Prospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2017; 23(46): 8235-8247
Published online Dec 14, 2017. doi: 10.3748/wjg.v23.i46.8235
Efficacy of noninvasive evaluations in monitoring inflammatory bowel disease activity: A prospective study in China
Jin-Min Chen, Tao Liu, Shan Gao, Xu-Dong Tong, Fei-Hong Deng, Biao Nie
Jin-Min Chen, Shan Gao, Xu-Dong Tong, Department of Gastroenterology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
Tao Liu, Department of Gastroenterology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510665, Guangdong Province, China
Fei-Hong Deng, Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Biao Nie, Department of Gastroenterology, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510630, Guangdong Province, China
Author contributions: Chen JM and Nie B designed the study and wrote the manuscript; Deng FH collected fecal and blood samples and completed patient case report; Liu T and Nie B performed all endoscopies and completed the endoscopic scoring sheet; Tong XD quantified fecal calprotectin; Gao S performed data analysis; all authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China to Biao Nie, No. 81471080.
Institutional review board statement: The study was reviewed and approved by the institutional review board of Department of Gastroenterology in Nanfang Hospital (Guangzhou, China) and the Medical Ethnic Committee of Nanfang Hospital (NFEC-2014-065).
Clinical trial registration statement: The clinical trial was registered in Chinese Clinical Trial Registry (registration ID: ChiCTR-DDT-14005066). Details can be found at http://www.chictr.org.cn/showproj.aspx?proj=4509.
Informed consent statement: All study participants provided written informed consent prior to study enrollment.
Conflict-of-interest statement: The authors of this manuscript have no conflicts of interest to disclose.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at email: niebiao2@163.com. Participants gave informed consent for data sharing.
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: Biao Nie, MD, PhD, Professor, Associate Chief Physician, Department of Gastroenterology, the First Affiliated Hospital of Jinan University, Jinan University, No. 614, West Huangpu Avenue, Guangzhou 510630, Guangdong Province, China. niebiao2@163.com
Telephone: +86-15101503392 Fax: +86-20-38688025
Received: July 31, 2017
Peer-review started: August 1, 2017
First decision: September 6, 2017
Revised: September 28, 2017
Accepted: November 2, 2017
Article in press: November 2, 2017
Published online: December 14, 2017
Processing time: 134 Days and 4.7 Hours
ARTICLE HIGHLIGHTS
Research background

Inflammatory bowel disease (IBD) is characterized by periods of relapsing-remitting. At present, most clinicians monitor IBD activity and guide therapeutic decisions based on clinical activity indexes. However, emerging data show that clinical assessment indexes correlate poorly with endoscopic activity and IBD patients with clinically quiescent disease may still have residual mucosal inflammation. An endoscopic procedure is considered the gold standard for assessing disease activity. However, the endoscopy is invasive, uncomfortable, and expensive.

Research motivation

A simple, acceptable, and specific evaluation is needed to play an adjunctive role in the assessment of IBD activity. The specific and noninvasive evaluation could instruct clinicians to timely choose reasonable therapy regimen and predict prognosis. Furthermore, a new evaluation that can detect increased disease activity earlier before any clinical symptoms have occurred could change disease course, enabling the most cost-effective use of medical resources.

Research objectives

The main objective of this study was to assess the efficacy of noninvasive evaluations for the disease activity in colonic or ileo-colonic Crohn’s disease (CICD), CD-related surgery, and ulcerative colitis (UC) patients and further to optimize the accuracy of those noninvasive evaluations in detecting active residual mucosal inflammation in IBD patients in clinical remission. In our study we confirmed the efficacy of fecal calprotectin (FC) and the new clinical FC activity (CFA) in assessing disease activity in CICD and UC patients. In future, clinicians and researchers could use FC to recognize an imminent endoscopic flare. What’s more, FC could be measured frequently as a clinical activity index to detect preclinical mucosal inflammation in clinical remission patients.

Research methods

In total, 136 consecutive IBD patients and 25 recruited IBS patients were enrolled. For all IBD patients, the day before the endoscopy, fecal and blood samples were collected to measure FC, CRP, ESR, and PCT. At the same time, the patients were asked to complete a case report to calculate their clinical activity index (CDAI/CAI). Then, endoscopic activity was determined for CICD patients with the “simple endoscopic score for Crohn’s disease” (SES-CD), CD-related surgery patients with the Rutgeerts score, and UC patients with the Mayo score. The efficacies of these evaluations to predict the endoscopic activity were assessed by Mann-Whitney test, χ2 test, Spearman’s correlation, and multiple linear regression analysis. In our study, multiple linear regression analysis with stepwise deletion was performed based on FC, CDAI/CAI, CRP, ESR, and PCT to construct a combined score, clinical FC activity (CFA), which could best predict the endoscopy activity. In clinical scenario, clinicians could identify endoscopic active disease more accurately with CFA through a short inquiry and a FC test.

Research results

We found that FC and clinical FC activity (CFA) are useful, non-invasive, and sensitive stool markers for gut inflammation in both CICD and UC patients. However, the standard collection of fecal sample and best cutoff to predict endoscopic activity are needed to be solved.

Research conclusions

This was the first study performed in China for disease activity analysis in the three groups of IBD patients separately. We also constructed a clinical FC activity (CFA) index to more accurately assess disease activity. Moreover, we found that FC had ability to detect active residual mucosal inflammation in IBD patients in clinical remission. Indeed, we also found that IBD patients in endoscopic remission still had significantly higher levels of FC when compared with IBS patients. A high level of FC could be a reliable marker of persistent active microscopic inflammation. Then FC remission may indicate deep remission at histopathology level, which was proven to be a strong predictor of favorable prognosis in IBD. In future, the next step is to use FC to guide the clinicians to adjust the treatment regimen. We can schedule regular FC measurement and compare the change from baseline level to reflect the degree of response to treatment.

Research perspectives

In our study, we confirmed the efficacy of FC in assessing disease activity in IBD patients. In future, we recommend periodic FC measurements instead of a single measurement in monitoring disease activity and deciding the treatment regimen. The clinical remission and biomarker healing could be the new therapeutic goals in IBD patients. To achieve those goals, multicenter, large-sample, randomized clinical trials are warranted to prove their value in clinical practice.