在一项针对原发性硬化性胆管炎患者的辛妥珠单抗 2b 期试验中,血清细胞外基质重塑标志物与纤维化分期和预后有关。

IF 5.6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Hepatology Communications Pub Date : 2024-07-05 eCollection Date: 2024-07-01 DOI:10.1097/HC9.0000000000000467
Douglas Thorburn, Diana J Leeming, William T Barchuk, Ya Wang, Xiaomin Lu, Vladislav A Malkov, Kaori L Ito, Christopher L Bowlus, Cynthia Levy, Zachary Goodman, Morten A Karsdal, Andrew J Muir, Jun Xu
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引用次数: 0

摘要

背景:原发性硬化性胆管炎(PSC)的疾病严重程度和预后需要新的非侵入性预测指标。本研究评估了细胞外基质重塑标记物诊断纤维化阶段和预测 PSC 相关纤维化进展及临床事件的能力:方法:肝组织学和血清中的胶原形成标记物(III型胶原前肽[Pro-C3]、IV型胶原前肽、V型胶原前肽)、胶原降解标记物(III型胶原基质金属蛋白酶降解产物和IV型胶原基质金属蛋白酶降解产物)、肝纤维化[ELF]评分及其组成部分[金属蛋白酶-1、III型胶原蛋白、透明质酸])。通过逻辑回归和AUROC评估了晚期纤维化(伊萨克3-6期)和肝硬化(伊萨克5-6期)的诊断性能。通过AUROC和Wilcoxon秩和检验评估PSC相关临床事件和纤维化进展的预后效果:结果:在234名患者中,51%的患者在基线时已出现晚期纤维化,11%的患者出现肝硬化。基线Pro-C3和ELF评分及其组成部分在鉴别晚期纤维化(AUROC 0.73-0.78)和肝硬化(AUROC 0.73-0.81)方面具有中等诊断能力。基线 Pro-C3、ELF 评分和 III 型胶原蛋白对 PSC 相关临床事件的预后提供了中等程度的预测(AUROC 0.70-0.71)。在基线无肝硬化的患者中,第96周时Pro-C3和ELF评分的中位数变化在有肝硬化进展的患者中高于无肝硬化进展的患者(P均<0.001):Pro-C3与肝纤维化分期相关,Pro-C3和ELF评分可区分晚期肝纤维化和肝硬化,并预测PSC相关事件和肝纤维化进展。这些结果支持了Pro-C3和ELF评分作为PSC分期和预后标志物的临床实用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Serologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis.

Background: Novel noninvasive predictors of disease severity and prognosis in primary sclerosing cholangitis (PSC) are needed. This study evaluated the ability of extracellular matrix remodeling markers to diagnose fibrosis stage and predict PSC-related fibrosis progression and clinical events.

Methods: Liver histology and serum markers of collagen formation (propeptide of type III collagen [Pro-C3], propeptide of type IV collagen, propeptide of type V collagen), collagen degradation (type III collagen matrix metalloproteinase degradation product and type IV collagen matrix metalloproteinase degradation product), and fibrosis (enhanced liver fibrosis [ELF] score and its components [metalloproteinase-1, type III procollagen, hyaluronic acid]) were assessed in samples from baseline to week 96 in patients with PSC enrolled in a study evaluating simtuzumab (NCT01672853). Diagnostic performance for advanced fibrosis (Ishak stages 3-6) and cirrhosis (Ishak stages 5-6) was evaluated by logistic regression and AUROC. Prognostic performance for PSC-related clinical events and fibrosis progression was assessed by AUROC and Wilcoxon rank-sum test.

Results: Among 234 patients, 51% had advanced fibrosis and 11% had cirrhosis at baseline. Baseline Pro-C3 and ELF score and its components provided moderate diagnostic ability for discrimination of advanced fibrosis (AUROC 0.73-0.78) and cirrhosis (AUROC 0.73-0.81). Baseline Pro-C3, ELF score, and type III procollagen provided a moderate prognosis for PSC-related clinical events (AUROC 0.70-0.71). Among patients without cirrhosis at baseline, median changes in Pro-C3 and ELF score to week 96 were higher in those with than without progression to cirrhosis (both p < 0.001).

Conclusions: Pro-C3 correlated with fibrosis stage, and Pro-C3 and ELF score provided discrimination of advanced fibrosis and cirrhosis and predicted PSC-related events and fibrosis progression. The results support the clinical utility of Pro-C3 and ELF score for staging and as prognostic markers in PSC.

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来源期刊
Hepatology Communications
Hepatology Communications GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
8.00
自引率
2.00%
发文量
248
审稿时长
8 weeks
期刊介绍: Hepatology Communications is a peer-reviewed, online-only, open access journal for fast dissemination of high quality basic, translational, and clinical research in hepatology. Hepatology Communications maintains high standard and rigorous peer review. Because of its open access nature, authors retain the copyright to their works, all articles are immediately available and free to read and share, and it is fully compliant with funder and institutional mandates. The journal is committed to fast publication and author satisfaction. ​
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