Fecal surrogate markers strongly correlate with endoscopic findings in pediatric onset inflammatory bowel disease: a retrospective study in Japan.

P-039: Assessing phenotype and disease prognosis in early onset IBD. Retrospective data from 2 tertiary centres in the United Kingdom and Italy

Use of fecal lactoferrin to diagnose irritable pouch syndrome: A word of caution

Inflammatory Bowel Disease Clinical

Faecal biomarkers are increasingly utilized for disease assessment in inflammatory bowel disease (IBD). To characterize the relative and combined accuracy of faecal calprotectin (FC) and faecal immunochemical testing (FIT) for detecting endoscopic and histologically active disease in Crohn's disease (CD) and ulcerative colitis (UC), subdivided by disease location. A prospective cohort study. Patients with confirmed IBD undergoing routine ileocolonoscopy for activity assessment were prospectively recruited and performed both FC and FIT ±30 days of ileocolonoscopy. Endoscopic activity was assessed via the simplified endoscopic score for CD, Mayo endoscopic score for UC and histological activity graded as nil/mild/moderate. Receiver-operator curve analyses were utilized to assess the performance of FC and FIT per disease subtype and location. In all, 137 (79 CD, 57 UC) patients were recruited. FC was more sensitive than FIT in detecting active endoscopic (CD: 91% versus 69%, UC: 94% versus 82%) and histological (CD: 86% versus 55%, UC 88% versus 56%) disease. However, FIT was more specific than FC in detecting active endoscopic (CD: 94% versus 56%, UC: 85% versus 69%) and histological (CD: 93% versus 55%, UC: 96% versus 70%) diseases. FIT was more sensitive and specific than FC in detecting active colonic CD (endoscopic activity: 94% versus 93%, histological activity: 92% versus 77%, respectively); however, it was poorly sensitive for active ileal CD (43% versus 89%). FC demonstrated higher sensitivity and FIT higher specificity for active IBD. Hence, dual testing was synergistic, displaying excellent performance characteristics across most IBD locations and subtypes, holding promise for future clinical application. Not applicable.

BACKGROUNDStudies have demonstrated a potential role for fecal biomarkers such as fecal calprotectin (FC) and fecal lactoferrin (FL) in monitoring inflammatory bowel diseases (IBD) - Crohn’s disease (CD) and ulcerative colitis (UC). However, their correlation to endoscopic scores, disease severity and affected intestinal surface has not been extensively investigated.AIMTo correlate FL, and for comparison white blood cell (WBC) and C-reactive protein (CRP), with endoscopic scores, disease extent and location in CD and UC.METHODSRetrospective analysis in 188 patients who had FL, CRP and WBC determined within 30 d of endoscopy. Disease location, disease extent (number of intestinal segments involved), disease severity (determined by endoscopic scores), timing of FL testing in relation to colonoscopy, as well as the use of effective fast acting medications (steroids and biologics) between colonoscopy and FL measurement, were recorded.RESULTSIn 131 CD and 57 UC patients, both CRP and FL - but not WBC - distinguished disease severity (inactive, mild, moderate, severe). In patients receiving fast-acting (steroids or biologics) treatment in between FL and colonoscopy, FL showed a higher correlation to endoscopic scores when tested before vs after the procedure (r = 0.596, P < 0.001, vs r = 0.285, P = 0.15 for the Simple Endoscopic Score for CD; and r = 0.402, P = 0.01 vs r = 0.054 P = 0.84 for Disease Activity Index). Finally, FL was significantly correlated with the diseased mucosal surface (colon-ileocolon > small bowel) and the number of inflamed colon segments.CONCLUSIONFL and CRP separated disease severity categories with FL showing lower discriminating P-values. FL showed a close correlation with the involved mucosal surface and with disease extent and was more closely correlated to endoscopy when determined before the procedure – this indicating that inflammatory activity changes associated with therapy might be rapidly reflected by FL levels. FL can accurately and timely characterize intestinal inflammation in IBD.

