|Year : 2014 | Volume
| Issue : 1 | Page : 35-43
Calprotectin as a fecal marker for diagnosis and follow-up in patients with ulcerative colitis
Mohamed A.E. Nouh1, Atef A.E. Ali1, Emad F.A. El Halim2, Hosam I. Mohamed1, Ayman M.A. El Ghany1, Amira M. Badawy1
1 Department of Tropical Medicine, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menoufiya University, Menoufiya, Egypt
|Date of Submission||10-Jun-2013|
|Date of Acceptance||08-Oct-2013|
|Date of Web Publication||20-May-2014|
Amira M. Badawy
MSc, MahaletSubk, Ashmoon, Menoufiya, 32811
Source of Support: None, Conflict of Interest: None
This study is designed to evaluate the role of fecal calprotectin as a marker for the diagnosis of ulcerative colitis (UC) and its correlation with disease activity and remission.
Inflammatory bowel diseases (IBD) are lifelong intestinal inflammatory conditions of unknown etiology, characterized by remissions and exacerbations. The diagnosis and classification of IBD is usually established by a combination of tests (laboratory, endoscopic, and/or radiologic) in the presence of clinical symptoms. Fecal calprotectin serves as a noninvasive biomarker of intestinal inflammation, and has been found to be useful in the diagnosis of IBD, assessment of response to medical therapy, and in prediction of clinical relapse.
Materials and methods
This study was carried out on 40 patients. Twenty of these patients had clinical, laboratory, colonoscopic, and histopathological findings of UC. Group I was subdivided as follows: GIa: 20 patients with active UC and GIb: the same patients as in GIa while on remission. Group II included 20 patients as controls, matched for age and sex without clinical, laboratory, colonoscopic, and histopathological findings of UC. Complete stool analysis, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) titer, complete blood count, colonoscopy and biopsy, histopathological examination of biopsy specimens, measurement of ulcerative colitis activity index (UCAI), and quantitative determination of calprotectin in stool sample were carried out for all patients.
There was a highly significant increase in the mean value of fecal calprotectin in active UC patients in comparison with the inactive UC patients and controls. Also, there was a highly significant increase in the mean value of fecal calprotectin in the inactive UC patients in comparison with the controls. There was also a highly significant positive correlation between fecal calprotectin and UCAI, CRP, ESR, total leukocyte count, and platelets count. At the cut-off value of 131 μg/g, fecal calprotectin has 100% accuracy, sensitivity, specificity, positive predictive value, and negative predictive value in differentiating UC patients from other patients with lower gastrointestinal symptoms and at the cut-off value of 253 μg/g fecal calprotectin has 95% accuracy, sensitivity, specificity, positive predictive value, and negative predictive value in differentiating active from inactive UC patients.
Fecal calprotectin is a valuable, simple, easily performed, and cost-effective noninvasive marker for evaluation of patients with UC. It differentiated UC and other diseases causing colonic symptoms (cut-off value of 131 μg/g) and between active and inactive UC (cut-off value of 235 μg/g) with high accuracy, sensitivity, and specificity. It also correlates well with other markers for UC activity (UCAI, ESR, CRP, total leukocyte count, and platelets count) and could be a reliable surrogate marker for the severity of UC.
Keywords: Calprotectin, colitis, fecal marker, inflammatory bowel disease, ulcerative colitis
|How to cite this article:|
Nouh MA, Ali AA, El Halim EF, Mohamed HI, El Ghany AM, Badawy AM. Calprotectin as a fecal marker for diagnosis and follow-up in patients with ulcerative colitis. Menoufia Med J 2014;27:35-43
|How to cite this URL:|
Nouh MA, Ali AA, El Halim EF, Mohamed HI, El Ghany AM, Badawy AM. Calprotectin as a fecal marker for diagnosis and follow-up in patients with ulcerative colitis. Menoufia Med J [serial online] 2014 [cited 2021 Mar 5];27:35-43. Available from: http://www.mmj.eg.net/text.asp?2014/27/1/35/132726
| Introduction|| |
Inflammatory bowel diseases (IBD) are lifelong intestinal inflammatory conditions of unknown etiology, characterized by remissions and exacerbations . IBD is comprised of two main distinguishable entities, ulcerative colitis (UC) and Crohn's disease (CD), and IBD-unclassified or indeterminate colitis is a diagnosis that covers the 'gray' zone of diagnostic uncertainty between UC and CD . IBD is a chronic inflammatory disorder that results from a dysregulated immune response in genetically susceptible individuals .
