Noninvasive Fecal Immunochemical Testing and Fecal Calprotectin Predict Mucosal Healing in Inflammatory Bowel Disease

Objective: Fecal calprotectin (FC) is a promising marker for assessment of inflammatory bowel disease (IBD) activity. However, the utility of FC for predicting mucosal healing (MH) of IBD patients has yet to be clearly demonstrated. The objective of our study was to perform a meta-analysis evaluating the diagnostic accuracy of FC in predicting MH of IBD patients. Methods: We systematically searched the databases for studies from inception to April 2020 that evaluated MH in IBD. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. The extracted data were pooled using a summary receiver operating characteristic curve model. Random-effects model was used to summarize the diagnostic odds ratio, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. Results: Sixteen studies comprising 1,682 ulcerative colitis (UC) patients and 4 studies comprising 221 Crohn’s disease (CD) patients were included. The best performance of FC for predicting MH in UC was at cut-off range of 60–75 μg/g with area under the curve (AUC) of 0.88 and pooled sensitivity and specificity of 0.87 and 0.79, respectively. The pooled sensitivity and specificity values of cutoff range 180–250 μg/g for predicting MH in CD were 0.67 and 0.76, respectively. The AUC of 0.79 also revealed improved discrimination for identifying MH in CD with FC concentration. Conclusion: Our meta-analysis has found that FC is a simple, reliable noninvasive marker for predicting MH in IBD patients. FC cutoff range 60–75 μg/g appears to have the best overall accuracy in UC patients.

Download Full-text

Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease

Scientific Reports ◽

10.1038/s41598-021-90441-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eriko Yasutomi ◽

Toshihiro Inokuchi ◽

Sakiko Hiraoka ◽

Kensuke Takei ◽

Shoko Igawa ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Fecal Calprotectin ◽

Mucosal Healing ◽

C Reactive Protein ◽

Reactive Protein ◽

Immunochemical Test ◽

Fecal Markers ◽

Inflammatory Bowel

AbstractLeucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn’s disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.

Download Full-text

P110 ASSOCIATION OF FECAL CALPROTECTIN WITH ENDOSCOPIC AND HISTOLOGY ACTIVITY IN PEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.038 ◽

2020 ◽

Vol 26 (Supplement_1) ◽

pp. S16-S16

Author(s):

Erin Crawford ◽

Catherine Gestrich ◽

Sindhoosha Malay ◽

Thomas Sferra ◽

Shahrazad Saab ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Disease Severity ◽

Bowel Disease ◽

Severe Disease ◽

Fecal Calprotectin ◽

Mucosal Healing ◽

Control Population ◽

Moderate Disease ◽

Endoscopic Remission ◽

Inflammatory Bowel

Abstract Background Inflammatory bowel disease (IBD) treatment strategies have evolved to target mucosal healing, which has been shown to be associated with clinical remission and reduced complications. Fecal calprotectin (FC) is a non-invasive marker of intestinal inflammation, and has been shown to correlate with disease activity in IBD patients, though values which correlate with mucosal healing vary across studies. We aim to examine the association of quantitative FC levels with endoscopic and histologic severity, and compare FC in IBD patients with endoscopic remission with a control population. Methods We conducted a retrospective chart review of patients who had a FC completed between 30 and 1 days before colonoscopy at UH Rainbow Babies and Children’s Hospital between 2014 and 2018. IBD patients had disease severity endoscopically graded using the SES-CD or Mayo UC score, and had disease severity histologically graded using the Geboes method. Severity was classed as no disease, mild, moderate or severe. FC values of IBD patients with mucosal healing and the control population (those without gastrointestinal pathology or diagnosis on evaluation) were compared. Results 331 cases were included in the study; 107 IBD cases and 224 controls. 63 patients (19%) had a diagnosis of Crohn’s disease (CD) and 44 patients (13%) had ulcerative colitis (UC). When assessing endoscopic scoring of IBD patients, the median FC was lowest in those with no disease (181 ug/g), followed by those with mild and moderate disease (499, 599 ug/g) and highest in those with severe disease (921 ug/g). There was significance comparing no disease to moderate and severe disease (p=0.019, 0.003), and between mild and severe disease (p=0.012). When assessing histology, the median FC was lowest in IBD patients with no disease (328 ug/g), followed by those with mild and moderate disease (399 ug/g, 674 ug/g) and highest in those with severe disease (895 ug/g). There was significance comparing no disease to moderate and severe disease (p=0.021, 0.018). In CD patients, there was significance in FC between no disease and moderate and severe disease (p=0.047, 0.0047) on endoscopic scoring. In UC patients, there was significance in FC between no disease and moderate disease (p=0.023) for histologic scoring. When comparing FC of endoscopically normal patients, the control group had a significantly lower median FC than the IBD population with endoscopic remission (43 ug/g vs 181 ug/g, p=0.018). Conclusion FC showed association with disease severity on gross endoscopy and histology and significance between severities in our IBD cohort. Additionally, normal cut-off values of FC may depend on the presence or absence of underlying disease. While larger studies are needed, this noninvasive test may help mitigate frequency of invasive procedures.

