TY - JOUR
T1 - Biomarkers for the Prediction and Diagnosis of Fibrostenosing Crohn's Disease
T2 - A Systematic Review
AU - Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium
AU - Steiner, Calen A.
AU - Berinstein, Jeffrey A.
AU - Louissaint, Jeremy
AU - Higgins, Peter D.R.
AU - Spence, Jason R.
AU - Shannon, Carol
AU - Lu, Cathy
AU - Stidham, Ryan W.
AU - Fletcher, Joel G.
AU - Bruining, David H.
AU - Feagan, Brian G.
AU - Jairath, Vipul
AU - Baker, Mark E.
AU - Bettenworth, Dominik
AU - Rieder, Florian
N1 - Publisher Copyright:
© 2022 AGA Institute
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - Biomarker
KW - Crohn's Disease
KW - Fibrosis
KW - Fibrostenosis
KW - IBD
KW - Inflammatory Bowel Disease
KW - Stenosis
KW - Stricture
UR - http://www.scopus.com/inward/record.url?scp=85114327903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114327903&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2021.05.054
DO - 10.1016/j.cgh.2021.05.054
M3 - Article
C2 - 34089850
AN - SCOPUS:85114327903
SN - 1542-3565
VL - 20
SP - 817-846.e10
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 4
ER -