Fecal calprotectin distinguishes between organic disease and functional disorder

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Fecal calprotectin is a non-invasive test that helps clinicians distinguish between organic inflammatory bowel disease (IBD) and functional disorder (irritable bowel syndrome, or IBS), according to new research from the UK.

Fecal calprotectin (FC) is a cytosolic protein released by neutrophils in response to inflammation.

It has 87% negative predictive value to exclude IBD, and cutoffs less than 250 micrograms/gram had 90% sensitivity to determine remission in IBD. Once frozen, FC is stable, and the ELISA monoclonal plates were broadly comparable, the authors reported online March 17 in Frontline Gastroenterology.

"This is a large study that closely correlates endoscopic mucosal evaluation and fecal calprotectin, with calprotectin measured within 1 month of endoscopic examination," said senior author Dr. Ramesh P. Arasaradnam, from the Clinical Sciences Research Institute and University Hospitals Coventry and Warwickshire in Coventry, UK, in an email to Reuters Health.

"This biomarker can quite effectively be used to distinguish IBS from IBD," he said.

Dr. Arasaradnam and colleagues tested 311 patients with altered bowel habit for FC. Of these, 144 had IBS, 148 had IBD, and 19 had other organic causes.

The researchers also compared FC readings obtained from the Buhlmann and the PhiCal v2 (which has superseded no-longer-available PhiCal v1) proprietary enzyme-linked immunosorbent assay (ELISA) kits.

They found that, to distinguish between IBS and IBD, a FC cutoff of 50 mcg/g returned a sensitivity and specificity of 88% and 78%, respectively, with a positive predictive value of 79% and a negative predictive value of 87%. The area under the receiver operating curve (AUROC) was 0.84.

However, using a cutoff of 100 mcg/g, sensitivity increased to 97% with a fall in specificity to 76% and a positive predictive value of 75%, a negative predictive value of 97%, and an AUROC of 0.88.

For patients with IBD, FC values below 250 mcg/g were associated with disease remission, with sensitivity and specificity of 90% and 76%, respectively, and an AUROC of 0.93. Remission was confirmed by finding quiescent disease on endoscopy and no active inflammation on histology.

FC levels fell significantly when stored at room temperature compared with storage at 4 degrees C, especially levels of FC <100 mcg/g. If frozen at 20 degrees C, FC remained stable even prior to extraction into buffer solution, for at least six weeks. Once extracted into buffer solution, though, it remained stable at 20 degrees C for up to 2.5 months.

The Buhlmann and the PhiCal v2 test results correlated well, with r2=0.95 for FC samples >250 mcg/g and r2=0.72 for FC samples <250 mcg/g.

Dr. Julie Bass, of the University of Missouri-Kansas City School of Medicine and the Inflammatory Bowel Disease Program at Children's Mercy Hospital in Kansas City, told Reuters Health in an email, "The given cutoff values are helpful in determining which patients need further workup for possible IBD. In those with known IBD, they are helpful in determining if symptoms are concerning for active disease versus being suggestive of functional symptoms, which may exist in an IBD patient in remission."

"Fecal calprotectin, in conjunction with other clinical parameters, allows clinicians to limit unnecessary invasive testing in select patients," Dr. Bass added. She was not involved in the study.

"The study population was carefully chosen to allow us to validate symptoms and assess all subjects with endoscopy," the authors wrote. "Further studies are now needed to assess the use in a primary care population."

SOURCE: http://bit.ly/RlDC4p

Frontline Gastroenterol 2014.

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