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

Calen A Steiner; Jeffrey A Berinstein; Jeremy Louissaint; Peter D R Higgins; Jason R Spence; Carol Shannon; Cathy Lu; Ryan W Stidham; Joel G Fletcher; David H Bruining; Brian G Feagan; Vipul Jairath; Mark E Baker; Dominik Bettenworth; Florian Rieder; Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium

doi:10.1016/j.cgh.2021.05.054

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

Clin Gastroenterol Hepatol. 2022 Apr;20(4):817-846.e10. doi: 10.1016/j.cgh.2021.05.054. Epub 2021 Jun 2.

Authors

Calen A Steiner¹, Jeffrey A Berinstein², Jeremy Louissaint², Peter D R Higgins², Jason R Spence³, Carol Shannon⁴, Cathy Lu⁵, Ryan W Stidham⁶, Joel G Fletcher⁷, David H Bruining⁸, Brian G Feagan⁹, Vipul Jairath⁹, Mark E Baker¹⁰, Dominik Bettenworth¹¹, Florian Rieder¹²; Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium

Affiliations

¹ Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. Electronic address: calen.steiner@cuanschutz.edu.
² Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
³ Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan.
⁴ Taubman Health Sciences Library, University of Michigan, Ann Arbor, Michigan.
⁵ Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
⁶ Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan.
⁷ Department of Radiology, Mayo Clinic, Rochester, Minnesota.
⁸ Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
⁹ Alimentiv Inc, London, Ontario, Canada; Department of Medicine, Western University, London, Ontario, Canada; Department of Biostatistics and Epidemiology, Western University, London, Ontario, Canada.
¹⁰ Section of Abdominal Imaging, Imaging Institute, Digestive Diseases and Surgery Institute and Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
¹¹ Department of Medicine B, Gastroenterology and Hepatology, University of Münster, Münster, Germany.
¹² Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio; Department of Gastroenterology, Hepatology, and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic Foundation, Cleveland, Ohio.

Abstract

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.

Keywords: Biomarker; Crohn’s Disease; Fibrosis; Fibrostenosis; IBD; Inflammatory Bowel Disease; Stenosis; Stricture.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Biomarkers
Cartilage Oligomeric Matrix Protein
Constriction, Pathologic / etiology
Crohn Disease* / complications
Crohn Disease* / diagnosis
Crohn Disease* / pathology
Humans
Intestinal Obstruction* / etiology
MicroRNAs*
Serine Endopeptidases

Substances

Biomarkers
Cartilage Oligomeric Matrix Protein
MIRN19 microRNA, human
MicroRNAs
HGF activator
Serine Endopeptidases

Abstract

Publication types

MeSH terms

Substances

Grants and funding