纤维狭窄型克罗恩病的预测和诊断生物标志物：系统评价。
Biomarkers for the Prediction and Diagnosis of Fibrostenosing Crohn's Disease: A Systematic Review.
机构信息
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
出版信息
Clin Gastroenterol Hepatol. 2022 Apr;20(4):817-846.e10. doi: 10.1016/j.cgh.2021.05.054. Epub 2021 Jun 2.
BACKGROUND AND AIMS
Intestinal strictures are a common complication of Crohn's disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring. Herein we provide a comprehensive systematic review of studies assessing biomarkers that may predict or diagnose CD-associated strictures.
METHODS
We performed a systematic review of PubMed, EMBASE, ISI Web of Science, Cochrane Library, and Scopus to identify citations pertaining to biomarkers of intestinal fibrosis through July 6, 2020, that used a reference standard of full-thickness histopathology or cross-sectional imaging or endoscopy. Studies were categorized based on the type of biomarker they evaluated (serum, genetic, histopathologic, or fecal).
RESULTS
Thirty-five distinct biomarkers from 3 major groups were identified: serum (20 markers), genetic (9 markers), and histopathology (6 markers). Promising markers include cartilage oligomeric matrix protein, hepatocyte growth factor activator, and lower levels of microRNA-19-3p (area under the curves were 0.805, 0.738, and 0.67, respectively), and multiple anti-flagellin antibodies (A4-Fla2 [odds ratio, 3.41], anti Fla-X [odds ratio, 2.95], and anti-CBir1 [multiple]). Substantial heterogeneity was observed and none of the markers had undergone formal validation. Specific limitations to acceptance of these markers included failure to use a standardized definition of stricturing disease, lack of specificity, and insufficient relevance to the pathogenesis of intestinal strictures or incomplete knowledge regarding their operating properties.
CONCLUSIONS
There is a lack of well-defined studies on biomarkers of intestinal stricture. Development of reliable and accurate biomarkers of stricture is a research priority. Biomarkers can support the clinical management of CD patients and aid in the stratification and monitoring of patients during clinical trials of future antifibrotic drug candidates.
背景与目的
肠狭窄是克罗恩病（CD）的常见并发症。肠狭窄的生物标志物有助于预测、诊断和监测。本文对评估可能预测或诊断 CD 相关狭窄的生物标志物的研究进行了全面的系统评价。
方法
我们对 PubMed、EMBASE、ISI Web of Science、Cochrane 图书馆和 Scopus 进行了系统评价，以确定截至 2020 年 7 月 6 日与肠纤维化生物标志物相关的参考文献，这些参考文献使用全层组织病理学或横断面成像或内镜检查作为参考标准。研究根据评估的生物标志物类型进行分类（血清、遗传、组织病理学或粪便）。
结果
从 3 个主要组中确定了 35 种不同的生物标志物：血清（20 种标志物）、遗传（9 种标志物）和组织病理学（6 种标志物）。有前途的标志物包括软骨寡聚基质蛋白、肝细胞生长因子激活剂和较低水平的 microRNA-19-3p（曲线下面积分别为 0.805、0.738 和 0.67），以及多种抗鞭毛蛋白抗体（A4-Fla2[比值比，3.41]、抗 Fla-X[比值比，2.95]和抗-CBir1[多重]）。观察到存在大量异质性，并且没有一种标志物经过正式验证。这些标志物的接受存在特定的局限性，包括未能使用狭窄疾病的标准化定义、特异性不足以及与肠狭窄的发病机制相关性不足或对其作用特性的了解不完整。
结论
肠狭窄的生物标志物缺乏明确的研究。开发可靠和准确的狭窄生物标志物是一项研究重点。生物标志物可以支持 CD 患者的临床管理，并有助于在未来抗纤维化药物候选物的临床试验中对患者进行分层和监测。
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