The Utility of Faecal Calprotectin, Lactoferrin and Other Faecal Biomarkers in Discriminating Endoscopic Activity in Crohn’s Disease: A Systematic Review and Meta-Analysis

Abstract

Introduction: Currently, faecal calprotectin (FC) is the predominate faecal biomarker utilised in clinical practice to monitor Crohn’s disease (CD) activity. However, there are several potential faecal biomarkers described in the literature. We performed a meta-analysis to determine the accuracy of faecal biomarkers in discriminating endoscopic activity and mucosal healing in CD. Methods: We searched the medical literature using MEDLINE, EMBASE, and PubMed from 1978 to 8 August 2022. Descriptive statistics, including sensitivity, specificity of the primary studies, their positive and negative likelihood ratios, and their diagnostic odds ratio (DOR), were calculated. The methodological quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS) criteria. Results: The search found 2382 studies, of which 33 were included for analysis after screening. FC was found to have a pooled sensitivity and specificity, DOR, and negative predictive value (NPV) in discriminating active endoscopic disease (versus inactive) of 81%, 74%, 13.93, and 0.27, respectively. Faecal lactoferrin (FL) had a pooled sensitivity and specificity, DOR, and NPV in discriminating active endoscopic disease of 75%, 80%, 13.41, and 0.34, respectively. FC demonstrated a pooled sensitivity and specificity, DOR, and NPV of 88%, 72%, 18.17, and 0.19 in predicting mucosal healing. Conclusion: FC remains an accurate faecal biomarker. Further evaluation of the utility of novel faecal biomarkers is needed.

The synergy of dual faecal immunochemical and faecal calprotectin testing for accurate assessment of endoscopic and histological activity in inflammatory bowel disease

“…FC is a universally established biomarker that has been extensively evaluated in both CD and UC, although the optimal cut-off values to detect endoscopic and histological activity, particularly with reference to disease location, that is, small versus large bowel segments, are not yet established. 9 , 10 FIT is a widely used marker in colorectal cancer screening worldwide with early promise in the assessment of IBD activity; however, it has yet to be incorporated into routine clinical practice in this setting.…”

“…Faecal calprotectin (FC) is a validated non-invasive measurement of IBD activity. 9 , 10 Calprotectin is a protein found predominantly in neutrophils but has also been detected in monocytes and macrophages. 11 , 12 In IBD, the inflamed intestinal mucosa results in increased permeability to migrating neutrophils, facilitating the quantitative measurement of calprotectin as a surrogate marker of intestinal inflammation in stool.…”

Crohn’s Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches

“…Fecal biomarkers, particularly FC, have emerged as crucial tools for the diagnosis and monitoring of IBD [ 11 ]. A systematic review by Bohra et al [ 12 ] (Contribution 1) evaluated the efficacy and reliability of fecal biomarkers in assessing CD by systematically reviewing and meta-analyzing the existing literature to offer clinical practice guidelines. Thirty-three studies that satisfied the inclusion criteria were reviewed, revealing FC’s accuracy in monitoring mucosal healing in CD.…”

Utility of panenteric capsule endoscopy for the detection of small‐bowel Crohn's disease in patients with a normal magnetic resonance enterography: A prospective observational pilot study

“…Diagnosis and disease activity assessments rely on ileocolonoscopy, cross-sectional imaging such as magnetic resonance enterography (MRE), and noninvasive fecal and serum biomarkers, [7][8][9][10][11] but all of these modalities have limitations in the small bowel. Ileocolonoscopy is limited to views of the distal terminal ileum 8 ; balloon enteroscopy requires technical expertise 12 ; and MRE can be poorly tolerated because of the high volumes of oral contrast and positioning requirements 13 as well as reduced sensitivity in mucosal CD.…”