Their pathogenesis is not completely understood, but in both diseases, bowel damage is induced by an uncontrolled activation of both innate and adaptive immunity because of an inappropriate immune response to luminal antigens. This mechanism results in an imbalance between proinflammatory cytokines, interferon gamma, tumor necrosis factor alpha (TNF-͍), interleukin-1 (IL-1), IL-12, and anti-inflammatory mediators, which maintains chronic tissue damage. TNF-͍, produced by macrophages and activated T cells, plays a key role in inducing further stimulation and recruitment of other inflammatory cells .
Significant progress has been made in recent years in the field of IBD epidemiology, pathogenesis, and treatment and a number of new insights have been gained. Also, there is an increasing interest in the discovery of different new aspects related to diagnosis and treatment .
The diagnosis and differentiation of CD or UC is still made on the basis of clinical, radiographic, endoscopic, and histological findings; newer less invasive serological tests are being used to distinguish between these disorders and provide prognostic information to possibly guide therapy .
Laboratory markers have been investigated in IBD for diagnostic and differential diagnostic purposes, assessment of disease activity and risk of complications, prediction of relapse, and monitoring the effect of therapy .
The role played by the distinct biological markers in chronic IBD remains insufficiently characterized .
Calprotectin is a calcium-binding protein secreted predominantly by neutrophils and monocytes. Fecal calprotectin (FC) is a marker for neoplastic and inflammatory gastrointestinal (GI) diseases. The FC test is a simple, noninvasive, rapid and inexpensive diagnostic tool that enables differentiation between GI functional disorders and inflammatory conditions and prediction of relapse in nonspecific IBD .
FC has been proposed as a noninvasive surrogate marker of intestinal inflammation in IBD. This fecal marker can be detected using simple and cheap techniques. FC has a good diagnostic precision for the differentiation of organic and functional intestinal diseases. A high concentration of calprotectin in feces represents a strong argument to carry out a colonoscopy in order to rule out the presence of IBD or other organic pathologies. Parallelism between FC levels and IBD activity has been confirmed, although this fecal marker appears to better reflect the disease activity in UC than in CD. The capacity of FC's to predict relapse of IBDs is promising. It has been suggested that, in IBD patients receiving treatment, a normalization or decrease in FC concentrations is an accurate indicator of endoscopic healing. Greater FC concentration has been found in asymptomatic first-degree relatives of patients with IBD, suggesting that there is a high prevalence of subclinical intestinal inflammation in them .
| Materials and methods|| |
This study was carried out on patients referred to the endoscopy unit and to the outpatient clinic of Tropical Medicine Department in Menoufia University Hospital with complaints of abdominal pain, chronic diarrhea, dysentery, and or bleeding per rectum in the period from January 2010 to November 2012. Of these, 40 patients were selected. Twenty of these patients had clinical, laboratory, colonoscopic, and histopathological findings of UC (group I); there were 11 (55%) men and 9 (45%) women ranging in age from 22 to 55 years, mean age 35.6 years. Group I was subdivided as follows: GIa: 20 patients with active UC and GIb: the same patients as in GIa while on remission. Group II included 20 patients as controls matched for age and sex without clinical, laboratory, colonoscopic, and histopathological findings of UC.
