Fecal Calprotectin Predicts Relapse and Histological Mucosal Healing in Ulcerative Colitis
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Abstract:
Mucosal healing in ulcerative colitis leads to a decreased need for medication and decreased risk of disease relapse and colectomy. Histological healing seems to improve the disease prognosis even further. An assessment of both endoscopic and histological mucosal healing requires endoscopy, and the need for a reliable noninvasive biomarker to predict disease relapse is obvious.Seventy patients were included and followed up for 12 months. Inclusion criteria were a total Mayo score ≤1 and a Mayo endoscopic score = 0. The patients underwent sigmoidoscopy with rectal biopsies. Fecal calprotectin (FC) was measured 2 to 3 days before the sigmoidoscopy. The tissue samples were evaluated for neutrophilic inflammation. We aimed at testing the predictive performance of FC and histological inflammatory activity on disease relapse.A baseline FC level of more than 321 mg/kg predicted disease relapse at both the 6- and 12-month follow-ups. Histological inflammatory activity, C-reactive protein, or length of remission was not predictive of relapse. Of note, 11.8% of all patients had histological inflammatory activity despite endoscopic remission and were found to have a higher level of FC (236.5 versus 56 mg/kg, P = 0.02). A receiver operating characteristic analysis estimated a cutoff level of ≤40.5 mg/kg for FC (area under the curve, 0.755 and confidence interval 95%, 0.5895-0.9208) for predicting a histological inflammatory activity score of 0.FC measurements can be used to identify patients with increased risk of relapse after 6 and 12 months and to predict histological mucosal healing. Regular measurement of FC may alter disease monitoring and improve prognosis, and may decrease the need for endoscopy.Keywords:
Sigmoidoscopy
AIM:To explore rectal nitric oxide (NO) as biomarker of treatment response in ulcerative colitis (UC) and Crohn's disease (CD), and examine relationships between rectal NO, mucosal expression of NO synthases (NOS), and pro-inflammatory cytokines. METHODS:Twenty-two patients with UC and 24 with CD were monitored during steroid treatment.Rectal NO levels were measured and clinical activities were assessed on days 1, 3, 7 and 28.Mucosal presence of NOS and pro-inflammatory cytokines were analyzed by immunohistochemistry and RT-PCR. RESULTS:Active UC and CD displayed markedly increased rectal NO levels (10 950 ± 7610 and 5 040 ± 1 280 parts per billion (ppb), respectively) as compared with the controls (154 ± 71 ppb, P < 0.001).Rectal NO correlated weakly with disease activity in both UC and CD (r = 0.34 for UC and r = 0.48 for CD, P < 0.01).In 12 patients, a steroid-refractory course led to colectomy.These patients had only slightly increased NO levels (UC: 620 ± 270 ppb; CD: 1260 ± 550 ppb) compared to those with a therapeutic response (UC: 18 860 ± 530 ppb, P < 0.001; CD: 10 060 ± 3200 ppb, P < 0.05). CONCLUSION:Rectal NO level is a useful biomarker of treatment response in IBD as low NO levels predicts a poor clinical response to steroid treatment.
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Background and aims: Despite promising results, only a few studies have been published on serum calprotectin as a biomarker in IBD. Recently, plasma measurements of calprotectin have been shown to be more reliable than serum measurements. In this study, we aim to assess plasma and serum calprotectin measurements as biomarkers of disease activity in paediatric and adult ulcerative colitis.Methods: Paediatric (5–18 years) and adult (>18 years) patients scheduled for colonoscopy due to suspected or confirmed ulcerative colitis were included prospectively. Stool and blood samples were collected at time of colonoscopy and patient symptom scores were recorded. At colonoscopy the Ulcerative Colitis Endoscopic Index of Severity was recorded. Histology was graded according to the Geboes score.Results: 84 patients where included; 30 paediatric and 54 adult patients. Plasma calprotectin had a stronger correlation to all outcome variables than serum calprotectin. Plasma calprotectin correlated positively to disease extent (Rho = 0.53, p < .0001), symptoms scores (Rho = 0.54, p = .002, only in the paediatric cohort), endoscopic scores (Rho = 0.39, p = .0003), histological scores (Rho 0.28, p = .01) and, when using endoscopic assessment of severity as reference, could discriminate active disease from patients in remission (p = .03).Conclusions: While more studies are needed to assess if plasma calprotectin can discriminate healthy individuals from ulcerative colitis, this study indicates that plasma calprotectin can be used as a biomarker of disease activity, especially in cases where faecal calprotectin measurements are cumbersome either due to patient compliance or logistical requirements.
