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Faecal calprotectin for differentiating between irritable bowel syndrome and inflammatory bowel disease: a useful screen in daily gastroenterology practice.

ABSTRACT: To determine the best faecal calprotectin (FCP) cut-off level for differentiating between irritable bowel syndrome (IBS) and organic disease, particularly inflammatory bowel disease (IBD), in patients presenting with chronic diarrhoea.Retrospective analysis of patients who had colonoscopy, histology and FCP completed within 2 months.District general hospital.Consecutive new patients with chronic diarrhoea lasting longer than 4 weeks.Patients were seen by a single experienced gastroenterologist and listed for colonoscopy with histology. Laboratory investigations included a single faecal specimen for calprotectin assay (lower limit of detection: 8 µg/g), the results used for information only.Six FCP cut-off levels (range 8-150 µg/g) were compared against the 'gold standard' of histology: inflammation 'present' or 'absent'.Of 119 patients studied, 98 had normal colonoscopy and histology. The sensitivity of FCP to detect IBD at cut-off levels 8, 25 and 50 µg/g was 100% (with corresponding specificity 51%, 51%, 60%). In contrast, the lowest FCP cut-off, 8 µg/g, had 100% sensitivity to detect colonic inflammation, irrespective of cause (with negative predictive value (NPV) 100%). Importantly, 50/119 patients (42%) with FCP <8 µg/g had normal colonoscopy and histology.Our results suggest that using FCP to screen patients newly referred for chronic diarrhoea could exclude all without IBD and, at a lower cut-off, all without colonic inflammation, thus avoiding the need for colonoscopy. Such a major reduction has implications for resource allocation.

SUBMITTER: Banerjee A

PROVIDER: S-EPMC5369552 | biostudies-other | 2015 Jan

REPOSITORIES: biostudies-other

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Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Irritable Bowel Syndrome (IBS).

Project description:Background & aimsIrritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders, affecting about 10% of the general population globally. The aim of this consensus was to develop guidelines for the management of IBS.MethodsA systematic literature search identified studies on the management of IBS. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a multidisciplinary group of clinicians and a patient.ResultsConsensus was reached on 28 of 31 statements. Irritable bowel syndrome is diagnosed based on symptoms; serological testing is suggested to exclude celiac disease, but routine testing for C-reactive protein (CRP), fecal calprotectin or food allergies is not recommended. A trial of a low fermentable oligosaccharides, disaccharides, monosaccharides, polyols (FODMAP) diet is suggested, while a gluten-free diet is not. Psyllium, but not wheat bran, supplementation may help reduce symptoms. Alternative therapies such as peppermint oil and probiotics are suggested, while herbal therapies and acupuncture are not. Cognitive behavioural therapy and hypnotherapy are suggested psychological therapies. Among the suggested or recommended pharmacological therapies are antispasmodics, certain antidepressants, eluxadoline, lubiprostone, and linaclotide. Loperamide, cholestyramine and osmotic laxatives are not recommended for overall IBS symptoms. The nature of the IBS symptoms (diarrhea-predominant or constipation-predominant) should be considered in the choice of pharmacological treatments.ConclusionsPatients with IBS may benefit from a multipronged, individualized approach to treatment, including dietary modifications, psychological and pharmacological therapies.

| S-EPMC6507291 | biostudies-literature

Measurement of faecal calprotectin and lactoferrin in inflammatory bowel disease.

Project description:Crohn's disease and ulcerative colitis are chronic relapsing gastrointestinal conditions characterised by an influx of inflammatory cells to the affected gut mucosa. The mainstay of diagnosing and re-evaluating these conditions in clinical practice and research is by invasive serological, radiological, endoscopic and histological assessment. In clinical trials, disease activity is often evaluated using a combination of the above tests plus clinical indices such as the Crohn's Disease Activity Index and Ulcerative Colitis Activity Index. These tools rely on subjective assessment of symptoms and so, often, do not correlate with mucosal inflammation or mucosal healing, which may be the preferred therapeutic end point for long-term inflammatory bowel disease (IBD) management. The faecal biomarkers calprotectin and lactoferrin are neutrophil derived proteins that are stable in faeces and can be detected by quantitative ELISA in small stool samples. Concentrations of both are raised in patients with gastrointestinal mucosal inflammation. They provide a unique, inexpensive, non-invasive method of testing for active inflammatory disease. They can be used to screen for IBD and as a surrogate marker of mucosal healing they are useful in monitoring the response to therapeutic intervention or surgery. They may also predict the clinical course of the disease. This clinical review aims to discuss the current evidence, limitations and potential future uses of these biomarkers in IBD.

| S-EPMC3724198 | biostudies-other

Faecal haemoglobin and faecal calprotectin as indicators of bowel disease in patients presenting to primary care with bowel symptoms.

