Analysis of Endoscopic Evaluation Reliability for Ulcerative Colitis in Histological Remission

The Mayo endoscopic subscore (MES) is a major endoscopic scoring system used to assign a status of mucosal inflammation and disease activity to patients with ulcerative colitis (UC). Using interobserver reliability (IOR), this study clarified the difficulties for endoscopic observers imposed by MES parameters used for the endoscopic evaluation of UC in histological remission. First, 42 endoscopists of four observer groups examined each MES parameter, which were evaluated from endoscopically obtained images of 100 cases as Grade 0 or 1 of the Nancy histological index of histopathological inflammation. Then, IOR was assessed using multiple κ statistics for each finding of MES. The results showed that IOR among all the observers was slight or fair for all the parameters, indicating a low IOR. The experts of the UC practice group had “moderate” or higher IOR for seven of the nine parameters, whereas “slight” or “fair” results were found for all parameters by the trainee group. The IOR for each MES parameter was calculated separately for the observer groups. All the groups showed “slight” or “fair” for “Erythema” and “Decreased vascular pattern”. Large differences between the endoscopists were found in the IOR for the MES parameters in UC in histological remission. Even among UC practice experts, the IOR was low for “Erythema” and “Decreased vascular pattern”.

Download Full-text

OP09 Patient reported outcomes reflect histologic disease activity in patients with Ulcerative Colitis: Interim analysis of the APOLLO study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab075.008 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S008-S009

Author(s):

B Verstockt ◽

C Jorissen ◽

E Hoefkens ◽

N Lembrechts ◽

L Pouillon ◽

...

Keyword(s):

Ulcerative Colitis ◽

Disease Activity ◽

Patient Reported Outcomes ◽

Activity Index ◽

Remission Rate ◽

Stool Frequency ◽

Patient Reported ◽

Endoscopic Remission ◽

Histological Remission ◽

General Wellbeing

Abstract Background Treating beyond endoscopic remission, aiming for histological remission, has shown to reduce relapse and hospitalization rates in patients with ulcerative colitis (UC). However, very little is known on how histological remission associates with patient reported outcomes (PROMs). Methods PROMs (Simple clinical colitis activity index [SCCAI], IBD disk and Visual Analogue Scales [VAS]) were prospectively collected through a digital questionnaire in all patients with UC undergoing colonoscopy between July 21st 2020-Jan 21st 2021. Mayo endoscopic sub score and UCEIS were determined, as well as the Nancy histologic index (NHI) of the most affected area. Endoscopic remission was defined as Mayo endoscopic sub score 0 and UCEIS 0; histologic remission as NHI 0, absence of active inflammation as NHI ≤ 1. PRO2 remission was defined as stool frequency ≤ 1 (absolute stool frequency ≤ 3 OR 1–2 stools more than usual) and rectal bleeding score of 0. Results Fifty-six paired assessments were collected in 48 unique patients (Table 1), with a histologic, endoscopic and PRO-2 remission rate of 23.2%, 28.6% and 38.2% respectively. Patients with histologic remission or absence of histologic inflammation had a significantly lower overall IBD disability (p=0.007, p=0.003) and disease activity score (p=0.003, p<0.001), as compared to patients without. In line, NHI correlated with the overall IBD disk (r=0.40, p=0.002) and SCCAI score (r=0.50, p<0.001). Many individual components of both scores (abdominal pain, arthralgia, impact on education and work/interpersonal interactions/sexual function, regulation of defecation, blood loss, general wellbeing, joint pain, numbers of stools during night/day, urgency) differed significantly between patients with and without histologic remission. VAS scores assessing general wellbeing (r=0.33, p=0.01), impact on daily activities (r=0.41, p=0.002), UC-related symptoms (r=0.42, p=0.001) and worries (r=0.40, p=0.002) correlated with histology. Quartile analysis of the overall IBD disk and SCCAI scores confirmed the highest likelihood for histologic remission in patients with the lowest scores (Q1-Q2 vs Q3-Q4 39.3% vs 7.1%, p=0.01; 40.0% vs 9.7%, p=0.01) (Figure 1). Nevertheless, the overall accuracy of the IBD disk (0.75) or SCCAI score (0.76) for histologic remission is lower (p<0.05) than the accuracy of the Mayo endoscopic (0.90) or UCEIS (0.90) score. Table 1: Baseline features Abstract OP09 – Figure 1: Quartile analysis Conclusion In patients with UC, PROMs for disability and clinical disease activity reflect histologic disease activity and should therefore be further explored in (trial) endpoint discussions. However, they cannot fully replace endoscopic and histologic findings, and should be considered complementary.