Background/Objectives: The prevalence of inflammatory bowel disease (IBD) in spondyloarthritis (SpA) patients is unknown. Our objective was to assess the prevalence of undiagnosed IBD in SpA patients, including those with axial spondylarthritis (axSpA) or psoriatic arthritis (PsA). Additionally, we examined fecal calprotectin (FC) levels in relation to the accuracy of IBD diagnosis. Methods: EISER was a cross-sectional, multicenter, observational, rheumatologist-gastroenterologist collaborative study. Patients with SpA naïve to biologics were recruited. Demographic and clinical characteristics, disease activity, and treatment information were collected. Patients with FC ≥ 80 µg/g or IBD-related symptoms underwent a colonoscopy or video capsule endoscopy. Receiver operating characteristic analysis assessed the predictive value of FC for IBD diagnosis. Results: Of the 570 patients recruited, 494 were evaluable for the main outcome, 248 (50.2%) had axSpA, and 246 (49.8%) had PsA. Overall, 28/494 patients were diagnosed with IBD (5.7%, 95%CI 3.6-7.7). Sorted by clinical entity, 22 (8.9%, 95%CI 5.3-12.4) axSpA and 6 (2.4%, 95%CI 0.5-4.4) PsA patients had a diagnosis of IBD: 24 (86%, 95%CI 79.4-92.6) had ileal/ileocolonic Crohn's disease (CD), 3 (11%, 95%CI 5.1-16.9) unclassified IBD, and 1 (3.5%, 95%CI 0.0-6.9) ulcerative colitis. The ROC curve for FC and IBD diagnosis (AUC: 0.870, p < 0.001, 95%CI 83.7-89.8) showed that an FC ≥ 147 µg/g had a positive predictive value of 17.4% (95%CI 14.5-20.8) Conclusions: In SpA, the prevalence of undiagnosed IBD was 5.7%, higher in axSpA (8.9%) than in PsA (2.4%) patients, with CD being the most common. SpA patients with FC levels < 147 µg/g had a very low probability of IBD.

Purpose: Fecal lactoferrin (FLA) is a neutrophil-derived surrogate marker of intestinal inflammation. Elevated FLA levels have been demonstrated in adult patients with inflammatory bowel disease (IBD). Aims: 1) Determine the ability of FLA to reflect disease activity in pediatric patients with inflammatory and non-inflammatory gastrointestinal disease. 2) Determine the correlation between FLA levels and existing biochemical markers of intestinal inflammation. Methods: Fecal specimens were collected from 148 subjects including 79 with Crohn's disease (CD), 62 with ulcerative colitis (UC), and 7 with Irritable Bowel Syndrome (IBS). FLA was measured by ELISA (IBD-SCAN™ TECHLAB®, Inc) and reported as mcg/ml feces. Disease activity was assessed using Harvey Bradshaw (HBAI) and Pediatric Crohn's Disease Activity Indices (PCDAI). Disease activity was also assessed by Global Physician Assessment (GPA), a derived dichotomous measure that characterizes disease activity based on whether or not a clinician felt a need to alter a subject's medical therapy. Results: Fecal lactoferrin levels were greater in subjects with IBD 1780 ± 326 vs. those with IBS 2.08 ± 0.9 (mean ± SE). The sensitivity and specificity of FLA to distinguish symptomatic subjects with IBD from those with IBS was 95% and 100%, respectively. FLA faithfully discriminated subjects with active IBD, CD, or UC from those with inactive disease (p <0.002) using HBAI, PCDAI, or GPA. Using a Spearman linear regression model, we found highly significant correlations (p <0.0001) between FLA and several commonly used biochemical indices including ESR, hema-tocrit, albumin, and platelet count. ROC analysis demonstrated that FLA outperformed ESR in distinguishing active vs. inactive IBD, UC and CD, but reached statistical significance only in subjects with UC (p = 0.016). FLA levels were significantly higher (1003 ± 547) in 4 subjects that went on to experience a clinical flare in their IBD within two months of specimen collection, relative to 51 subjects that remained in clinical remission (190 ± 90, p = 0.024). Conclusions: Our data confirm FLA as a useful screening tool for detecting IBD in pediatric patients. This non-invasive surrogate marker reflects intestinal disease activity with greater precision than ESR. Elevated levels of FLA may predict patients at greater risk for developing subsequent clinical flares.

