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

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 mu g/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)-gamma levels at 6 months after surgery in patients with POR compared with patients without recurrence. The combination of FC, IL-6, and IFN-gamma values at 6 months gave an AUC of 0.90 for predicting an early recurrence. Conclusions: FC values <160 mu g/g at 6 months have a high NPV to rule out early lesions. Combined values of FC, IL-6, and IFN-gamma levels at 6 months postsurgery constitute a prognostic index with a high predictive capacity to assess the risk of early POR.