Download Full-text

Obestatin/Ghrelin Ratio as a New Activity Index in Ulcerative Colitis

International Journal of Innovative Research in Medical Science ◽

10.23958/ijirms/vol04-i04/623 ◽

2019 ◽

Vol 4 (04) ◽

Author(s):

Mohammed Amin Mohammed ◽

Nesreen Moustafa Omar

Keyword(s):

Ulcerative Colitis ◽

Disease Activity ◽

Mrna Expression ◽

Activity Index ◽

Strong Relationship ◽

Serum Levels ◽

Ghrelin Level ◽

Mucosal Inflammation ◽

Predictive Values ◽

Serum Ghrelin

Background and Aim: Ulcerative colitis (UC) is an immune-mediated systemic inflammatory process that destroys the intestinal mucosa. Ghrelin, an appetite-regulatory hormone, has anti-inflammatory effects including a decrease in circulating cytokines. Some reports demonstrated a strong relationship between the serum ghrelin level and the severity of mucosal inflammation in the gastrointestinal tract. The aim is to investigate serum levels and colonic mucosal mRNA expression of ghrelin, obestatin, and obestatin/ghrelin ratio in patients with UC and to determine their potential as markers for UC disease activity. Patients and Methods: seventy-five outpatients with UC and 45 age- and sex-matched healthy volunteers were enrolled in this study after written conscious consent and approval by the Institutional Review Board of Mansoura University. UC was diagnosed by conventional clinical, radiological, endoscopic, and histopathological criteria. Serum ghrelin, obestatin levels, and their mucosal mRNA expression were measured by ELISA kits and a real-time quantitative reverse transcriptase polymerase chain reaction according to the manufacturer’s protocols. Results: Serum levels and mucosal mRNA expression of ghrelin were significantly higher in patients with active UC than patients in remission p˂0.0001). Obestatin/ghrelin ratio was significantly lower in patients with active UC (0.26±0.08) than those in remission (0.523±0.16; p˂0.0001). Obestatin/ghrelin ratio was negatively and significantly correlated with inflammation and endoscopic scores, colitis activity index, serum ghrelin level, and its mucosal mRNA expression (p˂0.05). Conclusion: obestatin/ghrelin ratio might be a reliable surrogate non-invasive marker of disease activity in UC with significantly high sensitivity, specificity, predictive values, and diagnostic accuracy.

Download Full-text

Probe-based confocal laser endomicroscopy for in vivo assessment of histological healing in ulcerative colitis: development and validation of the ENHANCE index

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa255 ◽

2020 ◽

Author(s):

Gabriel Rahmi ◽

Emmanuel Coron ◽

Guillaume Perrod ◽

Michael Levy ◽

Jacques Moreau ◽

...