Project description:ObjectiveIn primary care, assessing which patients with bowel symptoms harbour significant disease (cancer, higher-risk adenoma or IBD) is difficult. We studied the diagnostic accuracies of faecal haemoglobin (FHb) and faecal calprotectin (FC) in a cohort of symptomatic patients.DesignFrom October 2013 to March 2014, general practitioners were prompted to request FHb and FC when referring patients with bowel symptoms to secondary care. Faecal samples were analysed for haemoglobin (EIKEN OC-Sensor io) and calprotectin (BÜHLMANN Calprotectin ELISA). Patients triaged to endoscopy were investigated within 6?weeks. All clinicians and endoscopists were blind to the faecal test results. The diagnostic accuracies of FHb and FC for identification of significant bowel disease were assessed.Results1043 patients returned samples. FHb was detectable in 57.6% (median 0.4?µg/g, 95% CI 0.4 to 0.8; range 0-200). FC at 50?µg/g or above was present in 60.0%. 755 patients (54.6% women, median age 64?years (range 16-90, IQR 52-73)) returned samples and completed colonic investigations. 103 patients had significant bowel disease; the negative predictive values of FHb for colorectal cancer, higher-risk adenoma and IBD were 100%, 97.8% and 98.4%, respectively. Using cut-offs of detectable FHb and/or 200?µg/g FC detected two further cases of IBD, one higher-risk adenoma and no additional cancers.ConclusionsIn primary care, undetectable FHb is a good 'rule-out' test for significant bowel disease and could guide who requires investigation.

| S-EPMC5036251 | biostudies-literature

Compliance with the faecal calprotectin test in patients with inflammatory bowel disease.

Project description:We investigated, for the first time, levels of compliance with faecal calprotectin test in inflammatory bowel disease patients.All consecutive adult inflammatory bowel disease patients having been prescribed an faecal calprotectin test between December 2014-July 2015 were included. At their next visit to the hospital, patients had to return a stool sample for the faecal calprotectin test and answer a simple questionnaire: 'Have you brought a stool sample? If not, why not? If so, did you encounter any difficulties when collecting the sample? Were you aware of faecal calprotectin before being asked to take the test?'.One hundred and one patients were included (50 men; 77 patients with Crohn's disease). The range age was 40 years (19-68). Eighty-nine patients were being treated with infliximab, 10 were on vedolizumab, and two were not being treated with a biologic. Thirty-seven patients (35%) had performed the faecal calprotectin test. Eighty-one patients (80%) had not been aware of faecal calprotectin before being asked to take the test. Of the 64 patients who did not take the test, the prime reasons for non-compliance were forgetfulness (n = 49, 76.6%), a lack of perceived benefit for the test (n = 7, 11%), constipation (n = 5, 7.8%), refusal to handle faeces (n = 2, 3.1%), and difficulty collecting the stool sample (n = 1, 1.5%).Only one-third of the patients performed the faecal calprotectin test. The main reason for non-compliance was forgetfulness. Our present results emphasise the need for better patient education on the importance of complying with faecal calprotectin testing and the future of faecal calprotectin testing at home.

| S-EPMC5548356 | biostudies-other

Faecal biomarker patterns in patients with symptoms of irritable bowel syndrome.

Project description:To determine rates of faecal biomarker results capable of suggesting potentially treatable causes of irritable bowel syndrome (IBS) symptomatology in a population of patients with symptoms of IBS who meet Rome III criteria for that condition.Descriptive, retrospective study in which faecal biomarker results (dichotomised into 'normal' and 'abnormal' values) were related to data from patient-completed questionnaire data identifying demographics, Rome III criteria for IBS and IBS phenotype (IBS-D, IBS-C, IBS-M and IBS-U).Commercial reference laboratory.Individuals whose physicians ordered faecal biomarker testing for evaluation of chronic abdominal symptoms consistent with IBS.None.Rates of occurrence of abnormal results on any of seven faecal biomarkers suggesting a treatable cause for IBS symptoms.Abdominal symptoms meeting Rome III criteria for IBS were present in 3553 records (the population), which were subjected to further analysis. Abnormal biomarker results (the outcomes) occurred in 94% of cases; 73% and 65% of records indicated growth of a bacterial potential pathogen and low growth of beneficial organisms, respectively. Abnormal results for all other faecal biomarkers occurred with frequencies from 5% to 13%. Frequency of abnormal results for elastase, calprotectin, eosinophil protein X, and beneficial organisms rose significantly with age, and differed significantly across IBS phenotypes.A large proportion of patients manifesting symptoms meeting Rome III IBS diagnostic criteria have faecal biomarker results indicating potential underlying, treatable causes of their symptoms. Faecal biomarker testing is an appropriate means of identifying potentially treatable causes of IBS symptoms.

| S-EPMC5036220 | biostudies-literature

Faecal S100A12 as a non-invasive marker distinguishing inflammatory bowel disease from irritable bowel syndrome.