All patients and controls were subjected to the following: full assessment of history, complete clinical examination, laboratory investigations [complete stool analysis, urine analysis, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) titer, complete blood count, prothrombin time, partial thromboplastin time and international normalized ratio, bleeding and coagulation time, fasting and postprandial blood glucose, serum creatinine and blood urea nitrogen, serum albumin, aspartate aminotransferase, alanine aminotransferase, serum bilirubin total and direct], abdominal ultrasonography, abdominal plain radiography, colonoscopy and biopsy, histopathological examination of biopsy specimens, measurement of activity index, quantitative determination of calprotectin in stool samples, and statistical analysis of the results.
FC was measured using the PhiCal Calprotectin ELISA Kit for the in-vitro determination of calprotectin in stool (PhiCal; Immundiagnostik AG [DIAGNOSTIC AUTOMATION / CORTEZ DIAGNOSTICS, INC. 23961 Craftsman Rd. Suite E/F Calabasas, California 91302-2521 USA]).
Extraction of the stool sample
Diluted extraction buffer is used as a sample extraction buffer. The dilution factor of the final stool suspension depends on the amount of stool sample used and the volume of the buffer.
The raw stool sample has to be thawed.
The extraction buffer should be allowed to reach room temperature.
The tube has to be shaken well.
The sample should be allowed to stand for ∼10 min until the sediment has settled. Floating material such as shells of grains can be neglected.
Note that calprotectin in stool is described to be stable for ∼6 days. Nevertheless, we recommend storage of the samples for not more than 48 h at 2-8C. Long-term storage is recommended at −20C. The frozen samples should be allowed to thaw slowly, preferably at 2-8C overnight, and the samples should be warmed to room temperature before analysis.
Principle of the test
The assay utilizes the two-site 'sandwich' technique with two selected monoclonal antibodies that bind to human calprotectin. Standards, controls, and diluted patient samples that are assayed for human calprotectin are added to wells of a microplate coated with a high-affinity monoclonal anti-human calprotectin antibody. During the first incubation step, calprotectin in the samples is bound by the immobilized antibody. Then, a peroxidase-labeled conjugate is added to each well and the following complex is formed: capture antibody-human calprotectin-peroxidase conjugate. Tetramethylbenzidine is used as a substrate for peroxidase. Finally, an acidic stop solution is added to terminate the reaction. The color changes from blue to yellow. The intensity of the yellow color is directly proportional to the calprotectin concentration of the sample. A dose-response curve of the absorbance unit (OD) versus concentration is generated using the values obtained from standard. Calprotectin present in the patient samples is determined directly from this curve.
- All reagents and samples should be thawed to room temperature (18-26C) and mixed well.
- The positions of STD/SAMPLE/CTRL (Standards/Sample/Controls) should be marked in duplicate on a protocol sheet.
- As many microtiter strips as needed should be taken from the kit. The unused strips should be covered at 2-8C. Strips are stable until the expiry date stated on the label.
- A volume of 100 μl of STD/SAMPLE/CTRL (Standard/Sample/Controls) should be added in duplicate to the respective wells.
- The plate should be covered tightly and incubated for 30 min at room temperature (18-26C).
- The contents of each well should be aspirated. Each well should be washed five times with 250 μl of wash buffer. After the final washing step, the inverted microtiter plate should be firmly tapped on an absorbent paper.
- A volume of 100 μl of CONJ (conjugate) should be added to each well.
- The plate should be covered tightly and incubated for 30 min at room temperature (18-26C).
- The contents of each well should be aspirated. Each well should be washed five times with 250 μl of wash buffer. After the final washing step, the inverted microtiter plate should be tapped firmly on an absorbent paper.
- A volume of 100 μl of SUB (substrate) should be added to each well.
- Incubation should be performed for 10-20 min at room temperature (18-26C) in the dark (the intensity of the color change is temperature sensitive. We recommend observing the procedure of the color change and stopping the reaction upon good differentiation).
- A volume of 100 μl of STOP (stop solution) should be added to each well and mixed thoroughly.