Keyword(s):

Ulcerative Colitis ◽

Disease Activity ◽

Vessel Diameter ◽

Mucosal Inflammation ◽

Confocal Laser Endomicroscopy ◽

Confocal Laser ◽

Colorectal Mucosa ◽

Expert Pathologist ◽

Histological Data

Abstract Background and aims Histological healing may represent the ultimate therapeutic goal in ulcerative colitis (UC), but it requires biopsies. Our aim was to develop a non-invasive index able to assess histological disease activity in ulcerative colitis using probe based confocal laser endomicroscopy (pCLE). Methods One hundred patients with quiescent UC were prospectively included in 5 French centres. After fluorescein intravenous injection, during colonoscopy, the colorectal mucosa was analysed by white light imaging, pCLE and then biopsied in different locations. Five endoscopists performed central reading of pCLE images blindly to clinical, endoscopic and histological data. One expert pathologist performed a central histological reading (Nancy index: gold standard). An univariate and multivariate analysis were performed to identify the endomicroscopic items associated with the presence of histologically active disease. Results Over 1000 pCLE videos sequences performed in 100 UC patients in endoscopic remission (Mayo 0 and 1) were evaluated. We observed that vessel diameter > 20 µm, dilated crypt lumen, fluorescein leakage and irregular crypt architecture were statistically associated with histologically proven inflammation according to the Nancy index. Hence, we built a pCLE index of mucosal inflammation that overall accuracy was of 79.6% and overall sensitivity and specificity were respectively of 57.8% and 82.8%. Negative predictive value, especially when a pCLE index ≤ 1 is observed was high (93.1%). Conclusion Using a robust methodology, large vessel diameter, dilated crypt lumen, fluorescein leakage and irregular crypt architecture are reliable endomicroscopic items defining the ENHANCE index for real-time assessment of histological disease activity in UC.

Download Full-text

A Novel Capsule Endoscopic Score for Crohn’s Disease

Crohn's & Colitis 360 ◽

10.1093/crocol/otaa040 ◽

2020 ◽

Vol 2 (2) ◽

Author(s):

Teppei Omori ◽

Takayuki Matsumoto ◽

Toshifumi Hara ◽

Harutaka Kambayashi ◽

Shun Murasugi ◽

...

Keyword(s):

Crohn’S Disease ◽

Small Bowel ◽

Crohn's Disease ◽

Disease Activity ◽

Capsule Endoscopy ◽

Scoring System ◽

Activity Index ◽

Intraclass Correlation ◽

Mucosal Inflammation ◽

Crohn’S Disease Activity

Abstract Background and Aims The Lewis Score (LS) and Capsule Endoscopy Crohn’s Disease Activity Index (CECDAI) are the two currently used small bowel capsule endoscopy (SBCE) scoring systems for Crohn’s disease (CD). The present study describes a new scoring system for evaluation of small bowel CD, especially mucosal inflammation. Methods In this cross-sectional study, 108 CD patients underwent 196 SBCEs. The small bowel lesions were scored using our new Crohn’s Disease Activity in Capsule Endoscopy (CDACE). CDACE is the sum of scores for location of inflammation, range of inflammation, and stenosis, with a value ranging from 0 to 1643. We analyzed the relation between CDACE and LS, CECDAI, CDAI, and CRP values and evaluated the inter-rater reliability of CDACE using the intraclass correlation coefficient (ICC) (2.1). Results The mean (±SD) values of LS, CECDAI, and CDACE were 501 ± 1177, 5.8 ± 5.4 and 431 ± 356, respectively. CDACE correlated significantly with LS and CECDAI (ρ = 0.737, P < 0.0001 for LS and ρ = 0.915, P < 0.0001 for CECDAI). CDACE also correlated significantly with CDAI (ρ = 0.36) and CRP (ρ = 0.23). The ICC (2.1) was 0.829, indicating strong agreement among readers. Conclusions CDACE is a potentially useful SBCE scoring system for small bowel CD, as it represents the extent and spread of small bowel mucosal inflammation and stenosis.

Download Full-text

P146 Comparison of three histologic indices in ulcerative colitis: Evaluation from the Phase 2 study of upadacitinib (U-ACHIEVE)

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.275 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S210-S211

Author(s):

V Jairath ◽

W J Lee ◽

W Zhou ◽

G Heap ◽

J Butler ◽

...

