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. 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.
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.
Authors: Francesca Tavano; F Francesco di Mola; Anna Latiano; Orazio Palmieri; Fabrizio Bossa; Maria Rosa Valvano; Tiziana Latiano; Vito Annese; Angelo Andriulli; Pierluigi di Sebastiano Journal: J Crohns Colitis Date: 2011-12-13 Impact factor: 9.071
Authors: William S Mow; Eric A Vasiliauskas; Ying-Chao Lin; Phillip R Fleshner; Konstantinos A Papadakis; Kent D Taylor; Carol J Landers; Maria T Abreu-Martin; Jerome I Rotter; Huiying Yang; Stephan R Targan Journal: Gastroenterology Date: 2004-02 Impact factor: 22.682
Authors: Maria T Abreu; Kent D Taylor; Ying-Chao Lin; Tieu Hang; Joanne Gaiennie; Carol J Landers; Eric A Vasiliauskas; Lori Y Kam; Micha Rojany; Konstantinos A Papadakis; Jerome I Rotter; Stephan R Targan; Huiying Yang Journal: Gastroenterology Date: 2002-09 Impact factor: 22.682