Download Full-text

Biochemical Biomarkers of Mucosal Healing for Inflammatory Bowel Disease in Adults

Diagnostics ◽

10.3390/diagnostics10060367 ◽

2020 ◽

Vol 10 (6) ◽

pp. 367 ◽

Cited By ~ 2

Author(s):

Małgorzata Krzystek-Korpacka ◽

Radosław Kempiński ◽

Mariusz Bromke ◽

Katarzyna Neubauer

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Fecal Calprotectin ◽

Mucosal Healing ◽

Serum Marker ◽

Lipocalin 2 ◽

Comprehensive Overview ◽

Reactive Protein ◽

Golden Standard ◽

Inflammatory Bowel

Mucosal healing (MH) is the key therapeutic target of inflammatory bowel disease (IBD). The evaluation of MH remains challenging, with endoscopy being the golden standard. We performed a comprehensive overview of the performance of fecal-, serum-, and urine-based biochemical markers in colonic IBD to find out whether we are ready to replace endoscopy with a non-invasive but equally accurate instrument. A Pubmed, Web of Knowledge, and Scopus search of original articles as potential MH markers in adults, published between January 2009 and March 2020, was conducted. Finally, 84 eligible studies were identified. The most frequently studied fecal marker was calprotectin (44 studies), with areas under the curves (AUCs) ranging from 0.70 to 0.99 in ulcerative colitis (UC) and from 0.70 to 0.94 in Crohn`s disease (CD), followed by lactoferrin (4 studies), matrix metalloproteinase-9 (3 studies), and lipocalin-2 (3 studies). The most frequently studied serum marker was C-reactive protein (30 studies), with AUCs ranging from 0.60 to 0.96 in UC and from 0.64 to 0.93 in CD. Fecal calprotectin is an accurate MH marker in IBD in adults; however, it cannot replace endoscopy and the application of calprotectin is hampered by the lack of standardization concerning the cut-off value. Other markers are either not sufficiently accurate or have not been studied extensively enough.

Download Full-text

Fecal calprotectin measurement is a marker of short-term clinical outcome and presence of mucosal healing in patients with inflammatory bowel disease

World Journal of Gastroenterology ◽

10.3748/wjg.v23.i41.7387 ◽

2017 ◽

Vol 23 (41) ◽

pp. 7387-7396 ◽

Cited By ~ 25

Author(s):

Athanasios Kostas ◽

Spyros I Siakavellas ◽

Charalambos Kosmidis ◽

Anna Takou ◽

Joanna Nikou ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Clinical Outcome ◽

Bowel Disease ◽

Fecal Calprotectin ◽

Mucosal Healing ◽

Short Term ◽

Inflammatory Bowel

Download Full-text

Home monitoring of disease activity and fecal calprotectin in adult patients with inflammatory bowel disease – interim analysis of 68 patients

10.26226/morressier.59a6b343d462b80290b5443a ◽

2017 ◽

Author(s):

Dorit Ankersen

Keyword(s):

Inflammatory Bowel Disease ◽

Disease Activity ◽

Bowel Disease ◽

Interim Analysis ◽

Home Monitoring ◽

Fecal Calprotectin ◽

Adult Patients ◽

Inflammatory Bowel

Download Full-text

Predicting disease course in ulcerative colitis using stool proteins identified through an aptamer-based screen

Nature Communications ◽

10.1038/s41467-021-24235-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Sanam Soomro ◽

Suresh Venkateswaran ◽

Kamala Vanarsa ◽

Marwa Kharboutli ◽

Malavika Nidhi ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Fecal Calprotectin ◽

Disease Monitoring ◽

Disease Course ◽

Lipocalin 2 ◽

Time Points ◽

Inflammatory Bowel ◽

Stool Samples

AbstractIn the search for improved stool biomarkers for inflammatory bowel disease (IBD), an aptamer-based screen of 1129 stool proteins was conducted using stool samples from an IBD cohort. Here we report that of the 20 proteins subsequently validated by ELISA, stool Ferritin, Fibrinogen, Haptoglobin, Hemoglobin, Lipocalin-2, MMP-12, MMP-9, Myeloperoxidase, PGRP-S, Properdin, Resistin, Serpin A4, and TIMP-1 are significantly elevated in both ulcerative colitis (UC) and Crohn’s disease (CD) compared to controls. When tested in a longitudinal cohort of 50 UC patients at 4 time-points, fecal Fibrinogen, MMP-8, PGRP-S, and TIMP-2 show the strongest positive correlation with concurrent PUCAI and PGA scores and are superior to fecal calprotectin. Unlike fecal calprotectin, baseline stool Fibrinogen, MMP-12, PGRP-S, TIMP-1, and TIMP-2 can predict clinical remission at Week-4. Here we show that stool proteins identified using the comprehensive aptamer-based screen are superior to fecal calprotectin alone in disease monitoring and prediction in IBD.

