原发性胆汁性胆管炎二线及后续治疗相关的临床、安全性和患者报告结局：一项系统综述。
完整摘要 · 中文译文
背景：原发性胆汁性胆管炎（PBC）是一种罕见的慢性胆汁淤积性疾病，可导致肝硬化、肝衰竭和死亡。虽然碱性磷酸酶（ALP）和总胆红素（TB）等生化标志物可衡量疾病活动度和进展，但生化应答的定义各不相同。本系统文献综述（SLR）识别了针对对熊去氧胆酸应答不足或不耐受、需要二线（2L）或更晚（2L+）治疗的PBC患者中研究性及已批准治疗的临床研究。 方法：于2025年8月7日检索电子数据库（MEDLINE；Embase），于2025年9月30日检索（Cochrane系统综述数据库；CENTRAL），并于2025年8月15日检索会议论文集（2021-2025年）、参考文献目录及ClinicalTrials.gov，遵循预先设定的方案（PROSPERO注册号：CRD42023382262）。优先纳入2L/2L+背景下的干预性和观察性研究，并提取随机对照试验数据。 结果：共纳入44项独特研究的149篇文献。III期试验评估了elafibranor、seladelpar、布地奈德、贝扎贝特和奥贝胆酸。34%的研究报告了各种复合生化应答终点，最常见的是POISE标准（18%）。生化标志物评估频繁（ALP：89%；TB：71%）；然而，正常上限和应答阈值差异很大。安慰剂对照试验中的应答率有利于积极治疗，尽管安慰剂应答高度可变。 . 16%的研究报告了无创纤维化检测指标，并显示短期内有小幅变化。患者报告结局使用多种量表评估了瘙痒（52%）和疲劳（32%）。 结论：2L/2L+ PBC治疗的证据基础广泛，但研究设计、患者人群、治疗评估量表及结局定义存在异质性，限制了跨试验比较。本系统性文献综述（SLR）为在更广泛背景下解读研究结局及支持临床决策提供了坚实基础。
完整摘要 · 英文原文
BACKGROUND: Primary biliary cholangitis (PBC) is a rare, chronic, cholestatic disease that can result in cirrhosis, liver failure, and death. While biochemical markers such as alkaline phosphatase (ALP) and total bilirubin (TB) measure disease activity and progression, definitions of biochemical response vary. This systematic literature review (SLR) identified clinical studies for investigational and approved treatments in patients with PBC with inadequate response or intolerance to ursodeoxycholic acid requiring second-line (2L) or later (2L+) therapies. METHODS: Electronic databases were searched on August 7, 2025 (MEDLINE; Embase) or September 30, 2025 (Cochrane Database of Systematic Reviews; CENTRAL), and conference proceedings (2021-2025), bibliographies, and ClinicalTrials.gov were searched on August 15, 2025, following a pre-specified protocol (PROSPERO ID: CRD42023382262). Interventional and observational studies in the 2L/2L+ setting were prioritized for inclusion, and randomized controlled trials for extraction. RESULTS: A total of 149 publications on 44 unique studies were included. Phase III trials evaluated elafibranor, seladelpar, budenoside, bezafibrate, and obeticholic acid. Various composite biochemical response endpoints were reported across 34% of studies, most frequently the POISE criteria (18%). Biochemical markers were assessed frequently (ALP: 89%; TB: 71%); however, upper limits of normal and response thresholds varied substantially. Response rates in placebo-controlled trials favored active treatment, although placebo responses were highly variable. Non-invasive fibrosis measures were reported in 16% of studies and showed small short-term changes. Patient-reported outcomes assessed pruritus (52%) and fatigue (32%) using a variety of scales. CONCLUSION: The evidence base for 2L/2L+ PBC therapies is extensive but heterogeneous in study designs, patient populations, and treatment assessment scales and outcome definitions, limiting cross-trial comparisons. This SLR provides a robust foundation for contextualizing study outcomes within the broader landscape and supporting clinical decision-making.