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Thirty five adult patients with precirrhotic primary sclerosing cholangitis were randomly allocated to treatment for at least one year with low dose (4.1 mg/kg/day) cyclosporin or placebo in a double blind trial. Thirty patients had coexisting ulcerative colitis, including three who had previously undergone colectomy and one who discontinued treatment after three months. Of the remaining 26 patients, 16 received cyclosporin and 10 received placebo. Endoscopy was performed at entry to confirm the diagnosis of inflammatory bowel disease. The ulcerative colitis disease activity was prospectively classified annually as remission/mild, moderate, or severe using the Truelove and Witt9s criteria. Before treatment there were no differences between the cyclosporin and placebo groups in the number of patients with remission/mild colitis, 14/16 (88%) v 9/10 (90%), and moderate colitis, 2/16 (12%) v 1/10 (10%). During treatment, a remission/mild disease course was present in 15/16 (94%) v 6/10 (60%), p = 0.05 and a moderate disease course in 1/16 (6%) v 4/10 (40%), p = 0.05. It is concluded that patients treated with cyclosporin for primary sclerosing cholangitis who have coexisting ulcerative colitis have a more benign course of colitis resulting both from improvement of moderately active colitis and from fewer flares of remission/mildly active colitis. These findings suggest that cyclosporin may be of benefit to the colon in patients with ulcerative colitis who are being treated with cyclosporin for primary sclerosing cholangitis.
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Ulcerative colitis(UC) is a common intestinal disease.The current diagnosis mainly rely on colonoscopy,but during the colonoscopy check,patients suffered from pain.In this artical,we will review the latest testing index that calprotectin(CP) plays a role in the diagnosis of UC.
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. The activity of a non-invasive marker of inflammation in the colon is used to evaluate the clinical, endoscopic and biological characteristics of ulcerative colitis and colon polyps. In this study, the authors studied the possibility of using non-invasive marker – a faecal calprotectin as a highly sensitive method in the activity of the inflammatory process in the colon. The study included 40 patients with ulcerative colitis and colon polyps, which a colonoscopy was performed. The concentration of calprotectin in stool samples was determined in all patients and was evaluated according to the clinical activity of the disease. A significant increase in the level of calprotectin in patients with colon polyps 42±5,6 µg/g wasn’t revealed. On the contrary, the concentration of a faecal calprotectin was significantly higher in patients with ulcerative colitis. This concentration increases in patients with a high degree of inflammatory activity and length of lesions of the mucous membrane of the colon. The concentration of calprotectin level correlates with the extent of lesion and activity of the inflam-matory process in the colon, but not with endoscopic activity of ulcerative colitis. The use of modern method of non-invasive diagnostic marker of the inflammatory process in the intestine allows to diagnose functional and organic pathologies of the colon without the supplementary instrumental methods.
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To assess intestinal inflammation, simple, inexpensive and objective tools are desirable in inflammatory bowel disease. This study aimed to evaluate fecal calprotectin as a marker of active disease in ulcerative colitis.Sixty patients with a diagnosis of ulcerative colitis and 20 controls were recruited into the study. The disease activity of ulcerative colitis was determined by modified Truelove-Witts criteria and Rachmilewitz endoscopic index. The enzyme-linked immunosorbent assay was used to measure the concentrations of fecal calprotectin. C-reactive protein, erythrocyte sedimentation rate and hemogram were also measured, and inflammatory markers were compared with fecal calprotectin in determining disease activity.Fecal calprotectin concentration in the patients with active ulcerative colitis (n=30) was significantly higher than that in the inactive ulcerative colitis group (n=30) and in the controls (n=20) (95% confidence interval: 232.5 (0.75-625) vs 11.7 (0.2-625), 7.5 (0.5-512) mg/L, p<0.001). There was no significant difference between the patients with inactive ulcerative colitis and controls (p>0.05). The calprotectin concentration was greater in the patients with a more severe clinical index, higher endoscopic activity (>4), elevated C-reactive protein, leukocytosis, and extensive colitis (p<0.05). The areas under the curve of the receiver operating characteristics were 0.817, 0.809, 0.532, and 0.507 for C-reactive protein, fecal calprotectin, leukocyte count, and erythrocyte sedimentation rate, respectively. There was a significant correlation between the fecal calprotectin concentration and the endoscopic activity in ulcerative colitis (r = 0.548, p<0.001).Fecal calprotectin is a useful marker in the diagnosis of active disease and evaluation of clinical and endoscopic activity in ulcerative colitis.
