2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia.
2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia.
Dig Liver Dis. 2023 Oct;55(10):1318-1327. doi: 10.1016/j.dld.2022.12.010. Epub 2022 Dec 31.
Several ursodeoxycholic acid (UDCA) treatment response definitions have been introduced in primary biliary cholangitis (PBC). However, the lack of a gold standard results in heterogeneity in second-line treatment research and clinical practice.
This study aimed to explore which UDCA treatment response endpoint serves as the most accurate predictive model of long-term outcome.
A systematic review and meta-analysis of UDCA treatment response endpoints (and corresponding validations) were performed.
Sixteen individual UDCA treatment response endpoints and 96 external validations were found. Barcelona, Paris-1, Paris-2, Rotterdam, Toronto and GLOBE and UK-PBC Risk Scores are currently most robustly validated in external populations. The results show that the continuous models (GLOBE and UK-PBC Risk Scores) serve as the most accurate predictive models. Besides standard UDCA treatment response endpoints, the alkaline phosphatase and total bilirubin normalization has been suggested as a new therapeutic target.
The GLOBE and UK-PBC Risk Scores are the most suitable for the real-world allocation of second-line therapies (obeticholic acid and fibrates). However, in the wake of the recent findings, alkaline phosphatase and total bilirubin normalization should be the primary outcome in trial research in PBC.
原发性胆汁性胆管炎 (PBC) 已引入了几种熊去氧胆酸 (UDCA) 治疗反应定义。然而，由于缺乏金标准，二线治疗研究和临床实践存在异质性。
本研究旨在探讨哪种 UDCA 治疗反应终点可作为长期预后的最准确预测模型。
对 UDCA 治疗反应终点（及其相应验证）进行了系统评价和荟萃分析。
发现了 16 个单独的 UDCA 治疗反应终点和 96 个外部验证。巴塞罗那、巴黎-1、巴黎-2、鹿特丹、多伦多和 GLOBE 以及英国 PBC 风险评分目前在外部人群中得到了最有力的验证。结果表明，连续模型（GLOBE 和英国 PBC 风险评分）是最准确的预测模型。除了标准的 UDCA 治疗反应终点外，碱性磷酸酶和总胆红素正常化也被认为是新的治疗靶点。
GLOBE 和英国 PBC 风险评分最适合二线治疗（奥贝胆酸和贝特类药物）的实际分配。然而，鉴于最近的发现，碱性磷酸酶和总胆红素正常化应该成为 PBC 试验研究的主要终点。