Keyword(s):

Ulcerative Colitis ◽

Disease Activity ◽

Financial Support ◽

Missing Values ◽

Mucosal Inflammation ◽

Controlled Study ◽

Physician Global Assessment ◽

Double Blind ◽

Faecal Calprotectin ◽

Reactive Protein

Abstract Background Several histologic indices are available for evaluating mucosal inflammation activity in ulcerative colitis (UC), although there is no consensus regarding which is the most appropriate for evaluating disease activity in clinical trials. Methods The correlation of three histologic indices, the Geboes Score (GS, range of major grade 0 to 5), Robarts Histopathology Index (RHI, range 0 to 33), and Nancy Index (NI, range grade 0 to grade 4) were evaluated in a Phase 2b, multicenter, randomised, double-blind, placebo-controlled study of upadacitinib in patients with moderately to severely active UC. Biopsy data were collected and centrally read using GS at Baseline and week 8; scores of RHI1 and NI2 were derived based on GS. Descriptive statistics, correlational analyses, and stratified analyses were performed in the pooled study population using as observed data. Results Among 250 UC patients enrolled at Baseline, 224, 214, 209 patients with non-missing values of GS, RHI and NI were observed, respectively. At week 8, the GS, RHI, and NI correlated strongly to each other (r = 0.90 to 0.98), and these 3 indices correlated highly with the subgrade of lamina propria neutrophils, erosion or ulceration, neutrophils in the epithelium, and chronic inflammatory infiltrate (Table 1). The Mayo endoscopic subscore (r = 0.62) was found to have higher correlation with GS, RHI and NI, followed by physician global assessment subscore (r = 0.48 to 0.51), rectal bleeding subscore (r = 0.36 to 0.39) and stool frequency subscore (r = 0.31 to 0.33). Faecal calprotectin (r = 0.47 to 0.50) and C-reactive protein (0.36 to 0.39) and total IBDQ score (r = 0.34 to 0.38) were moderately correlated with GS, RHI, and NI. Over 50% of patients with Mayo endoscopic subscore ≤1 were observed among patients scoring GS = 0 (24/41, 59%), GS = 1 (8/15, 53%), GS = 2 (13/26, 50%), RHI≤3 (45/82, 55%), and NI = 0 (40/69, 58%) at week 8. Conclusion In a moderately to severely active UC population, GS, RHI and NI correlate strongly with each other. Higher correlations were found between histologic scores and endoscopic activity than symptom-related disease activity. Further studies are warranted to evaluate the relationship between histological inflammation and long-term clinical outcomes. References Acknowledgements and Funding statement: Design, study conduct, and financial support for the study were provided by AbbVie; Financial support for the study was provided by AbbVie. AbbVie participated in interpretation of data, review, and approval of the abstract. All authors contributed to development of the abstract and maintained control over final content.

Download Full-text

Exploring the therapeutic potential of sodium benzoate in acetic acid-induced ulcerative colitis in rats

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2019-0086 ◽

2019 ◽

Vol 30 (5) ◽

Author(s):

Deepali Walia ◽

Gurpreet Kaur ◽

Amteshwar Singh Jaggi ◽

Anjana Bali

Keyword(s):

