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.