Alimentary TractAccuracy of fecal calprotectin for the prediction of endoscopic activity in patients with inflammatory bowel 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,
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