Ulcerative Colitis ◽

Acetic Acid ◽

Protective Effect ◽

Disease Activity ◽

Sodium Benzoate ◽

Therapeutic Potential ◽

Repeated Administration ◽

Therapeutic Agents ◽

Mucosal Inflammation ◽

Acid Infusion

AbstractBackgroundUlcerative colitis is a chronic mucosal inflammation of the large intestine mainly affecting the colon and rectum. The lack of effective and safe therapeutic agents led to the identification of new therapeutic agents to effectively manage the symptoms and complications of ulcerative colitis. The present study aimed to evaluate the protective effect of sodium benzoate in acetic acid-induced ulcerative colitis in rats.MethodsInfusion of 3% acetic acid in the colon through the rectum was done to construct a rat model of ulcerative colitis. After 5 days of infusion, macroscopic, biochemical, and histopathological examinations and disease activity scoring of the colon were done to assess colonic damage.ResultsAcetic acid infusion resulted in severe inflammation in the colon assessed macroscopically and histopathologically. Moreover, it also led to increase in myeloperoxidase (MPO) and reduction in glutathione (GSH) levels. In the present study, repeated administration of sodium benzoate (400 and 800 mg/kg i.p.) and sulfasalazine (500 mg/kgorally) for 7 days, i.e. 2 days before and continued for 5 days after acetic acid infusion, significantly attenuated macroscopic damage and disease activity score as compared to disease control. Further, it also significantly reduced the levels of MPO and enhanced colonic levels of reduced GSH. However, the lower dose of sodium benzoate (200 mg/kg) did not show sufficient protective effect in acetic acid-induced ulcerative colitis. Further, sodium benzoateper sedid not show any effect in normal rats.ConclusionsThe observed protective effect of sodium benzoate may be due to its antioxidant and anti-inflammatory activities in an ulcerative colitis model.

Download Full-text

Correlation of Patient-Reported Outcome (PRO-2) with Endoscopic and Histological Features in Ulcerative Colitis and Crohn’s Disease Patients

Gastroenterology Research and Practice ◽

10.1155/2020/2065383 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Sanja Dragasevic ◽

Aleksandra Sokic-Milutinovic ◽

Milica Stojkovic Lalosevic ◽

Tamara Milovanovic ◽

Srdjan Djuranovic ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Scoring System ◽

Patient Reported Outcome ◽

Patient Reported ◽

Inflammatory Bowel

Background and Objectives. Determination of inflammatory bowel disease activity determines further therapeutic approach and follow-up. The aim of our study was to investigate correlation between patients’ reported symptoms and endoscopic and histological disease activity. Methods. A cross-sectional study was conducted in consecutive newly diagnosed patients with inflammatory bowel disease in a tertiary care referral center. The initial evaluation included patient-reported outcome for stool frequency subscore and rectal bleeding. Endoscopic activity was determined using the Mayo scoring system for ulcerative colitis and the Simple Endoscopic Score for Crohn’s disease. Histopathological activity was assessed using a validated numeric scoring system. Results. We included 159 patients (63 Crohn’s disease with colonic involvement and 96 with ulcerative colitis). We found significant correlation between the Mayo endoscopic subscoring system and histology activity in ulcerative colitis, while no correlation was found in patients with Crohn’s disease. Patient-reported outcome showed inverse correlation with endoscopic and histological activity in Crohn’s disease (rs=−0.67; rs=−0.72), while positive correlation was found in ulcerative colitis (rs=0.84; rs=0.75). Interpretation and Conclusions. Patient-reported outcome is a practical and noninvasive tool for assessment of disease activity in ulcerative colitis patients but not in Crohn’s disease.

Download Full-text

A simple clinical colitis activity index

Gut ◽

10.1136/gut.43.1.29 ◽

1998 ◽

Vol 43 (1) ◽

pp. 29-32 ◽

Cited By ~ 692

Author(s):

R S Walmsley ◽

R C S Ayres ◽

R E Pounder ◽

R N Allan

Keyword(s):