BackgroundResearch has shown that fecal biomarkers are useful to assess the activity of inflammatory bowel disease (IBD). The aim of the study is: to evaluate the efficacy of the fecal lactoferrin and calprotectin as indicators of inflammatory activity.FindingsA total of 78 patients presenting inflammatory bowel disease were evaluated. Blood tests, the Crohn's Disease Activity Index (CDAI), Mayo Disease Activity Index (MDAI), and Crohn's Disease Endoscopic Index of Severity (CDEIS) were used for the clinical and endoscopic evaluation. Two tests were performed on the fecal samples, to check the levels of calprotectin and lactoferrin. The performance of these fecal markers for detection of inflammation with reference to endoscopic and histological inflammatory activity was assessed and calculated sensitivity, specificity, accuracy.A total of 52 patient's samples whose histological evaluations showed inflammation, 49 were lactoferrin-positive, and 40 were calprotectin-positive (p = 0.000). Lactoferrin and calprotectin findings correlated with C-reactive protein in both the CD and UC groups (p = 0.006; p = 0.000), with CDAI values (p = 0.043; 0.010), CDEIS values in DC cases (p = 0,000; 0.000), and with MDAI values in UC cases (p = 0.000).ConclusionFecal lactoferrin and calprotectin are highly sensitive and specific markers for detecting intestinal inflammation. Levels of fecal calprotectin have a proportional correlation to the degree of inflammation of the intestinal mucosa.

Background. Optimal management of pediatric patients with inflammatory bowel disease (IBD) requires early diagnosis. Aim of the study is to compare fecal lactoferrin (FL) as biomarker of intestinal inflammation to CRP in pediatric patients with new-onset IBD. Methods. FL was measured by ELISA in stool specimens collected prior to endoscopy for IBD (IBD-SCAN; TechLab, Blacksburg; normal < 7.3 µg/g feces). CRP was detected in serum (normal < 5 mg/L). Three patient groups were determined: n = 21 (mean age 13.2) with Crohn's disease (CD), n = 15 (mean age 10.9) with ulcerative colitis (UC), and n = 20 (mean age 11.9) in whom IBD was ruled out. In CD patients the endoscopic severity score SES-CD was correlated with the FL levels. Results. (Mean ± SEM). CRP levels were 27.18 ± 4.2 for CD-cases, 20.8 ± 9.5 for UC, and 0.24 ± 0.06 for non-IBD patients. FL levels were 313.6 ± 46.4 in CD, 370.7 ± 46.9 in UC, and 1.3 ± 0.5 in non-IBD patients. Sensitivity of CRP to detect IBD was 75% with specificity of 100%, positive predictive value of 100%, and negative predictive value of 69%. Sensitivity of FL was 100% with specificity of 95%, positive predictive value of 97.3%, and negative predictive value of 100%. In CD, FL levels correlated positively (R2 = 0.42) with disease severity as judged by the SES-CD. Conclusions. Elevated FL corresponds to intestinal inflammation, even in patients with normal CRP. With high probability, normal FL excludes intestinal inflammation.

P-049: Reproducibility of serologic antibody activity at diagnosis and after treatment in pediatric ulcerative colitis and Crohn’s disease

The usefulness of second-generation colon capsule endoscopy (CCE2) in ulcerative colitis (UC), especially in clinically inactive patients, has been reported. Capsule Scoring of Ulcerative Colitis (CSUC) was developed as a severity index for UC. We aimed to determine whether CSUC is useful for predicting relapse during clinical remission. Forty-one UC patients in clinical remission who underwent CCE2 were prospectively registered from April 2016 to August 2019. Patients' CSUC score was obtained; those with subsequent relapse were followed up retrospectively. The correlation of CSUC with white blood cell count, platelet count, albumin, C-reactive protein, fecal calprotectin and fecal lactoferrin levels, and fecal immunochemical test results was evaluated; their predictive values for future relapse were compared. The correlations of CSUC with white blood cell, platelet, albumin, C-reactive protein, fecal calprotectin, fecal immunochemical test, and fecal lactoferrin values were rs =0.13, 0.27, -0.25, 0.15, 0.50, 0.43, and 0.50, respectively. CSUC was higher in 12 patients who relapsed within 1year than in 29 patients who remained in clinical remission (2.83±1.95 vs 0.72±1.00, P<0.01). Receiver operator characteristic curve analysis showed that CSUC ≥1 was a predictor of relapse (area under the curve of 0.82, sensitivity of 83.3%, specificity of 58.6%) and maybe superior to fecal biomarkers. In the univariate analysis, patients with CSUC of 0 had a lower relapse rate than those with CSUC of ≧1 (P=0.03, log-rank test). After analyzing patients who underwent CCE2 within 6months after the successful induction treatment, results showed that those with CSUC of ≤1 remained in clinical remission for a year. CSUC predicts relapse within 1year in UC patients in clinical remission, especially when used 6months after induction treatment.

