A Nomogram Combining Fecal Calprotectin Levels and Plasma Cytokine Profiles for Individual Prediction of Postoperative Crohn’s Disease Recurrence

Abstract

Background The aims of this study were to characterize the immune response profile in patients with Crohn’s disease (CD) and early postoperative recurrence (POR), to identify predictive biomarkers, and to develop a noninvasive predictive tool for individual estimation of POR risk. Methods Sixty-one patients who had undergone ileocolonic resection for CD were prospectively included and followed up for 24 months. Fecal calprotectin (FC), analytical parameters, and plasma cytokines were obtained before surgery and at various time points during postoperative follow-up. Morphological recurrence was assessed by ileocolonoscopy or magnetic resonance enterography within 6–12 months after surgery. Clinical activity was scored using the Harvey-Bradshaw Index. Results Twenty-seven patients (44.3%) had morphological recurrence during follow-up. Fecal calprotectin values were significantly associated with POR risk over time. The receiver operating characteristic curve for FC provided an area under the curve (AUC) of 0.88 (95% confidence interval, 0.75–0.96), and morphological recurrence was best predicted by FC ≥160 μg/g at 6 months after surgery (85% sensitivity, 70% specificity, 26% predictive positive value, 98% negative predictive value [NPV]). The plasma cytokine profile showed higher presurgery interleukin (IL)-13 plasma levels and higher IL-6 and interferon (IFN)-γ levels at 6 months after surgery in patients with POR compared with patients without recurrence. The combination of FC, IL-6, and IFN-γ values at 6 months gave an AUC of 0.90 for predicting an early recurrence. Conclusions FC values <160 μg/g at 6 months have a high NPV to rule out early lesions. Combined values of FC, IL-6, and IFN-γ levels at 6 months postsurgery constitute a prognostic index with a high predictive capacity to assess the risk of early POR.

Is fecal calprotectin an accurate marker in the management of Crohn's disease?

“…It must be underlined that five studies followed up patients for 18–24 months and provide an accurate interpretation of the long‐term association between FC and POR. Moreover, the quality of the studies is more uniform than in the other sections of this review.…”

“…Moreover, the quality of the studies is more uniform than in the other sections of this review. All but two studies 65,70 had a prospective design (Table S1), and in all cases but one, 61 the definition of POR was based on the Rutgeerts score, rendering conclusions more reliable despite the small sample size of most series (Table 6 [57][58][59][60][61][62][63][64][65][67][68][69][70][71][72][73] ).…”

Correlation between Serological Biomarkers and Disease Activity in Patients with Inflammatory Bowel Disease

“…Recent studies have confirmed fecal calprotectin is the best biomarker for evaluating disease activity in IBD patients [20,21]. However, it is limited in clinical practice owing to its cost and discommodious sample collecting and processing.…”

Specific Plasma MicroRNA Signatures in Predicting and Confirming Crohn's Disease Recurrence: Role and Pathogenic Implications

“…Morphological recurrence was assessed by ileocolonoscopy or MRE within 6–12 months after surgery. Endoscopic activity in the neoterminal ileum was graded according to the Rutgeerts score: i0, no lesions; i1, ≤5 aphthous lesions; i2a, lesions confined to the ileocolonic anastomosis; i2b, >5 aphthous lesions with normal mucosa between lesions; i3, diffuse aphthous ileitis with diffusely inflamed mucosa; and i4, diffuse inflammation with larger ulcers, nodules, and/or narrowing, as previously indicated ( 26 ). Recurrence was defined as a Rutgeerts score ≥ i2b ( 27 ).…”