Retrospective Cohort Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Dec 31, 2019; 10(5): 54-63
Published online Dec 31, 2019. doi: 10.4291/wjgp.v10.i5.54
Fecal lactoferrin accurately reflects mucosal inflammation in inflammatory bowel disease
Marrieth G Rubio, Kofi Amo-Mensah, James M Gray, Vu Q Nguyen, Sam Nakat, Douglas Grider, Kim Love, James H Boone, Dario Sorrentino
Marrieth G Rubio, Kofi Amo-Mensah, James M Gray, Vu Q Nguyen, Dario Sorrentino, IBD Center - Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, United States
Sam Nakat, Department of Radiology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, United States
Douglas Grider, Department of Basic Science Education; Virginia Tech Carilion School of Medicine and Dominion Pathology Associates, Roanoke, VA 24016, United States
Kim Love, K. R. Love Quantitative Consulting and Collaboration, Athens, GA 30605, United States
James H Boone, Research and Development, TECHLAB Inc, Blacksburg, VA 24060, United States
Dario Sorrentino, Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, Udine 33100, Italy
Author contributions: Rubio MG contributed to the study design, participated in the data collection and analysis, and drafted the manuscript. Amo-Mensah K and Gray JM participated in data collection. Nguyen VQ contributed to the study design and participated in the analysis. Nakat S reviewed all CT and MRI images. Grider D performed the histological analyses. Love K performed the statistical analyses. Boone JH contributed to the study design and drafting of the manuscript. Sorrentino D designed and supervised the study; helped with the drafting of the manuscript and revised the final version. All the authors have read and approved the final manuscript.
Supported by an unrestricted research grant from TechLab, Blacksburg, VA, United States.
Institutional review board statement: This study was approved by The Carilion Institutional Review Board.
Informed consent statement: This retrospective study was exempted by the Carilion Institutional Board. All data was deidentified by using a unique code.
Conflict-of-interest statement: Sorrentino D has received consulting fees from Abbott/AbbVie, Schering-Plough, MSD, Janssen Research & Development, LLC., Centocor Inc., TechLab, Hoffmann-LaRoche, Giuliani, Schering-Plough, and Ferring; research grants from AbbVie, Janssen Research & Development, LLC, Schering-Plough, TechLab, Centocor, Takeda and serves in the Speakers Bureau of AbbVie and the National Faculty of Janssen. Rubio MG has received a Grant from Gilead. Nguyen VQ has received grant support from AbbVie Inc. James H Boone is a Senior Scientist at TechLab, Inc. The other authors have no conflicts of interest to declare.
Data sharing statement: No additional data is available.
STROBE statement: The authors have read the STROBE Statement and the manuscript was prepared and revised according to the STROBE Statement.
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/
Corresponding author: Dario Sorrentino, FRACP, MD, Professor, IBD Center - Division of Gastroenterology, Virginia Tech Carilion School of Medicine, 3 Riverside Circle, Roanoke, VA 24018, United States. drsorrentino@carilionclinic.org
Received: October 29, 2019
Peer-review started: October 29, 2019
First decision: November 22, 2019
Revised: December 12, 2019
Accepted: December 23, 2019
Article in press: December 23, 2019
Published online: December 31, 2019
Processing time: 61 Days and 5.3 Hours
Abstract
BACKGROUND

Studies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin (FC) and fecal lactoferrin (FL) in monitoring inflammatory bowel diseases (IBD) - Crohn’s disease (CD) and ulcerative colitis (UC). However, their correlation to endoscopic scores, disease severity and affected intestinal surface has not been extensively investigated.

AIM

To correlate FL, and for comparison white blood cell (WBC) and C-reactive protein (CRP), with endoscopic scores, disease extent and location in CD and UC.

METHODS

Retrospective analysis in 188 patients who had FL, CRP and WBC determined within 30 d of endoscopy. Disease location, disease extent (number of intestinal segments involved), disease severity (determined by endoscopic scores), timing of FL testing in relation to colonoscopy, as well as the use of effective fast acting medications (steroids and biologics) between colonoscopy and FL measurement, were recorded.

RESULTS

In 131 CD and 57 UC patients, both CRP and FL - but not WBC - distinguished disease severity (inactive, mild, moderate, severe). In patients receiving fast-acting (steroids or biologics) treatment in between FL and colonoscopy, FL showed a higher correlation to endoscopic scores when tested before vs after the procedure (r = 0.596, P < 0.001, vs r = 0.285, P = 0.15 for the Simple Endoscopic Score for CD; and r = 0.402, P = 0.01 vs r = 0.054 P = 0.84 for Disease Activity Index). Finally, FL was significantly correlated with the diseased mucosal surface (colon-ileocolon > small bowel) and the number of inflamed colon segments.

CONCLUSION

FL and CRP separated disease severity categories with FL showing lower discriminating P-values. FL showed a close correlation with the involved mucosal surface and with disease extent and was more closely correlated to endoscopy when determined before the procedure – this indicating that inflammatory activity changes associated with therapy might be rapidly reflected by FL levels. FL can accurately and timely characterize intestinal inflammation in IBD.

Keywords: Inflammatory bowel disease; Crohn’s disease; Ulcerative colitis; Fecal lactoferrin; C-reactive protein; White blood cell count; Mucosal inflammation

Core tip: Studies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin and fecal lactoferrin (FL) in monitoring Crohn’s disease (CD) and ulcerative colitis (UC). However, their correlation with disease burden (endoscopic scores/disease activity and disease extent) has not been extensively investigated. In our study FL separated disease severity categories based on endoscopic scores in both UC and CD patients. FL showed a close correlation with the diseased mucosal surface and with disease extent and was more closely correlated to endoscopy when determined before endoscopy. FL can accurately and timely represent intestinal inflammation in inflammatory bowel diseases.