Abstract

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

 
     

Author information

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

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 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.

 

© Copyright 2013-2022 GI Health Foundation. All rights reserved.
This site is maintained as an educational resource for US healthcare providers only. Use of this website is governed by the GIHF terms of use and privacy statement.