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It has been shown that fecal calprotectin can be used to evaluate mucosal inflammation better than using clinical indices and serum markers. The aim of this study was to assess the use of fecal calprotectin for evaluating the disease activity in 2 groups of patients with ulcerative colitis and a control group. The study population consisted of 30 patients with active-phase ulcerative colitis, 30 remission-phase patients, and 30 healthy control patients. After obtaining informed consent, we took blood and fecal samples. Fecal calprotectin was assessed by the enzyme-linked immunosorbent assay method; levels of more than 200 μg/g were considered abnormal. The Simple Clinical Colitis Activity Index was used to evaluate disease activity. A one-way analysis of variance test and a Pearson correlation test were used to analyze the results. The means ±SD of the disease activity index were 4 ± 2.8, 6 ± 1.9, and 2.7 ± 2.5 in patients with active-phase and remission-phase ulcerative colitis, respectively (p < .001). Fecal calprotectin (μg/g) values (mean ±SD) for active-phase patients, remission-phase patients, and the control group patients were significantly different: 711.7 ± 228, 517 ± 328.2, and 304 ± 297.5, respectively. There was a significant correlation between fecal calprotectin and the disease activity index values (r = .41; p = .004). Fecal calprotectin could be a useful tool in assessing the bowel disease activity in patients with ulcerative colitis.
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Mucosal healing has become the new goal of treatment in ulcerative colitis. Fecal calprotectin has been demonstrated to differentiate between mucosal inflammation and mucosal healing. With this project, we investigated whether a reduction in f-calprotectin to <250 μg/g after medical treatment for active ulcerative colitis could predict mucosal healing.After a baseline colonoscopy, 20 patients with active ulcerative colitis were followed with consecutive fecal calprotectin monthly until two measurements of fecal calprotectin < 250 μg/g or a maximum follow-up of 12 months. A flexible sigmoidoscopy was then performed and Mayo endoscopic subscore was used to evaluate degree of inflammation. Simple Clinical Colitis Activity Index was used for evaluation of clinical disease activity.A total of 16 patients achieved fecal calprotectin < 250 μg/g during follow-up, and all 16 patients had endoscopic mucosal healing (Mayo endoscopic subscore of ≤1) on the second endoscopy. The remaining four patients had persistently high f-calprotectin levels before the second endoscopy with Mayo endoscopic subscore corresponding to endoscopic mucosal healing in three out of four patients.Fecal calprotectin <250 μg/g after medical treatment for active ulcerative colitis is a reliable marker of endoscopic mucosal healing.
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The data of 301 ulcerative proctitis/colitis patients, with a mean follow-up of 10 (1/2-26) years were analysed retrospectively. In 84 patients (28%) the diagnosis was made in this hospital (non-selected group), the other 217 patients were referred from other hospitals with an established diagnosis of ulcerative colitis. At any time after the fifth year of illness approximately 55% of the non-selected patients were free of symptoms, for the referred patients this proportion was 30%. In one half of the cases the inflammation started as a proctitis, almost 60% of these progressed to colitis later. Fourteen patients (5%) had a toxic megacolon, and a colon carcinoma developed in 9 patients (3%) on average 13 years after the first symptoms of colitis. We recorded 9 colitis-related deaths. Fifty patients (17%) underwent a colectomy, mostly because of failure of conservative therapy.
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Sigmoidoscopy
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Background and Study Aim: Ulcerative colitis (UC) is a chronic, idiopathic inflammatory bowel disease characterized by remission of disease activity. Searching for laboratory markers which are simple, sensitive, specific and noninvasive is fundamental to assess the extent of inflammation, activity of the disease, evolution and prognosis which can be used to assess response to treatment and the possibility of relapse. Our aim of the work was to investigate the diagnostic role of fecal calprotectin and serum MMP-9 in determining the activity of ulcerative colitis. Patients and Methods: 71 patients were included in the study and fecal calprotectin, serum MMP-9, ESR and CRP were measured in these patients to determine the disease activity of ulcerative colitis. Results: Fecal calprotectin concentration in the patients with active UC was significantly higher than that in inactive disease and in controls (387.21 ± 44.07 μg/g vs 103.62 ± 119.67 μg/g, 12.44 ± 3.65 μg/g, p = 0.000). Serum MMP-9 was found to be higher in patients with active UC than in patients with inactive disease (11.02 ± 5.29 vs 4.01 ± 1.72 ng/ml, p = 0.000). A significant difference was also found in the patients with active UC of mild, moderate and severe degrees. Also, strong positive correlation was found between fecal calprotectin and serum MMP-9 and the severity of the disease. The area under the curve of the receiver operating characteristics (AUCROC) was 0.949 and 0.941 for fecal calprotectin and serum MMP-9 respectively. Conclusion: Fecal calprotectin and serum MMP-9 can be used to differentiate between active and inactive forms of UC.
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