Primary biliary cholangitis (PBC) is an enigmatic, autoimmune disease targeting the small intralobular bile ducts resulting in cholestasis and potentially progression to biliary cirrhosis. Primarily affecting middle-aged women, the diagnosis of PBC is typically straightforward with most patients presenting with cholestatic liver tests and the highly specific anti-mitochondrial antibody. For decades, the foundational treatment of PBC has been ursodeoxycholic acid (UDCA) which delays disease progression in most patients but has no impact on PBC symptoms. Large cohort studies of patients with PBC have established the benefit of maximizing the reduction in serum alkaline phosphatase with UDCA and the need to add second-line agents in patients who do not achieve an adequate response. Advances in the understanding of bile acid physiology have led to the development of new agents that improve cholestasis in patients with PBC and are predicted to reduce the risk of disease progression. Obeticholic acid, the first second-line therapy to be approved for PBC, significantly improves liver biochemistries and has been associated with improved long term clinical outcomes but is limited by its propensity to induce pruritus. Elafibranor and seladelpar are peroxisome proliferator-activated receptor agonists recently approved for use in patient with PBC, whereas bezafibrate and fenofibrate are available as off-label therapies. They also have shown biochemical improvements among patients with an inadequate response to UDCA, but may improve symptoms of pruritus. Herein, we review the patient features to consider when deciding whether a second-line agent is indicated and which agent to consider for a truly personalized approach to PBC patient care.

中文翻译：

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原发性胆汁性胆管炎：个性化二线治疗 - R1


原发性胆汁性胆管炎 （PBC） 是一种神秘的自身免疫性疾病，靶向小叶内胆管，导致胆汁淤积，并可能进展为胆汁性肝硬化。PBC 主要影响中年女性，诊断通常很简单，大多数患者表现为胆汁淤积性肝功能检查和高度特异性的抗线粒体抗体。几十年来，PBC 的基础治疗方法一直是熊去氧胆酸 （UDCA），它可以延缓大多数患者的疾病进展，但对 PBC 症状没有影响。针对 PBC 患者的大型队列研究已经确定了 UDCA 可最大限度降低血清碱性磷酸酶的益处，并且对于未达到足够反应的患者，需要添加二线药物。对胆汁酸生理学理解的进步导致了新药的开发，这些药物可以改善 PBC 患者的胆汁淤积，并有望降低疾病进展的风险。奥贝胆酸是第一个被批准用于 PBC 的二线疗法，可显著改善肝脏生化，并与改善长期临床结果有关，但受到其诱发瘙痒倾向的限制。Elafibranor 和 seladelpar 是最近被批准用于 PBC 患者的过氧化物酶体增殖物激活受体激动剂，而苯扎贝特和非诺贝特可作为超说明书疗法使用。它们还显示对 UDCA 反应不足的患者的生化改善，但可能会改善瘙痒症状。在本文中，我们回顾了在决定是否需要二线药物以及考虑哪种药物以实现真正个性化的 PBC 患者护理方法时要考虑的患者特征。