Retrospective Cohort Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2017; 23(41): 7387-7396
Published online Nov 7, 2017. doi: 10.3748/wjg.v23.i41.7387
Fecal calprotectin measurement is a marker of short-term clinical outcome and presence of mucosal healing in patients with inflammatory bowel disease
Athanasios Kostas, Spyros I Siakavellas, Charalambos Kosmidis, Anna Takou, Joanna Nikou, Georgios Maropoulos, John Vlachogiannakos, George V Papatheodoridis, Ioannis Papaconstantinou, Giorgos Bamias
Athanasios Kostas, Spyros I Siakavellas, Charalambos Kosmidis, John Vlachogiannakos, George V Papatheodoridis, Giorgos Bamias, Academic Department of Gastroenterology, University of Athens Medical School, Laiko General Hospital, Athens 11527, Greece
Anna Takou, Joanna Nikou, Georgios Maropoulos, Biochemistry Department, Laiko General Hospital, Athens 11527, Greece
Ioannis Papaconstantinou, 2nd Department of Surgery, University of Athens Medical School, Areteion General Hospital, Athens 11528, Greece
Author contributions: Kostas A and Siakavellas SI contributed equally to this work; Kostas A, Siakavellas SI, Papatheodoridis GV, Papaconstantinou I and Bamias G designed the research study; Takou A, Nikou J and Maropoulos G performed the laboratory tests; Kostas A, Siakavellas SI and Kosmidis C collected the data; Siakavellas SI and Bamias G analyzed the data; Kostas A, Siakavellas SI and Bamias G wrote the paper; Vlachogiannakos J, Papatheodoridis GV and Papaconstantinou I provided critical insight regarding paper preparation.
Supported by A research grant from the Hellenic Society for Gastroenterology to Bamias G.
Institutional review board statement: The study was reviewed and approved by the Laika General Hospital Ethics Committee and Institutional Review Board.
Informed consent statement: All study participants, provided informed consent for access to data in their patient files.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Giorgos Bamias, MD, PhD, Assistant Professor of Gastroenterology, Academic Department of Gastroenterology, University of Athens Medical School, Laiko General Hospital, 17 Agiou Thoma Street Athens 11527, Greece. gbamias@gmail.com
Telephone: +30-213-2061327 Fax: +30-210-7462601
Received: August 12, 2017
Peer-review started: August 19, 2017
First decision: August 30, 2017
Revised: September 18, 2017
Accepted: September 29, 2017
Article in press: September 28, 2017
Published online: November 7, 2017
Abstract
AIM

To evaluate the utility of fecal calprotectin (FC) in predicting relapse and endoscopic activity during follow-up in an inflammatory bowel disease (IBD) cohort.

METHODS

All FC measurements that were obtained during a 3-year period from patients with inflammatory bowel disease in clinical remission were identified. Data regarding the short-term (6 mo) course of the disease were extracted from the medical files. Exclusion criteria were defined as: (1) An established flare of the disease at the time of FC measurement, (2) Loss to follow up within 6 mo from baseline FC measurement, and, (3) Insufficient data on file. Statistical analysis was performed to evaluate whether baseline FC measurement could predict the short term clinical relapse and/or the presence of mucosal healing.

RESULTS

We included 149 [Crohn’s disease (CD) = 113, Ulcerative colitis (UC) = 36, male = 77] IBD patients in our study. Within the determined 6-month period post-FC measurement, 47 (31.5%) had a disease flare. Among 76 patients who underwent endoscopy, 39 (51.3%) had mucosal healing. Baseline FC concentrations were significantly higher in those who had clinical relapse compared to those who remained in remission during follow up (481.0 μg/g, 286.0-600.0 vs 89.0, 36.0-180.8, P < 0.001). The significant predictive value of baseline median with IQR FC for clinical relapse was confirmed by multivariate Cox analysis [HR for 100μg/g: 1.75 (95%CI: 1.28-2.39), P = 0.001]. Furthermore, lower FC baseline values significantly correlated to the presence of mucosal healing in endoscopy (69.0 μg/g, 30.0-128.0 vs 481.0, 278.0-600.0, in those with mucosal inflammation, median with IQR, P < 0.001). We were able to extract cut-off values for FC concentration with a high sensitivity and specificity for predicting clinical relapse (261 μg/g with AUC = 0.901, sensitivity 87.2%, specificity 85.3%, P < 0.001) or mucosal healing (174 μg/g with AUC = 0.956, sensitivity 91.9%, specificity 87.2%, P < 0.001). FC was better than CRP in predicting either outcome; nevertheless, having a pathological CRP (> 5 mg/L) in addition to the cut-offs for FC, significantly enhanced the specificity for predicting clinical relapse (95.1% from 85.3%) or endoscopic activity (100% from 87.2%).

CONCLUSION

Serial FC measurements may be useful in monitoring IBD patients in remission, as FC appears to be a reliable predictor of short-term relapse and endoscopic activity.

Keywords: Fecal calprotectin, Biomarker, Inflammatory bowel disease, Mucosal healing, Clinical outcome, Relapse, Ulcerative colitis, Crohn’s disease

Core tip: Fecal calprotectin (FC) is a novel biomarker aiming to facilitate the assessment of inflammatory bowel disease (IBD) activity as its expression is driven by the presence of intestinal inflammation. Our present retrospective study provides evidence that FC measurement during clinical remission may be helpful in identifying early those cases with a higher risk of recurrence. Moreover, lower FC values seem to correlate with endoscopic quiescence of the disease. Thus, FC monitoring may be effective in recognizing distinct subgroups of IBD patients offering the opportunity to the clinician to tailor their management accordingly in order to achieve optimal disease control.