Alimentary Tract
Accuracy of fecal calprotectin for the prediction of endoscopic activity in patients with inflammatory bowel disease

https://doi.org/10.1016/j.dld.2017.12.022Get rights and content

Abstract

Background

Fecal calprotectin is a noninvasive marker of inflammatory bowel disease.

Aim

To evaluate the accuracy of calprotectin for prediction of endoscopic activity in inflammatory bowel disease.

Methods

One-hundred patients were prospectively included. Quantum Blue® (Bühlmann) kits were used to determine calprotectin. Endoscopic activity was calculated. Various serum markers (platelets, leukocytes, C-reactive protein, and albumin) were recorded.

Results

Calprotectin was higher in patients with endoscopic activity than in those without activity: in ulcerative colitis, with the low- (29 ± 14 vs. 301 ± 174, p < 0.001) and high- (99 ± 727 vs. 617 ± 801, p < 0.001); and in Crohn’s disease, with the low- (29 ± 59 vs. 124 ± 268, p < 0.01) and high-range kit (99 ± 37 vs. 287 ± 607, p < 0.01). Serological marker concentrations did not vary with endoscopic activity. The area under the ROC curve of calprotectin for the prediction of endoscopic activity was 0.9 in ulcerative colitis and 0.8 in Crohn’s disease. The best cut-off points for the detection of activity in ulcerative colitis were 50 for the low- (sensitivity 85%, specificity 79%) and 102 for the high- (sensitivity 85%, specificity 79%); in Crohn’s disease, 54 for the low- (sensitivity 71%, specificity 75%) and 122 for the high-range kit (sensitivity 71%, specificity 75%).

Conclusions

Fecal calprotectin concentration has good diagnostic accuracy for the detection of endoscopic activity in inflammatory bowel disease and performs better in ulcerative colitis than in Crohn’s disease.

Introduction

Inflammatory bowel disease (IBD) is a chronic disorder characterized by inflammatory activity in the digestive tract. It comprises two conditions, ulcerative colitis (UC) and Crohn’s disease (CD). IBD often presents an intermittent course, with alternating periods of activity in the form of flares, which are usually unpredictable, and periods of remission.

The activity of IBD is generally assessed using a combination of endoscopic, clinical, and analytical findings [[1], [2]]. However, there is often little correlation between these parameters [3]. First, endoscopy is the gold standard for the detection and quantification of intestinal inflammation and correlates with the severity and prognosis of the disease [[4], [5]]. Nevertheless, repeating colonoscopy is not feasible owing to the costs and potential adverse effects. Second, clinical indices frequently do not correlate with endoscopic indices or real inflammatory activity [[6], [7]]. Serum markers such as the erythrocyte sedimentation rate, C-reactive protein (CRP), and orosomucoid are not specific, because values can be high in extra-digestive inflammatory processes and the sensitivity is also low, particularly in infectious, autoimmune, or rheumatic diseases [[8], [9]]. Finally, fecal markers such as calprotectin and lactoferrin are more specific for digestive inflammation and more accurate than serological markers for evaluation of inflammatory activity in IBD [[10], [11], [12]].

Calprotectin is a 36-kDa glycoprotein with affinity for calcium and zinc belonging to the lipocalin family. It transports hydrophobic molecules and is found in the cytoplasm of inflammatory cells such as neutrophils (representing 60% of cytosolic proteins), activated monocytes, and macrophages [13]. Inflammation is followed by migration of these cells to the intestinal lumen. Therefore, the concentration of calprotectin in stool is directly proportional to the number of neutrophils in the intestinal lumen [[14], [15]]. The main advantage of calprotectin is that it is more specific and sensitive for detecting inflammation in the digestive mucosa than serological markers [[14], [16], [17]]. Furthermore, fecal calprotectin quantifies inflammation of the intestinal mucosa at an early stage, before serological markers can be detected [[17], [18]].

In recent years, fecal calprotectin has been shown to play a key role in the diagnosis and monitoring of IBD. It helps to differentiate IBD from functional bowel disorders and predict response to treatment and relapse. It can also be used to monitor activity and is more accurate than other serum biomarkers [19]. One of the most promising and current applications is the accuracy of calprotectin for evaluating endoscopic lesions in IBD. Previous publications in this area have shown a good correlation between elevated levels of calprotectin and endoscopic and histological lesions in IBD, and application of this biomarker is cheaper, easier, and safer than endoscopy [[1], [19], [20], [21], [22]].

