Skip to main content

Utility of fecal calprotectin as a discriminative biomarker between ulcerative colitis and irritable bowel syndrome and its ability to be used for the assessment of the remission stage of ulcerative colitis

Abstract

Background and aim

Fecal calprotectin (FC) has been proposed in recent studies as a sensitive, specific biomarker for the diagnosis of ulcerative colitis (UC). Hence, the present study sought to investigate the efficacy of FC for the diagnosis and monitoring of UC, as well as to assess the correlation of FC with other disease activity indexes.

Research design and methods

The present study included 96 consecutive patients who presented with lower gastrointestinal complaints. Patients were classified into two groups: group I (which included patients with UC) and group II (which included patients with irritable bowel syndrome); then, according to the disease activity, group I was subdivided into the following: group Ia (which included patients with active UC) and group Ib (which included only those patients of group Ia who were in the remission stage of UC). For all patients, erythrocyte sedimentation rate and C-reactive protein were determined; moreover, all patients underwent quantitative determination of calprotectin in stool samples, abdominal ultrasonography, and complete colonoscopy with biopsies for the histopathological examination to assess the disease severity by using the UC activity index according to the Mayo endoscopic and Geboes histological scores. The diagnostic validity of FC levels in correlation with Mayo Disease Activity Index (MDAI) was then investigated.

Results

FC levels showed highly significant increase in patients with active UC compared with inactive UC and irritable bowel syndrome (524.17 ± 48.0 vs. 184.48 ± 3.33 and 47.17 ± 5.32 mg/kg, respectively, P < 0.001). FC level has 100% accuracy, sensitivity, specificity, positive predictive value, and negative predictive value in distinguishing UC patients from the control group at a cutoff value of 140 mg/kg, but at a cutoff value of 223 mg/kg FC level shows 93.4% accuracy, 89.8% sensitivity, 97% specificity, 97.4% positive predictive value, and 55% negative predictive value to distinguish the active phase from the remission phase of UC. In addition, there was a statistically significant proportional correlation between FC and the MDAI, but the correlation between FC and histological inflammatory activity statistically was more significant than with MDAI (r = 0.75, P < 0.001).

Conclusion

FC level is an accurate, noninvasive biomarker in clinical practice with high specificity and sensitivity for the diagnosis and monitoring of UC, as well as good marker for the evaluation of disease activity. Therefore, it can be used as a monitoring test to assess medical response and to predict clinical relapse of the disease.

References

  1. Watanabe T, Aoyagi K, Nimura S, Eguchi K, Tomioka Y, Sakisaka S. New fecal biomarker, α1-acid glycoprotein, for evaluation of inflammatory bowel disease: comparison with calprotectin and lactoferrin. Med Bull Fukuoka Univ 2013; 40: 155–162.

    Google Scholar 

  2. Mao R, Xiao YL, Gao X, Chen BL, He Y, Yang L, et al. Fecal calprotectin in predicting relapse of inflammatory bowel diseases: a meta-analysis of prospective studies. Inflamm Bowel Dis 2012; 18: 1894–1899.

    Article  Google Scholar 

  3. Reinisch W, Sandborn WJ, Hommes DW, D’Haens G, Hanauer S, Schreiber S, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut 2011; 60: 780–787.

    Article  CAS  Google Scholar 

  4. Vermeire S, Van Assche G, Rutgeerts P. Laboratory markers in IBD: useful, magic, or unnecessary toys? Gut 2006; 55: 426–431.

    Article  CAS  Google Scholar 

  5. Sipponen T, Savilahti E, Kolho KL, Nuutinen H, Turunen U, Färkkilä M. Crohn’s disease activity assessed by fecal calprotectin and lactoferrin: correlation with Crohn’s disease activity index and endoscopic findings. Inflamm Bowel Dis 2008; 14: 40–46.

    Article  Google Scholar 

  6. Desai D, Faubion WA, Sandborn WJ. Review article: biological activity markers in inflammatory bowel disease. Aliment Pharmacol Ther 2007; 25: 247–255.

    Article  CAS  Google Scholar 

  7. Tibble JA, Sigthorsson G, Bridger S, Fagerhol MK, Bjarnason I. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 2000; 119: 15–22.

    Article  CAS  Google Scholar 

  8. Mehrjardi A, Saber-Afsharian M, Mirskandari M, Ebrahimi-Daryani N, Faghihi A, Iranikhah T. Comparison of fecal calprotectin level in inflammatory bowel disease and irritable bowel syndrome. Govaresh 2010; 14: 275–278.

    Google Scholar 

  9. 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.

    Article  Google Scholar 

  10. Dhaliwal A, Zeino Z, Tomkins C, Cheung M, Nwokolo C, Smith S, et al. Utility of faecal calprotectin in inflammatory bowel disease (IBD): what cutoffs should we apply? Frontline Gastroenterol 2015; 6: 14–19.

    Article  CAS  Google Scholar 

  11. Yang Z, Clark N, Park KT. Effectiveness and cost-effectiveness of measuring fecal calprotectin in diagnosis of inflammatory bowel disease in adults and children. Clin Gastroenterol Hepatol 2014;12: 253.e2–262.e2.

