Original article
Alimentary tract
Level of Fecal Calprotectin Correlates With Severity of Small Bowel Crohn’s Disease, Measured by Balloon-assisted Enteroscopy and Computed Tomography Enterography

https://doi.org/10.1016/j.cgh.2016.08.015Get rights and content

Background & Aims

Previous studies have not found a correlation between fecal level of calprotectin and small bowel Crohn’s disease (CD). However, these studies evaluated patients mainly by ileocolonoscopy, which views up to only the terminal ileum rather than entire small intestine. We investigated whether level of fecal calprotectin (FC) is a marker of active CD of the small bowel, identified by balloon-assisted enteroscopy and computed tomography enterography (CTE).

Methods

We performed a prospective study of 123 patients with CD (35 with ileitis, 72 with ileocolitis, and 16 with colitis) evaluated by balloon-assisted enteroscopy from May 2012 through July 2015 at Toho University Sakura Medical Centre in Japan. Patients with strictures detected by balloon-assisted enteroscopy were evaluated by CTE (n = 17). Fecal samples were collected from each patient, and levels of calprotectin were measured; patient demographic variables and medical history were also collected. We developed a CTE scoring system for disease severity that was based on bowel wall thickness, mural hyperenhancement, and engorged vasa recta. The association between level of FC and simple endoscopic index for CD score or CTE was evaluated by using Spearman rank correlation coefficient.

Results

Level of FC correlated with the simple endoscopic index for CD score (r = 0.6362, P < .0001), even in patients with only active disease of the small intestine (r = 0.6594, P = .0005). In the 17 patients with strictures that could not be passed with the enteroscope, CTE detected all lesions beyond the strictures as well as areas in the distal side of the strictures. Level of FC correlated with CTE score in these patients (r = 0.4018, P = .0011, n = 63). In receiver operating characteristic analyses, the FC cutoff value for mucosal healing was 215 μg/g; this cutoff value identified patients with healing with 82.8% sensitivity, 71.4% specificity, positive predictive value of 74.3%, negative predictive value of 80.6%, odds ratio of 12.0, and area under the receiver operating characteristic curve value of 0.81.

Conclusions

A combination of measurement of level of FC and CTE appears to be effective for monitoring CD activity in patients with small intestinal CD, including patients with strictures that cannot be passed by conventional endoscopy.

Section snippets

Patients

Between May 2012 and July 2015, patients with a diagnosis of CD19 were enrolled into this prospective study at the Centre for Gastroenterology, Toho University Sakura Medical Centre. Patients who had very severe CD or needed immediate surgery were not included. The eligible patients (n = 89) underwent a total of 123 endoscopic examinations by BAE. Thirty-four of the 89 patients repeated endoscopy at a 6-month interval. In 82 patients, 100 BAE and CTE sessions were undertaken. From 70 patients

Patients’ Demographic Variables

A total of 89 patients, average age 31.8 years, were eligible for inclusion (Table 1). At the first endoscopy, the average CDAI was 120, range 0–401, and the average CRP was 1.09 mg/dL, range 0.01–9.13 mg/dL. Only 11 of the 89 patients (12.4%) were female. The average disease duration was 108 months. Twenty-seven patients (30.3%) had small bowel CD, 50 (56.2%) had ileocolonic CD, and 12 (13.5%) had colonic CD. Some patients had undergone multiple surgeries, which is common in CD patients

Discussion

We found that in patients with small bowel CD, the level of FC was well-correlated with the CD activity when the latter was defined by both BAE and CTE. Neither the CDAI score nor serum CRP showed similar correlation with FC regardless of CD location. Furthermore, CTE could reach and evaluate CD lesions in the small intestine unreachable by endoscopy. A good correlation between FC and the CTE findings should mean that both FC and CTE may define endoscopic mucosal healing.

At present, CRP is

References (28)

  • R. Ilangovan et al.

    CT enterography: review of technique and practical tips

    Br J Radiol

    (2012)
  • T. Sipponen et al.

    Crohn’s disease activity assessed by fecal calprotectin and lactoferrin: correlation with Crohn’s disease activity index and endoscopic findings

    Inflamm Bowel Dis

    (2008)
  • B.R. Canani et al.

    Faecal calprotectin as reliable non-invasive marker to assess the severity of mucosal inflammation in children with inflammatory bowel disease

    Dig Liver Dis

    (2008)
  • J. Langhorst et al.

    Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN-elastase, CRP, and clinical indices

    Am J Gastroenterol

    (2008)
  • Cited by (48)

    • Updates in the diagnosis and management of small-bowel Crohn's disease

      2023, Best Practice and Research: Clinical Gastroenterology
    • Biomarkers of disease activity and other factors as predictors of adalimumab pharmacokinetics in inflammatory bowel disease

      2020, European Journal of Pharmaceutical Sciences
      Citation Excerpt :

      On the other hand, there is controversy regarding the influence of the location of CD on the accuracy of the FCP to predict endoscopic lesions. While in some studies the accuracy is similar in different locations (Arai et al., 2016; Jensen et al., 2011), in most cases the correlation between FCP and endoscopic activity is lower in ileal disease than in colic or ileocolic (Lobatón et al., 2013; Stawczyk-Eder et al., 2015). Some authors have questioned the validity of these findings since the exploration of the ileum was performed by ileocolonoscopy and was considered incomplete since visualizing proximal small intestine sections was not possible (Guardiola et al., 2018).

    • Should We Divide Crohn's Disease Into Ileum-Dominant and Isolated Colonic Diseases?

      2019, Clinical Gastroenterology and Hepatology
      Citation Excerpt :

      This discrepancy across cohorts when using capsule endoscopy as a gold standard may be a result of variation in correlation between FC and different small-bowel capsule endoscopic disease activity indices.72 When using cross-sectional imaging as a gold standard for disease activity, some studies have suggested an optimal cut-off value of approximately 150 ug/g for defining active ileal CD,73 whereas others have suggested a cut-off value of approximately 200 ug/g when using balloon-assisted enteroscopy with or without cross-sectional imaging as the gold standard.74,75 Thus, FC may correlate with ileal CD activity, but the optimal cut-off value has yet to be determined and is influenced significantly by the diagnostic tool and scoring index used as the gold standard.

    View all citing articles on Scopus

    Conflicts of interest The authors disclose no conflicts.

    View full text