Biomarkers for the Prediction and Diagnosis of Fibrostenosing Crohn’s Disease: A Systematic Review

• Published in: Clinical gastroenterology and hepatology Vol. 20; no. 4; pp. 817 - 846.e10
• Main Authors: Steiner, Calen A., Berinstein, Jeffrey A., Louissaint, Jeremy, Higgins, Peter D.R., Spence, Jason R., Shannon, Carol, Lu, Cathy, Stidham, Ryan W., Fletcher, Joel G., Bruining, David H., Feagan, Brian G., Jairath, Vipul, Baker, Mark E., Bettenworth, Dominik, Rieder, Florian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2022
• Subjects: Biomarker; Biomarkers; Cartilage Oligomeric Matrix Protein; Constriction, Pathologic - etiology; Crohn Disease - complications; Crohn Disease - diagnosis; Crohn Disease - pathology; Crohn’s Disease; Fibrosis; Fibrostenosis; Humans; IBD; Inflammatory Bowel Disease; Intestinal Obstruction - etiology; MicroRNAs; Serine Endopeptidases; Stenosis; Stricture; Crohn’s Disease; CD; Biomarker; IL; OR; CI; Fibrostenosis; Stenosis; GP2; IBD; Stricture; ASCA; AUC; pANCA; aPCR; SNP; ANCA; MBL; Fibrosis; TGFβ; miRNA; Inflammatory Bowel Disease
• ISSN: 1542-3565; 1542-7714
• DOI: 10.1016/j.cgh.2021.05.054

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.
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).
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.
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.
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