    Article  Google Scholar 

  12. Travis SP, Higgins PD, Orchard T, Van Der Woude CJ, Panaccione R, Bitton A, et al. Review article: defining remission in ulcerative colitis. Aliment Pharmacol Ther 2011; 34: 113–124.

    Article  CAS  Google Scholar 

  13. Shih DQ, Kwan LY. All roads lead to Rome: update on Rome III criteria and new treatment options. 2007 Gastroenterol Rep; 1: 56–65.

  14. Rosenberg L, Nanda KS, Zenlea T, Gifford A, Lawlor GO, Falchuk KR, et al. Histologic markers of inflammation in patients with ulcerative colitis in clinical remission. Clin Gastroenterol Hepatol. 2013; 11: 991–996.

    Article  Google Scholar 

  15. Douglas K, RexandYang Z. Fecal calprotectin is cost-effective for IBD screening. Clin Gastroenterol Hepatol 2014; 4: 67–78.

    Google Scholar 

  16. Joshi S, Lewis SJ, Creanor S, Ayling RM. Age-related faecal calprotectin, lactoferrin and tumour M2-PK concentrations in healthy volunteers. Ann Clin Biochem. 2010; 47 (Pt 3): 259–263.

    Article  CAS  Google Scholar 

  17. Røseth AG, Aadland E, Jahnsen J, Raknerud N. Assessment of disease activity in ulcerative colitis by faecal calprotectin, a novel granulocyte marker protein. Digestion 1997; 58: 176–180.

    Article  Google Scholar 

  18. Lehmann FS, Burri E, Beglinger C. The role and utility of faecal markers in inflammatory bowel disease. Therap Adv Gastroenterol 2015; 8: 23–36.

    Article  Google Scholar 

  19. Theede K, Holck S, Ibsen P, Ladelund S, Nordgaard-Lassen I, Nielsen AM. Level of fecal calprotectin correlates with endoscopic and histologic inflammation and identifies patients with mucosal healing in ulcerative colitis. Clin Gastroenterol Hepatol 2015: 13: 1929.e1–1936.e1.

  20. Xiang JY, Ouyang Q, Li GD, Xiao NP. Clinical value of fecal calprotectin in determining disease activity of ulcerative colitis. World J Gastroenterol 2008; 14: 53–57.

    Article  CAS  Google Scholar 

  21. Kotze LM, Nisihara RM, Marion SB, Cavassani MF, Kotze PG. Fecal calprotectin: levels for the ethiological diagnosis in Brazilian patients with gastrointestinal symptoms. Arq Gastroenterol 2015; 52: 50–54.

    Article  Google Scholar 

  22. Nouh MAE, Ali AAE, El Halim EFA, Mohamed HI, El Ghany AMA, Badawy AM. Calprotectin as a fecal marker for diagnosis and follow-up in patients with ulcerative colitis. Menoufia Med J 2014; 27: 35–43.

    Article  Google Scholar 

  23. Vieira A, Fang CB, Rolim EG, Klug WA, Steinwurz F, Rossini LG, Candelária PA. Inflammatory bowel disease activity assessed by fecal calprotectin and lactoferrin: correlation with laboratory parameters, clinical, endoscopic and histological indexes. BMC Res Notes 2009; 2: 221.

    Article  Google Scholar 

  24. van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ 2010; 341: c3369.

    Article  Google Scholar 

  25. Kalantari H, Taheri A, Yaran M. Fecal calprotectin is a useful marker to diagnose ulcerative colitis from irritable bowel syndrome. Adv Biomed Res 2015; 4: 85.

    Article  Google Scholar 

  26. Røseth AG, Aadland E, Jahnsen J, Raknerud N. Assessment of disease activity in ulcerative colitis by faecal calprotectin, a novel granulocyte marker protein. Digestion 1997; 58: 176–180.

    Article  Google Scholar 

  27. Bunn SK, Bisset WM, Main MJ, Golden BE. Fecal calprotectin as a measure of disease activity in childhood inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2001; 32: 171–177.

    Article  CAS  Google Scholar 

  28. Schoepfer AM, Trummler M, Seeholzer P, Seibold-Schmid B, Seibold F. Discriminating IBD from IBS: comparison of the test performance of fecal markers, blood leukocytes, CRP, and IBD antibodies. Inflamm Bowel Dis 2008; 14: 32–39.

    Article  Google Scholar 

  29. Schroder O, Naumann M, Shastri Y, Povse N, Stein J. Prospective evaluation of faecal neutrophil-derived proteins in identifying intestinal inflammation: combination of parameters does not improve diagnostic accuracy of calprotectin. Aliment Pharmacol Ther 2007; 26: 1035–1042.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hossam M. Elsaadany MD.

Additional information

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Elsaadany, H.M., Almaghraby, M.F., Edrees, A.A. et al. Utility of fecal calprotectin as a discriminative biomarker between ulcerative colitis and irritable bowel syndrome and its ability to be used for the assessment of the remission stage of ulcerative colitis. Egypt J Intern Med 28, 21–27 (2016). https://doi.org/10.4103/1110-7782.182956

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.4103/1110-7782.182956

Keywords