Ulcerative Colitis ◽

Disease Activity ◽

Activity Index ◽

Laboratory Data ◽

Scoring Systems ◽

Initial Assessment ◽

Mucosal Inflammation ◽

Clinical Criteria ◽

Complex Index ◽

Simple Index

Background—The appropriate medical treatment of patients with ulcerative colitis is determined largely by the severity of symptoms. Hospital assessment of the severity of disease activity includes investigation of laboratory indices and sigmoidoscopic assessment of mucosal inflammation.Aims—To develop a simplified clinical colitis activity index to aid in the initial evaluation of exacerbations of colitis.Methods—The information for development of the simple index was initially evaluated in 63 assessments of disease activity in patients with ulcerative colitis where disease activity was evaluated using the Powell-Tuck Index (which includes symptoms, physical signs, and sigmoidoscopic appearance). The new index was then further evaluated in 113 assessments in a different group of patients, by comparison with a complex index utilising clinical and laboratory data, as well as five haematological and biochemical markers of disease severity.Results—The newly devised Simple Clinical Colitis Activity Index, consisting of scores for five clinical criteria, showed a highly significant correlation with the Powell-Tuck Index (r=0.959, p<0.0001) as well as the complex index (r=0.924, p<0.0001) and all laboratory markers (p=0.0003 to p<0.0001).Conclusions—This new Simple Colitis Activity Index shows good correlation with existing more complex scoring systems and therefore could be useful in the initial assessment of patients with ulcerative colitis.

Download Full-text

P130 Faecal calprotectin is a reliable tool to assess endoscopic activity in ulcerative colitis except for short-extent proctitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.259 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S202-S202

Author(s):

R Collin ◽

R Minet-Quinard ◽

L Blayac ◽

L Manlay ◽

B Pereira ◽

...

Keyword(s):

Ulcerative Colitis ◽

False Negative ◽

Vascular Pattern ◽

Endoscopic Evaluation ◽

Faecal Calprotectin ◽

Factors Associated ◽

Non Invasive ◽

Reliable Tool ◽

Mayo Score ◽

Calprotectin Level

Abstract Background Faecal calprotectin (Fcal) is now considered a reliablebiomarker of endoscopic inflammatory activity in patients with ulcerative colitis (UC). However, this biomarker remains imperfect with some false negative in some clinical situations. We aimed to search for endoscopic factors associated with faecal calprotectin level in patients with UC and to identify situations in which this tool might be less efficient. Methods From a database collecting consecutively all the patients with IBD with at least one Fcal dosage in our centre between June 2016 and June 2018, we included all patients who had an endoscopic evaluation within the month before or after dosing without intervention therapeutic during this interval. Fcal level was measured by immuno-chemiluminescence in all patients. Results One hundred and thirty-four patients were included (E1 in 12 patients (9.0%), E2 in 69 patients (51.5%) and E3 in 53 of them (39.5%)). There was a significant correlation between the UCEIS score and Fcal level (r = 0.55, p > 0.001). Fcal level was significantly associated with endoscopic Mayo score with higher values in severe cases (Mayo 0: 32 [15.5–75.3], Mayo 1: 119 [48.0–634.0], Mayo 2: 773 [150.8–1965.0] and Mayo 3: 1200 [572.0–3717.5] μg/g; p < 0.01 for all comparisons). Using an ROC curve, we have defined the best CF thresholds to define an endoscopic Mayo> 1. The performances are presented in the Table 1. In the same way, 100 μg/g was the best Fcal threshold to define a remission endoscopic (endoscopic Mayo score = 0): sensitivity = 79.3% [66.6%–86.3%], specificity = 88.9% [65.3%–98.6%], PPV = 97.9% [92.5%–99.7%], VPN = 40% [24.9%–56.7%]. In multivariate analysis, endoscopic factors associated with the values of CF are: the UCEIS sub-score – vascular pattern (p = 0.001), the UCEIS sub-score – ulcerations (p = 0.013) and the extent of the disease (p = 0.009). CF level in patients with endoscopic Mayo 0 or 1 is lower in the case of low proctitis (<5 cm) than in the case of more extensive RCH (45.5 [19.5–90.5] vs. 214.5 [71.5–730], p < 0.001). While the values of CF were significantly correlated with UCEIS score in patients with proctitis >5 cm (ρ = 0.3665, p < 0.001), they were not low rectal (<5 cm) (ρ = 0.1571, p = 0.71). Conclusion CF is a reliable tool for indirect and non-invasive assessment of activity endoscopic inflammatory disease in UC. Fcal is mainly influenced by severity and extent of the lesions. Its use should be careful in case of proctitis under 5 cm, a situation in which its performances are more questionable.

