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:
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.
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
Research background

Currently, there is increased need for the discovery of simple to perform, non-invasive biomarkers with high correlation to intestinal inflammatory activity in patients with inflammatory bowel disease (IBD). Fecal calprotectin (FC) measurement has shown promise as a candidate marker for this purpose.

Research motivation

Although the value of measuring FC as an indicator for active inflammation is indisputable, the correlation between FC values and future flare of disease activity has not been fully established. Furthermore, uncertainty still exists regarding the optimal cut-off values of FC for this indication and applicability of its measurement in diverse patient groups.

Research objectives

Our principal aim was to study the clinical significance of measuring FC in IBD patients in clinical remission, both as a biomarker for patients stratification according to their risk for relapse, as well as a surrogate marker of endoscopic mucosal healing.

Research methods

We retrospectively analyzed the electronic medical records of all patients with IBD, with a regular follow up at our department and a FC measurement in a 3-year study period. We specifically focused on patients in stable clinical remission and a medium-term follow-up (at least 6-mo). We then compared two groups of patients: those who remained in remission and those who relapsed (according to pre-defined criteria) during the 6-mo follow-up. A secondary aim of our study was to examine whether the measured FC value could predict the presence or absence of mucosal healing (defined as an endoscopic Mayo Score of 0 for UC and absence of significant mucosal lesions in the colon and terminal ileum for CD, respectively). For all study participants, demographic, epidemiologic and clinical data were retrieved from the patient files and entered in an SPSS database.

Research results

The main findings of our analysis are as follows: First, patients who relapsed within 6-mo from FC measurement had significantly higher baseline FC concentrations than those who remained in remission. Second, patients with mucosal abnormalities in endoscopy (i.e. absence of mucosal healing) had significantly higher FC values as compared to patients that demonstrated endoscopic mucosal healing. Third, we were able to define cut-off values for FC concentrations with high sensitivity and specificity for predicting clinical relapse or endoscopical activity in patients with IBD in clinical remission. Fourth, combining FC with CRP measurements further increases the predictive value for short-term clinical flare. Finally, cut-offs may be significantly lower in patients with post-surgical recurrence of CD in comparison to surgery-free patients.

Research conclusions

Our findings clearly indicate that short-term clinical relapse can be predicted with high accuracy by measuring FC concentration in patients with IBD. Consequently, serial FC measurements may prove to be a very useful tool to monitor subclinical inflammatory activity in IBD patients who are in clinical remission. Furthermore, our results show that a high FC value is a surrogate marker of endoscopically active disease. Given the high importance that mucosal healing has gained in recent years for determining disease outcomes in IBD, FC measurements may become a valuable tool for the selection of those patients who need to have an endoscopy while in clinical remission. Subsequently, treatment modifications may be preemptively implemented in such cases, in order to avoid clinical recurrence of symptoms and the systemic consequences of persisting inflammatory activity.