- Fecal Incontinence
|Biomarkers for the Prediction and Diagnosis of Fibrostenosing Crohn's disease: A Systematic Review
Clin Gastroenterol Hepatol. 2021 Jun 2;S1542-3565(21)00593-0. doi: 10.1016/j.cgh.2021.05.054.Online ahead of print.
Calen A Steiner 1, Jeffrey A Berinstein 2, Jeremy Louissaint 2, Peter D R Higgins 2, Jason R Spence 3, Carol Shannon 4, Cathy Lu 5, Ryan W Stidham 6, Joel G Fletcher 7, David H Bruining 8, Brian G Feagan 9, Vipul Jairath 9, Mark E Baker 10, Dominik Bettenworth 11, Florian Rieder 12, Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium
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 and/or cross-sectional imaging and/or endoscopy. Studies were categorized based upon the type of biomarker they evaluated (serum, genetic, histopathologic, or fecal).
Results: Thirty-five distinct biomarkers from three 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 (AUC 0.805, 0.738 and 0.67 respectively), and multiple anti-flagellin antibodies (A4-Fla2 [OR 3.41], anti Fla-X [OR 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.