Project description:ObjectiveS100A12 is a pro-inflammatory protein that is secreted by granulocytes. S100A12 serum levels increase during inflammatory bowel disease (IBD). We performed the first study analysing faecal S100A12 in adults with signs of intestinal inflammation.MethodsFaecal S100A12 was determined by ELISA in faecal specimens of 171 consecutive patients and 24 healthy controls. Patients either suffered from infectious gastroenteritis confirmed by stool analysis (65 bacterial, 23 viral) or underwent endoscopic and histological investigation (32 with Crohn's disease, 27 with ulcerative colitis, and 24 with irritable bowel syndrome; IBS). Intestinal S100A12 expression was analysed in biopsies obtained from all patients. Faecal calprotectin was used as an additional non-invasive surrogate marker.ResultsFaecal S100A12 was significantly higher in patients with active IBD (2.45 +/- 1.15 mg/kg) compared with healthy controls (0.006 +/- 0.03 mg/kg; p<0.001) or patients with IBS (0.05 +/- 0.11 mg/kg; p<0.001). Faecal S100A12 distinguished active IBD from healthy controls with a sensitivity of 86% and a specificity of 100%. We also found excellent sensitivity of 86% and specificity of 96% for distinguishing IBD from IBS. Faecal S100A12 was also elevated in bacterial enteritis but not in viral gastroenteritis. Faecal S100A12 correlated better with intestinal inflammation than faecal calprotectin or other biomarkers.ConclusionsFaecal S100A12 is a novel non-invasive marker distinguishing IBD from IBS or healthy individuals with a high sensitivity and specificity. Furthermore, S100A12 reflects inflammatory activity of chronic IBD. As a marker for neutrophil activation, faecal S100A12 may significantly improve our arsenal of non-invasive biomarkers of intestinal inflammation.

| S-EPMC2095695 | biostudies-literature

Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome.

Project description:About one-third of patients with IBS-diarrhoea (irritable bowel syndrome-D) have evidence of increased bile acid synthesis or excretion.To assess effects of the bile acid sequestrant, colesevelam, on faecal excretion of BAs, hepatic BA synthesis and diarrhoea in IBS-D; to appraise whether individual or random stool samples accurately reflect 48-h total faecal bile acid excretion and proportions of the main bile acids excreted and to study the faecal fat excretion in response to colesevelam.A single-centre, unblinded, single-dose trial of effects of colesevelam, 1875 mg [3 tablets (625 mg tablets)] orally, twice daily, for 10 days on total 48-h faecal bile acid excretion and fasting serum C4 (7?-hydroxy-4-cholesten-3-one; surrogate of hepatic bile acid synthesis). Stool diaries documented bowel functions for 8 days prior and 8 days during colesevelam treatment. Stool 48-h samples and fasting serum were collected for faecal fat, faecal bile acid and serum C4.Colesevelam was associated with significantly increased faecal total bile acid excretion and deoxycholic acid excretion, increased serum C4 and more solid stool consistency. There was a significant inverse correlation between number of bowel movements per week and the total bile acid sequestered into stool during the last 48 h of treatment. Random stool samples did not accurately reflect 48-h total or individual faecal bile acid excretion. Sequestration of bile acids by colesevelam did not increase faecal fat.Colesevelam increases delivery of bile acids to stool while improving stool consistency, and increases hepatic bile acid synthesis, avoiding steatorrhoea in patients with IBS-D. Overall effects are consistent with luminal bile acid sequestration by colesevelam.

| S-EPMC4493894 | biostudies-literature

A Distinct Faecal Microbiota and Metabolite Profile Linked to Bowel Habits in Patients with Irritable Bowel Syndrome.