Pediatric inflammatory bowel disease (PIBD) has traditionally been prevalent in Western regions, but its incidence is rising globally, particularly in pediatric cases. Our study, conducted in Sri Lanka, a developing...

P786 Correlation between the presence of Bacteroidetes and faecal calprotectin for the detection of endoscopic activity in patients with inflammatory bowel disease

Noninvasive biomarkers of intestinal inflammation can reduce the number of endoscopies in children with inflammatory bowel disease (IBD). This study aimed to prospectively investigate the usefulness of fecal calprotectin (FCP) and fecal immunochemical test (FIT) in pediatric IBD. Patients aged 6-17years who underwent ileocolonoscopy for established or suspected IBD were eligible for this study. Fecal samples for FCP and FIT were collected before colonoscopy. A total of 251 samples were analyzed: 88 from ulcerative colitis (UC), 74 from Crohn's disease (CD), 75 from healthy controls (HC), and 14 from children with functional gastrointestinal disorders and normal colonoscopy (NC). At IBD diagnosis, both FCP and FIT were significantly higher in the newly diagnosed UC/CD group than in the HC/NC group (P < 0.001). The optimal cutoffs of FCP and FIT to predict IBD diagnosis were 217mg/kg and 87ng/mL, respectively. Patients without mucosal healing (MH) showed higher FCP and FIT than those with MH in both UC and CD (P < 0.001). The FCP increased exponentially as the endoscopic activity score increased. The optimal cutoff values of FCP and FIT for predicting MH were 161mg/kg and 106ng/mL for UC and 367mg/kg and 57ng/mL for CD, respectively. FCP showed better specificity than the FIT. Patients with CD and normal ileocolonoscopy had elevated FCP during active small intestinal inflammation. Both FCP and FIT correlate well with endoscopic activity in pediatric patients with IBD. The FCP is a superior marker for predicting MH.

Introduction: The incidence of early-onset inflammatory bowel disease is increasing in Japan. Objective: This study aimed to analyze the treatment and progress of early-onset inflammatory bowel disease. Methods: This prospective survey evaluated the data of 43 patients aged <8 years who were diagnosed with inflammatory bowel disease (IBD) from the time of diagnosis to 36 months after registration. Results: A total of 12 patients with Crohn’s disease (CD), 21 with ulcerative colitis (UC), and 3 with unclassified IBD were enrolled. The mean disease onset age was 3 years and 7 months. Colon and anal lesions were present in 100 and 50% of patients with CD, respectively. Granulomas were detected in 5 patients (41.7%). Dietary elimination including elemental diet was performed in all patients. Eleven patients (91.7%) were in remission by initial induction therapy, and 72.7% maintained remission for 36 months. Three patients (14.3%) with UC had familial history, 71.4% had pancolitis-type UC, and 66.7% exhibited disease of moderate severity. Colectomy was performed in 4 patients (21.1%). Eighteen patients (85.7%) were in remission by initial induction therapy; however, only 15.8% maintained remission for 36 months. Anal complication was more prevalent in infantile-onset IBD than in childhood-onset IBD (p = 0.014). Conclusions: Among Japanese patients aged <8 years who were diagnosed with IBD, colitis-type disease was more common in CD and pancolitis was more common in UC. As the courses of several patients were severe, identifying primary immunodeficiency appears to be necessary to confirm background disease.