Download Full-text

Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study

Journal of Gastroenterology ◽

10.1007/s00535-021-01793-0 ◽

2021 ◽

Author(s):

Shinichiro Shinzaki ◽

Katsuyoshi Matsuoka ◽

Hiroki Tanaka ◽

Fuminao Takeshima ◽

Shingo Kato ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Fecal Calprotectin ◽

Potential Biomarker ◽

Adalimumab Therapy ◽

Adalimumab Treatment ◽

Inflammatory Bowel

Abstract Background This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD). Methods Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn’s disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC. Results A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426). Conclusions Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

Download Full-text

AB0702 THE FREQUENCY OF INFLAMMATORY BOWEL DISEASES IN PATIENTS WITH ANKYLOSING SPONDYLITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3798 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1647.2-1647

Author(s):

G. Lukina ◽

P. Kulakova ◽

N. Savenkova ◽

E. Volnukhin ◽

A. Kovshik ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Longitudinal Study ◽

Ankylosing Spondylitis ◽

Disease Activity ◽

Bowel Disease ◽

Rapid Test ◽

Neutrophil Infiltration ◽

Fecal Calprotectin ◽

High Disease Activity ◽

Inflammatory Bowel

Background:Аnkylosing Spondylitis (AS) is closely associated with inflammatory bowel disease (IBD). About 6-46% of patients with IBD have various lesions of the musculoskeletal system [1]. 5-10% of patients with spondylarthritis (SpA) eventually develop IBD, with Crohn’s disease (CD) being more common than Ulcerative colitis (UC) [2]. Determining the level of fecal calprotectin (FC) is a study that allows to diagnose IBD. The concentration of FC directly depends on the neutrophil infiltration of the intestinal mucosa and has a direct connection with the activity of the inflammatory process [3]. It is known that level of FC increases in 2/3 of patients with AS and is closely related to parameters reflecting higher disease activity [4].Objectives:The aim of this study was to evaluate the frequency of IBD in patients with AS using an assessment of FC level.Methods:In the analysis were included 40 patients with AS, fulfilling the modified New York criteria, among them man -26 (65%), woman -14 (35%), mean age of patients was 41.2 ±10.5, mean disease duration - 13±8.8 years. All patients were examined with ESR, CRP, esophagogastroduodenoscopy, colonoscopy and quantitative analysis of the fecal calprotectin levels using the method of lateral immunochromatography with the BUHLMANN Quantum Blue rapid test. Standart range: 100-1800 µg /g.Results:All patients had a high disease activity, mean BASDAI was 5.2 ± 1.7, mean ASDAS CRP 3.8 ± 1.1. 35 patients (87.5 %) had FC level more than 100 µg / g, the remaining 5 patients (12.5%) less than 100 µg /g. 12 patients (30 %) had FC level more than 1,800 µg / g, 23 (57.5 %) from 101 µg / g to 1800 µg / g. All patients with FC levels more than 100 µg / g showed an increase CRP (mean 28.4 mg / l) and ESR (mean 36.3 mm\h) levels. IBD were diagnosed in 9 cases (22.5%): 5 patients (12.5 %) with CD and 4 patients (10 %) - UC, in the remaining cases (77.5%) was no intestinal pathology.Conclusion:The results showed high frequency of IBD in patients with AS. Patients with high FC levels (more than 100 μg/g) had high disease activity (AS). In most cases, inflammatory bowel disease were diagnosed in patients with FC levels more than 100 µg/g.References:[1] Bernstein CN, Blanchard JF, Rawsthorne P, Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol. 2001 Apr;96(4):1116-22.[2] Klingberg, E., Strid, H., Stahl, A.et al. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. Arthritis Res Ther 2017. 19(1):21[3] Cypers H, Varkas G, Beeckman S, et al. Elevated calprotectin levels reveal bowel inflammation in spondyloarthritis. Annals of the Rheumatic Diseases. 2016. 75:1357-1362[4] Arzu Duran, Senol Kobak, Nazime Sen, et al. Fecal calprotectin is associated with disease activity in patients with ankylosing spondylitis. Bosnian Journal of Basic Medical Sciences. 2016. 16 (1):71-4Disclosure of Interests:Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Polina Kulakova: None declared, Nadezhda Savenkova: None declared, Evgeniy Volnukhin: None declared, Anton Kovshik: None declared, Elena Alexandrova: None declared, Alexandr Novikov: None declared

Download Full-text