free survival, a decreased risk of hepatocellular carcinoma and potentially improved quality of life.3–5 The survival benefit is predicted by a number biochemical markers that reflect cholestasis and that are accepted surrogates of the treatment response—a fact that has accelerated drug development and approval. Interestingly, even patients who are considered incomplete responders to UDCA—characterised by persistently elevated alkaline phosphates levels (ALPs) or abnormal bilirubin—a survival benefit compared with patients that are not on UDCA can be detected.4 The mechanism by which UDCA mediates these effects are numerous and involve: (1) protection of chonlangiocytes from cytotoxic hydrophobic bile acids, (2) increased hepatobiliary secretion of bile components and (3) protection of hepatocytes from bile acid-induced apoptosis. UDCA enrichment in the bile is linear to the administered dose and thus a sufficient dose—typically ranging between 13 mg/kg and 15 mg/kg bodyweight—is required to achieve therapeutic efficacy. The safety profile of UDCA is positive with only few patients experiencing dyspepsia, lose stools or mild diarrhoea. Therefore, all patients diagnosed with PBC according to current criteria should be started on UDCA as primary treatment immediately. More recently, second-line therapies—including bezafibrate and the steroidal FXR-agonist obeticholic acid (OCA)—have been trialled in …

中文翻译：

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使用熊去氧胆酸预防原发性胆汁性胆管炎的终点：量化益处

熊去氧胆酸 (UDCA) 是一种亲水性胆汁酸，对患有原发性胆汁性胆管炎 (PBC) 的患者具有既定益处。它于 60 年代首次推出，直到 90 年代后期才在大型荟萃队列研究中证明了生存获益。1 从那时起，UDCA 是根据当前指南确定的一线治疗。2 UDCA 的益处是多方面的，接受 UDCA 的患者经历了无移植生存率的提高、肝细胞癌风险的降低和生活质量的潜在改善。 3-5 生存获益是通过许多反映胆汁淤积的生化标志物来预测的，这些标志物是治疗反应的公认替代指标——这一事实加速了药物的开发和批准。有趣的是，即使被认为对 UDCA 反应不完全的患者——其特征是碱性磷酸盐水平 (ALP) 持续升高或胆红素异常——与未使用 UDCA 的患者相比，也可以检测到生存获益。 4 UDCA 介导这些作用的机制有很多包括：（1）保护软骨细胞免受细胞毒性疏水性胆汁酸的影响，（2）增加胆汁成分的肝胆分泌和（3）保护肝细胞免受胆汁酸诱导的细胞凋亡。胆汁中 UDCA 的富集与给药剂量呈线性关系，因此需要足够的剂量——通常在 13 mg/kg 至 15 mg/kg 体重之间——才能达到治疗效果。UDCA 的安全性是积极的，只有少数患者出现消化不良、排便或轻度腹泻。所以，根据现行标准诊断为 PBC 的所有患者应立即开始使用 UDCA 作为主要治疗。最近，包括苯扎贝特和甾体 FXR 激动剂奥贝胆酸 (OCA) 在内的二线疗法已在……