- The absorption should be determined immediately using an ELISA reader at 450 nm. If the highest extinction of the standards (STD) is above the range of the photometer, absorption must be measured immediately at 405 nm and the results obtained should be used for evaluation. If possible, the extinctions from each measurement should be compared with extinctions obtained at a reference wavelength, for example 595, 620, 630, 650 nm, and 690 can be used.
| Results|| |
The four-parameter algorithm was used. It is recommended to use a linear ordinate for optical density and a logarithmic abscissa for concentration. When using a logarithmic abscissa, the zero calibrator must be specified with a value less than 1 (e.g. 0.001).
To obtain the calprotectin concentration in the stool samples, the result obtained should be multiplied by 2500 (dilution step IΧdilution step II).
Stool samples with calprotectin levels greater than the highest standard value should be diluted with sample dilution buffer and reassayed.
Control samples should be analyzed with each run. Results, generated from the analysis of control samples, should be evaluated for acceptability using appropriate statistical methods. The results for the patient samples may not be valid if, within the same assay, one or more values of the quality control sample are beyond the acceptable limits.
Samples yielding values above 50 mg/kg are considered as positive.
| Results|| |
- There was a highly significant increase in the mean value of total leukocyte count (TLC), platelets (PLT) count, ESR, and CRP, with a highly significant decrease in the mean value of hemoglobin in GIa (active UC) in comparison with the other groups as shown in [Table 1].
- There was a highly significant increase in the mean value of FC in active UC (GIa) patients in comparison with the inactive UC (GIb) patients and controls (GII). There was also a highly significant increase in the mean value of FC in the inactive UC (GIa) patients in comparison with the controls (GII) as shown in [Table 2].
- At the cut-off value of 131 μg/g, FC has 100% accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in differentiating UC patients from other patients with lower GI symptoms as shown in [Table 3] and [Figure 1].
- At the cut-off value of 253 μg/g, FC has 95% accuracy, sensitivity, specificity, PPV, and NPV in differentiating active from inactive UC patients as shown in [Table 4] and [Figure 2].
- There was a highly significant positive correlation between FC and ulcerative colitis activity index (UCAI), CRP, ESR, TLC, and PLT count as shown in [Table 5].
|Table 3: Diagnostic validity of fecal calprotectin in differentiating UC patients from other patients with lower GI symptoms|
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|Table 4: Diagnostic validity of fecal calprotectin in differentiating active and inactive UC patients|
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|Table 5: Correlation between fecal calprotectin level and UCAI, TLC, PLT count, ESR, and CRP|
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| Discussion|| |
In the present study, there was a highly significant increase in the mean value of TLC and PLT count in GIa (active UC) in comparison with the other groups. This was in agreement with Tibble et al. , who found higher TLC and PLT counts in active IBD patients in comparison with patients with quiescent disease, IBS patients, and controls, whereas no significant difference was found on comparing the results of patients with quiescent disease, IBS patients, and controls.
Several studies have reported the same results as in the study carried out by Öztürk et al. , who investigated whether platelet indices could be new biomarkers for IBDs; they reported that there was a statistically significant increase in platelet count in patients with active UC and CD than the other groups and concluded that platelet indices can be added to other inflammatory markers especially to monitor disease from the active phase to the remission phase. Also, Kayahan et al.  investigated whether reticulated PLT would be useful markers in the evaluation of UC activity and found that the mean platelet count was increased in patients with active compared with inactive UC or healthy donors. Moreover, Kapsoritakis et al.  reported that the mean platelet count was increased in patients with active compared with inactive UC, and in patients with active compared with inactive CD or healthy controls on investigating whether the mean platelet volume would be a useful marker in the evaluation of IBD activity.
The increase in TLC and PLT count could be attributed to the fact that these parameters are increased in inflammatory conditions as acute-phase reactants play an important role in inflammation. Besides their functions in the hemostatic process and in thrombus formation after an endothelial injury, blood PLT also play a role in the processes of inflammation and tissue repair that follows. For this purpose, they collaborate closely with all types of leukocytes. Activated PLT secrete chemotactic substances; they facilitate the binding of leukocytes to the endothelium and their subsequent extravasation, and they may influence the inflammatory responses of leukocytes in both stimulating and inhibiting ways. However, PLT themselves also contain an array of potent proinflammatory substances, and therefore they are considered as mediator and effector cells in inflammation .