The application of fecal calprotectin as a biomarker is open to debate. First, there is no set cut-off point for defining the normal fecal concentration or predicting inflammatory activity. Most studies of the usefulness of calprotectin are based on a small number of patients and are highly heterogeneous and endoscopic activity is not always taken as a reference in the assessment of intestinal inflammation. Similarly, the specificity and sensitivity of calprotectin differ between UC and CD and between different locations.

In this study, our primary objective was to analyze the ability of fecal calprotectin to predict the presence of endoscopic activity in IBD. As secondary objectives, we aimed to evaluate the accuracy of fecal calprotectin according to the location of endoscopic activity, the reliability of calprotectin for predicting endoscopic activity according to phenotype in CD, and the severity of endoscopic activity. We calculated the diagnostic accuracy of the cut-off points of other serum biomarkers and calprotectin and assessed the correlation between low- and high-range calprotectin.

Section snippets

Methods

We performed a prospective observational study of patients with IBD (UC and CD) who underwent clinically indicated colonoscopy. The patients were included consecutively from the IBD unit of Hospital Universitario de La Princesa, Madrid, Spain. The inclusion criteria were age ≥18 years, diagnosis of IBD (UC or CD), and clinical indication for colonoscopy (suspected clinically active disease, assessment of endoscopic activity after medical treatment, dysplasia surveillance for long-standing

Characteristics of the patients enrolled in the study

One-hundred patients diagnosed with IBD were included. The mean age was 47 years, and there were 52 women (52%) and 48 men (48%). A total of 48 patients (48%) had UC and 52 (52%) had CD. Of the total number of patients, 47 (47%) were receiving salicylates, 20 (20%) azathioprine, 15 (15%) adalimumab, eight (8%) corticosteroids, five (5%) mercaptopurine, five (5%) infliximab, four (4%) metrotexate, two (2%) ustekinumab, one (1%) certolizumab and six (6%) were receiving no treatment for IBD. Table

Discussion

The results of this study demonstrate that fecal calprotectin is a highly accurate predictor of endoscopic activity in IBD and that it is more accurate in UC than in CD. Calprotectin has already been studied as an indirect marker of inflammation and is useful for differentiating between organic and functional disease of the digestive tract and for predicting relapse and postoperative recurrence of IBD [[1], [21], [26], [27], [28]]. However, the correlation between fecal calprotectin and

Conflict of interest

Dr. Jusue declares no conflict or interest.

Dr. Gisbert has served as a speaker, a consultant and advisory member for or has received research funding from MSD, Abbvie, Hospira, Pfizer, Kern Pharma, Biogen, Takeda, Janssen, Roche, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, and Vifor Pharma.

Dr. Chaparro has served as a speaker, or has received research or education funding from MSD, Abbvie, Hospira,

References (47)

  • A. Poullis et al.

    Review article: faecal markers in the assessment of activity in inflammatory bowel disease

    Aliment Pharmacol Ther

    (2002)
  • J.E. Baars et al.

    Majority of patients with inflammatory bowel disease in clinical remission have mucosal inflammation

    Inflamm Bowel Dis

    (2012)
  • A.M. Schoepfer et al.

    Fecal calprotectin correlates more closely with the Simple Endoscopic Score for Crohn’s disease (SES-CD) than CRP, blood leukocytes, and the CDAI

    Am J Gastroenterol

    (2010)
  • J.P. Gisbert et al.

    Role of biological markers in inflammatory bowel disease

    Gastroenterol Hepatol

    (2007)
  • E. Burri et al.

    Monitoring of therapy for inflammatory bowel disease

    Digestion

    (2012)
  • A.G. Roseth et al.

    Assessment of the neutrophil dominating protein calprotectin in feces: a methodologic study

    Scand J Gastroenterol

    (1992)
  • P.F. van Rheenen et al.

    Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis

    BMJ

    (2010)
  • J.M. Benitez et al.

    Faecal calprotectin: management in inflammatory bowel disease

    World J Gastrointest Pathophysiol

    (2015)
  • M.K. Fagerhol et al.

    Calprotectin (The L1 leukocyte protein)

  • S. Vermeire et al.

    Laboratory markers in IBD: useful, magic, or unnecessary toys

    Gut

    (2006)
  • S. Vermeire et al.

    C-reactive protein as a marker for inflammatory bowel disease

    Inflamm Bowel Dis

    (2004)
  • J.A. Tibble et al.

    High prevalence of NSAID enteropathy as shown by a simple faecal test

    Gut

    (1999)
  • U. Kopylov et al.

    Clinical utility of fecal biomarkers for the diagnosis and management of inflammatory bowel disease

    Inflamm Bowel Dis

    (2014)
  • Cited by (0)

    View full text