Download Full-text

Assessing Histological Inflammatory Activity in Patients With Ulcerative Colitis: A Diagnostic Accuracy Study Testing Fecal Biomarkers Lactoferrin and Calprotectin

Crohn's & Colitis 360 ◽

10.1093/crocol/otaa053 ◽

2020 ◽

Vol 2 (3) ◽

Author(s):

Jost Langhorst ◽

Lana Kairey ◽

Angela Oberle ◽

James Boone ◽

Gustav Dobos ◽

...

Keyword(s):

Ulcerative Colitis ◽

Diagnostic Accuracy ◽

Disease Activity ◽

Predictive Value ◽

Diagnostic Accuracy Study ◽

Accuracy Study ◽

Histological Indices ◽

Grade 3 ◽

Histological Remission ◽

Fecal Biomarkers

Abstract Background and Aims Histological remission has arisen as the optimal treatment outcome in ulcerative colitis (UC). The aim of this retrospective study was to explore the diagnostic performance of the noninvasive fecal biomarkers calprotectin (FC) and lactoferrin (FL) compared to the histological indices Nancy Index (NI) and Riley Index (RI). Methods This study is a retrospective diagnostic accuracy study based on secondary analysis of patient data from 2002 to 2017 extracted from medical registries of our clinics in Essen-Mitte, Germany. Patients with UC underwent a colonoscopy, with biopsies taken from the rectum and the sigmoid scored by 2 experienced pathologists according to NI and RI and provided a stool sample within 7 days pre- or post-colonoscopy. Diagnostic accuracy of recommended cutoffs for FC (>50 μg/g) and FL (≥7.25 μg/g) were tested against our reference standard (NI ≥2) in terms of specificity, sensitivity, positive predictive value, negative predictive value, and accuracy (effectiveness). Results The number of patients with UC recruited was n = 226, aged 45.2 (SD 13.3). Histological indices were highly correlated (r = 0.980, P < 0.001). Fecal biomarkers correlated moderately with NI (FC: r = 0.383, P < 0.001; FL: r = 0.420, P < 0.001) and RI (FC: r = 0.395, P < 0.001; FL: r = 0.424, P < 0.001). Fecal biomarker concentrations were increased in patients with active histological disease (NI ≥2), median [IQR], FC 69.72 [20.07–254.38], FL 18.59 [6.06–44.42], compared to those with inactive disease (NI ≤1), FC 12.35 [3.89 – 32.16], FL 3.14 [0.75–11.05], z = −6.60, P < 0.001. Fecal biomarker concentrations differed significantly across NI grades 0–4 (FC: H4 = 45.2; FL: H4 = 47.5, both P < 0.001). Patients with grade 0 had significantly lower concentrations of fecal biomarkers than those with grade 3 (median; FC 10.94 vs 72.22; FL 2.30 vs 29.10; both P < 0.001) or grade 4 (FC 10.94 vs 67.00; FL 2.30 vs 27.64; both P < 0.001), as well as grade 2 for FC only (10.94 vs 56.22, P = 0.001). Concentrations were also lower in patients with grade 1 compared to those with grade 3 (FC 17.49 vs 72.22; FL 4.24 vs. 29.10; both P ≤ 0.001) or grade 4 (FC 17.49 vs 67.00; FL 4.24 vs 27.64; both P < 0.001). Receiver operating characteristics area under the curve showed moderate diagnostic accuracy for both FC 0.76 (95% confidence interval [CI] 0.70–0.83) and FL 0.73 (95% CI 0.66–0.80). Optimized cutoffs for both FC (≥34.29) and FL (≥5.85 μg/g) had slightly improved accuracy, compared with the manufacturer’s cutoffs (FC: 69.9% vs 65.9%; FL: 71.7% vs 69.0%). Conclusions Fecal biomarkers calprotectin and lactoferrin correlate with histological disease activity and differentiate between patients in histological remission from those with evidence of moderate to severe disease activity. Their noninvasiveness, in addition to being inexpensive, supports their use in the clinical monitoring of patients with UC.

Download Full-text