In the current study, it was found that there was a highly significant increase in the mean value of ESR and CRP in GIa (active UC) in comparison with the other groups. Elevated ESR and CRP values in patients with active IBD have been reported by several studies ,. Moreover, Canani et al. (16)and Langhorst et al. (17) reported high specificity, both for CRP and ESR, although with a markedly lower sensitivity than fecal markers in the diagnosis of disease activity in IBD.
The presence of active gut inflammation in patients with IBD is associated with an acute-phase reaction and migration of leukocytes to the gut, and this is translated into the production of several proteins, which may be detected in serum or stools. On resolution of the event that triggered the production of these proteins, their concentrations will revert to normal levels but not all at the same speed. CRP has a short half-life (19 h) compared with other acute-phase proteins and will therefore increase early after the onset of inflammation and decrease rapidly after resolution of the inflammation .
The ESR is an indirect measurement of plasma acute-phase protein concentration and is influenced by the morphology of erythrocytes as well as plasma constituents such as immunoglobulins. As the concentrations of many serum proteins vary in patients with IBD and as some have long half-lives, the ESR is not rapidly responsive to changes in clinical status (the ESR may take several days to decrease even when rapid clinical improvement occurs). Hence, the ESR is a crude assessment of disease activity. In UC, where clinical, endoscopic, and histological activity is used to assess the overall disease, the correlation between ESR and disease activity is good. However, it may be normal in proctitis and proctosigmoiditis .
In the present study, there was a highly significant increase in the mean value of FC in active UC (GIa) patients in comparison with the inactive UC (GIb) patients and controls (GII). Also, there was a highly significant increase in the mean value of FC in the inactive UC (GIa) patients in comparison with the controls (GII). At the cut-off value of 131 μg/g, FC has 100% accuracy, sensitivity, specificity, PPV, and NPV in differentiating UC patients from other patients with lower GI symptoms. At the cut-off value of 253 μg/g, FC has 95% accuracy, sensitivity, specificity, PPV, and NPV in differentiating active from inactive UC patients.
FC has been studied in various GI disorders including IBD. Summerton and colleagues studied 116 patients for planned endoscopy. The group included 43 patients with upper-GI lesions, seven patients with IBD, seven patients with IBS, 31 patients with colonic disorders, and 28 healthy individuals. They found that upper-GI disorders showed little difference in calprotectin levels, Barrett's esophagus (median 6.8 mg/l), gastric ulcer (median 6.5 mg/l), or gastritis/duodenitis (median 5.2 mg/l), but these levels were all higher than the median calprotectin level of healthy individuals (4.5 mg/l). The esophageal and gastric carcinoma median value was elevated significantly at 30 mg/l. IBD was also associated with marked elevation (CD, 31.2 mg/l; UC, 116.2 mg/l). Colorectal polyps (median 3.7 mg/l) and adenoma (median 3.8 mg/l) showed no elevated levels in contrast to colorectal carcinoma (median 53.4 mg/l). The elevated calprotectin in IBD and colorectal carcinoma yielded a sensitivity of 81.8% and a specificity of 73.2%. The authors concluded that calprotectin levels are elevated in inflammation and cancer but are not useful in differentiating between these disorders. Calprotectin was not elevated in colonic polyps or adenomata. Thus, it can be useful as a screening method in a general gastroenterology population for IBD and those with carcinoma, as well as for the assessment and monitoring of disease activity in IBD .
