PTU-012 Faecal Calprotectin as Predictor of Small-Bowel Crohn’s Disease in Capsule Endoscopy – A Systematic Review and Meta-Analysis

Abstract

IntroductionFaecal calprotectin (FC) is a well-established marker of gut inflammation. While the correlation of elevated FC levels with colonic inflammation has been confirmed in several studies,1,2 data regarding the correlation of FC with small-bowel inflammation is either scarce or conflicting.3 Capsule endoscopy (CE) is the modality of choice for detection of small-bowel inflammation and/or small-bowel Crohn’s disease (CD).4 Therefore, we aimed to systematically review and meta-analyse the evidence for the diagnostic accuracy of FC as a predictor of small-bowel CD.MethodsA comprehensive literature search of the databases PubMed and Embase was performed, using the search string: “capsule endoscopy” + calprotectin. Studies including patients with suspected and/or established CD evaluated by both FC and CE were retrieved. Corresponding authors were contacted for any missing data. The following FC cut-offs were evaluated: >50, 100 and 200 μg/g, as available in each included study. A diagnostic meta-analysis was performed; pooled diagnostic sensitivity (Se), specificity (Sp) and diagnostic odds ratio (DOR) with 95% confidence intervals (95% CI) were obtained for each of the cut-offs. Bias was evaluated using the quality assessment of studies of diagnostic accuracy in systematic reviews (QUADAS) 2 tool. A minimum of 4 studies was required for each analysis.ResultsA total of 135 studies were identified; seven (3 prospective, 4 retrospective) studies, including 463 patients, entered the final analysis. Overall, the methodological quality of the studies was high, with 6/7 studies showing low risk of bias. For studies including only patients with suspected CD, the diagnostic accuracy of FC for the cut-off of 50 μg/g was as follows: 5 studies, 305 patients; Se 89% (CI 68%;97%), Sp 55% (CI 36%;73%), DOR 10.3 (CI 3.7;28.6) . For all included studies (suspected and established CD), the DOR was significant for all the evaluated FC cut-offs. FC > 50μg/g: 7 studies, 463 patients; Se 83% (CI 73%;90%), Sp 53% (CI 36%;71%), DOR 5.64 (CI 3.2;10.1). FC > 100μg/g: 5 studies, 379 patients; Se 68% (CI 56%;76%), Sp 71% (CI 46%;88%), DOR 5.01 (CI 2.03;12.07). FC > 200μg/g: 4 studies, 309 patients; Se 42% (CI 26%;64%), Sp 94% (CI 64%;99%), DOR 13.64 (CI 2.01;88.6). Sensitivity analysis based on methodological quality did not change those results significantly.ConclusionThis meta-analysis confirms that FC, when used as a predictor of small-bowel CD prior to CE, has high diagnostic accuracy. For patients with suspected CD, a FC cut-off level of 50 μg/g provided high sensitivity and DOR, while for the entire patient cohort (suspected and established CD) FC > 200 μg/g provided the best overall DOR. The likelihood of diagnosing small-bowel CD is extremely low in suspected CD patients with FC < 50μg/g.References1 D’Haens G, et al. Faecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 2012;18:2218–2224.2 Van Rheenen PF, et al. Faecal calprotectin for screening of patients with suspecte...

Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2022

“…Recent meta-analyses have consistently demonstrated that fecal calprotectin has significant diagnostic accuracy for detecting SB CD 120 121 122 . The likelihood of a positive diagnosis is very low in patients with suspected CD with calprotectin < 50 μg/g.…”

The Fecal Microbiome in Quiescent Crohn’s Disease with Persistent Gastrointestinal Symptoms Show Enrichment of Oral Microbes But Depletion of Butyrate and Indole Producers

“…However, our results remained robust even when we restricted our analysis to patients with FCP <50 mcg/g, which has the lowest false negative rate in detecting inflammation in CD. 20 These results suggest that the microbiome changes described here are likely independent from inflammation. Secondly, while these results support an association between microbial changes and persistent symptoms in quiescent CD, we cannot make any firm conclusions on causation here.…”

“…We thus repeated our analyses, but only included quiescent CD patients with a FCP <50 mcg/g, which has the lowest false negative rate for active inflammation in CD. 20 Overall, our results were not changed by this lower threshold for FCP. Specifically, Shannon index was significantly decreased in qCD+symptoms compared with qCD-symptoms, IBS-D, and healthy controls…”

Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – August 2021 – AWMF-Registernummer: 021-004

“…Das Vorliegen intermittierend erhöhter CRP- oder Calprotectin-Werte oder eine Eisenmangelanämie stellen u. a. Warnsymptome dar und können die Entscheidungsfindung unterstützen 63 64 . In einer jüngeren Metaanalyse konnte gezeigt werden, dass bei einem fäkalen Calprotectin-Wert < 50 µg/g das Vorliegen eines Dünndarmbefalls bei M. Crohn sehr unwahrscheinlich ist 65 . Wird eine Videokapselendoskopie bei V. a. M. Crohn durchgeführt, kann eine Patency-Kapsel zum Ausschluss einer relevanten Stenosierung vor Applikation der Videokapsel sinnvoll sein 62 66 , da bei bestehendem M. Crohn Kapsel-Retentionsraten in Metaanalysen mit bis zu 2–3 % angegeben werden 67 .…”