Project description:Patients with irritable bowel syndrome (IBS) are suggested to have an altered intestinal microenvironment. We therefore aimed to determine the intestinal microenvironment profile, based on faecal microbiota and metabolites, and the potential link to symptoms in IBS patients. The faecal microbiota was evaluated by the GA-mapTM dysbiosis test, and tandem mass spectrometry (GC-MS/MS) was used for faecal metabolomic profiling in patients with IBS and healthy subjects. Symptom severity was assessed using the IBS Severity Scoring System and anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. A principal component analysis based on faecal microbiota (n = 54) and metabolites (n = 155) showed a clear separation between IBS patients (n = 40) and healthy subjects (n = 18). Metabolites were the main driver of this separation. Additionally, the intestinal microenvironment profile differed between IBS patients with constipation (n = 15) and diarrhoea (n = 11), while no clustering was detected in subgroups of patients according to symptom severity or anxiety. Furthermore, ingenuity pathway analysis predicted amino acid metabolism and several cellular and molecular functions to be altered in IBS patients. Patients with IBS have a distinct faecal microbiota and metabolite profile linked to bowel habits. Intestinal microenvironment profiling, based on faecal microbiota and metabolites, may be considered as a future non-invasive diagnostic tool, alongside providing valuable insights into the pathophysiology of IBS.

| S-EPMC8230381 | biostudies-literature

Utility of faecal calprotectin in inflammatory bowel disease (IBD): what cut-offs should we apply?

Project description:Faecal calprotectin (FC), a cytosolic protein released by neutrophils (S100 family) in response to inflammation, is a simple, non-invasive test that can be used to differentiate irritable bowel syndrome (IBS) with inflammatory bowel disease (IBD), where there can be considerable symptom overlap.The aims of the study were (1) to be able to predict the ability of FC to exclude IBD and determine cut-offs when in remission, (2) to investigate the effects of time and temperature on stability of FC and (3) compare three ELISA kits to measure FC: Buhlmann, PhiCal v1 and PhiCal v2. A total of 311 patients with altered bowel habit were tested for FC; 144 with IBS, 148 with IBD and 19 with other organic causes.Sensitivity and specificity of FC (with PhiCal v2 kit) to distinguish between functional disorder (IBS) and IBD using cut-off 50 μg/g were 88% and 78%, respectively, with a negative predictive value of 87%. Area under the receiver operating curve was 0.84 (CI 0.78 to 0.90). For those with IBD, FC values below 250 μg/g corresponded with remission of disease with a sensitivity and specificity of 90% and 76%, respectively. Area under the receiver operating curve was 0.93 (CI 0.89 to 0.97). FC was stable once extracted and frozen for up to 2.5 months. Pearson correlation was good between Buhlmann assay and PhiCal v2 (r2 = 0.95).FC has up to 87% negative predictive value to exclude IBD, and cut-offs less than 250 μg/g had 90% sensitivity to determine remission in IBD. Once frozen, FC is stable and the ELISA monoclonal plates were broadly comparable.

| S-EPMC4283700 | biostudies-other

Cost-effectiveness of faecal calprotectin used in primary care in the diagnosis of inflammatory bowel disease.

Project description:ObjectiveInflammatory bowel disease (IBD) is a chronic, autoimmune, gastrointestinal disorder. Canada has one of the highest prevalence and incidence rates of IBD in the world. Diagnosis is challenging due to the similarity of symptoms to functional gastrointestinal disorders. Faecalcalprotectin (FC) is a biomarker for active mucosal inflammation and has proven effective in the diagnosis of IBD. Our study objective was to assess the cost-effectiveness of adding an FC test compared with standard practice (blood test) in primary care among adult patients presenting with gastrointestinal symptoms.DesignWe constructed a decision analytic tree with a 1-year time horizon. The cut-off level of 100?µg/g was used for FC testing. Probabilistic analyses were conducted for the base case and all scenarios.SettingCanadian health sector perspective.PopulationA hypothetical cohort of adult patients presenting with gastrointestinal symptoms in the primary care setting.InterventionsFC test compared with blood test.Main outcome measuresCosts, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER) of FC test expressed as cost per QALY gained compared with blood test and time to IBD diagnosis.ResultsFC testing is expected to cost more ($C295.1 vs $C273.9) than standard practice but yield little higher QALY (0.751vs0.750). The ICER of FC test was $C20?323 per QALY. Probabilistic analysis demonstrated that at a willingness-to-pay threshold of $C50?000 per QALY, there was 81.3% probability of FC test being cost-effective. The use of FC test in primary care reduced the time to IBD diagnosis by 40.0 days (95% CI 16.3 to 65.3 days), compared with blood testing alone.ConclusionsBased on this analysis of short-term outcomes, screening adult patients in primary care using FC test at a cut-off level of 100?µg/g is expected to be cost-effective in Canada.

| S-EPMC6500206 | biostudies-literature

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