Also, Tibble and colleagues measured the FC values of 602 patients with symptoms suggestive of IBS or organic intestinal disease. Patients with nonorganic disease, mainly IBS, had lower FC than patients with organic disease. The sensitivity and specificity of FC in identifying organic disease was 89 and 79%, respectively . Also, Erbayrak et al.  studied the role of FC in investigating IBD and found that FC was strongly associated with colorectal inflammation, indicating organic disease. Moreover, Langhorst and colleagues assessed fecal levels of calprotectin in 139 (54 IBS, 42 UC, 43 CD) patients undergoing diagnostic ileocolonoscopy. Calprotectin had a high sensitivity and specificity in identifying IBD (81.7 and 83.5%, respectively), with a slightly superior diagnostic accuracy for CD (81.4%) compared with UC (78.6%) .
In a more recent study, Manzand colleagues, studied the value of FC in the evaluation of patients with abdominal discomfort. The median calprotectin levels were higher in patients with significant findings (median 97 μg/g) than in patients without (10 μg/g). The area under the receiver operating characteristics curve to identify a significant finding was 0.877. Using 50 μg/g as a cut-off yielded a sensitivity of 73% and a specificity of 93% with good positive and negative likelihood ratios (10.8 and 0.29, respectively). They concluded that in patients with abdominal discomfort, FC is a useful noninvasive marker to identify clinically significant findings of the GI tract .
In another study, Henderson and colleagues showed that FC is a highly useful biomarker and performs better than all commonly used blood parameters during the initial investigation of suspected pediatric IBD. An FC level between 200 and 300 μg/g (sensitivity 89-93%, specificity 74-83%) yielded an optimum sensitivity of 89-93% and specificity of 74-83% .
In a meta-analysis, Von Roon and colleagues summarized data from 30 studies that included 5983 patients. FC was higher in IBD patients than in non-IBD patients (by 219 μg/g) and showed excellent pooled sensitivity and specificity rates in distinguishing between these groups (95 and 91%, respectively) . Most of these studies compared IBD patients with either IBS patients or healthy volunteers, that is the extremes of the clinical spectrum. This could overestimate the diagnostic accuracy of the test and impair its usefulness in clinical practice .
In another meta-analysis, Van Rheenen and colleagues compared the diagnostic accuracy of FC in the evaluation of patients with suspected IBD. Thirteen studies summarizing data of 1041 patients (670 adults, 371 children) were included. Studies were selected for their methodological robustness and had to present a paired design where FC values were measured before endoscopy. Pooled sensitivity and specificity rates of calprotectin testing were 93 and 96%, respectively. The specificity in children and teenagers was significantly lower (76%). In adults, using FC as a diagnostic test in suspected IBD for deciding upon endoscopy would result in a 67% reduction in patients requiring endoscopy, but would also result in a delayed diagnosis for 6% of patients because of false-negative test results .
Van Rheenen et al.  reported that a considerable proportion of the patients with a false-positive FC test result were found to have an organic GI condition other than IBD for which endoscopy is inevitable, whereas a false-negative FC test result would lead to continuation of symptoms, delay in diagnosis, and failure to introduce effective treatment in a timely manner. In another study, Carroccio and colleagues investigated 120 patients with chronic diarrhea. FC identified organic causes of diarrhea with a 64% sensitivity and an 80% specificity. False-positive results were associated with the use of aspirin or NSAIDs whereas false-negative results were mainly found in patients with celiac disease .
Loitsch and colleagues performed a comparative evaluation of FC and S100A12 as noninvasive markers for disease activity in IBD. They found that the higher cut-offs for both markers improved diagnostic accuracy for discriminating active from inactive IBD .
In the current study, there was a highly significant positive correlation between FC and UCAI, ESR, CRP, TLC, and PLT count. This was in agreement with Schoepfer and colleagues who evaluated the correlation between endoscopic activity and FC, CRP, PLT, TLC, and the clinical score (Lichtiger Index). They found that endoscopic disease activity correlated best with FC, followed by the Lichtiger Index, CRP, TLC, and PLT count. FC was the only marker that could discriminate between different grades of endoscopic activity. FC with a cut-off of 57 μg/g had a sensitivity of 91% and a specificity of 90% to detect endoscopically active disease .
Similarly, Kolho and Turner carried out a retrospective study that included all children with UC in whom calprotectin was measured and clinical data were recorded for the assessment of the PUCAI. They found a good correlation between the PUCAI and FC. In clinically severe disease (PUCAI>65), calprotectin was very high (>1000 μg/g) in all cases and did not provide any additional information for clinical assessment. It is noteworthy that the PUCAI is much more responsive to a rapid change than calprotectin in severe disease, that is, the PUCAI shows a sharp decrease within only a few days of starting effective medication, reflecting the well-known notion that mucosal healing lags after clinical remission. However, some of those in clinical remission according to PUCAI still had elevated calprotectin levels, but in the majority, the levels were only moderately elevated .
Also, Rodrνguez-Moranta and colleagues found that FC shows a better correlation with the degree of inflammation than clinical indicators and serological markers. In addition, it could also be useful to predict mucosal cure and the risk of recurrence . Schoepfer and colleagues reported similar results in patients with IBD; endoscopic disease activity correlated best with FC (R = 0.834), followed by the Clinical Activity Index (R = 0.672), CRP (R=0.503), and blood leukocytes (R = 0.461). The overall accuracy of calprotectin in detecting endoscopically active disease was 89% and it was the only marker to discriminate inactive, mild, moderate, and highly active disease . Lobatσn and colleagues evaluated the ability of FC to predict endoscopic activity according to the Mayo score in 123 patients with UC. They found that FC was an accurate marker of endoscopic remission in UC .
In general, FC values correlate better with endoscopic findings than with clinical activity. Accordingly, this sensitive marker may detect residual inflammatory activity in patients with presumably quiescent disease . This is also in agreement with Ricanek et al.  who reported that FC levels correlated highly with endoscopic activity scores in patients with suspected IBD, but correlated inconsistently with clinical activity scores.
In a study on pediatric IBD, Fagerberg and colleagues studied 39 children with IBD. The concentrations of FC were correlated to macroscopic and microscopic assessments of the extent and severity of inflammation in eight colonic segments for each patient. They found that FC correlated significantly to the extent and severity of macroscopic and microscopic findings of colonic inflammation. The median FC was 392 μg/g in children with clinical IBD symptoms and 32.9 μg/g in asymptomatic IBD patients. Of the asymptomatic children, 56% achieved complete microscopic mucosal healing, and their median FC was 9.9 μg/g. They concluded that FC can be used as a marker for estimation of colonic inflammation in pediatric IBD .
Lasson and colleagues evaluated the prognostic role of FC 3 months after the initial therapy. They found that levels of FC 3 months after the initial therapy in patients with new onset of UC predicted the disease course over the following years, and they may be valuable in the clinical management of these patients . Also, Smith and Gaya  studied the utility of FC analysis in adult IBD and they found that FC correlates well with mucosal disease activity and this in turn makes it useful for assessment of activity, monitoring response to treatment, and predicting relapse.
Measurement of FC is highly useful for the diagnosis and disease monitoring of patients with IBD, and might additionally predict disease outcome. Future studies should evaluate the usefulness of FC testing to guide treatment decisions and to assess their effect on long-term outcomes .
| Conclusion|| |
- FC is a valuable, simple, easily performed, and cost-effective noninvasive marker in evaluating patients with UC.
- FC differentiated UC and other diseases causing colonic symptoms (cut-off value of 131 μg/g) and between active and inactive UC (cut-off value of 235 μg/g) with high accuracy, sensitivity, and specificity.
- FC levels correlate well with other markers for UC activity (UCAI, ESR, CRP, TLC, and PLT count) and could be a reliable surrogate marker for the severity of UC.
- Serial measurement of FC could be recommended for patients with UC to assess disease severity, response to treatment, induction and maintenance of remission, and recurrence of activity.
- Measurement of FC level could be recommended as a screening tool for patients with lower GI symptoms and when elevated, early endoscopic assessment is recommended to rule out IBD and other organic diseases.
- Further studies on a large number of patients are needed to determine the role of FC in the diagnosis of other organic colonic diseases in general and colonic malignancy in particular.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]