Home Medicine Fecal leukocyte esterase levels predict endoscopic severity as an alternative biomarker in inflammatory bowel disease
Article
Licensed
Unlicensed Requires Authentication

Fecal leukocyte esterase levels predict endoscopic severity as an alternative biomarker in inflammatory bowel disease

  • Feng-Pai Tsai ORCID logo , Meng-Tzu Weng ORCID logo , Hsin-Yun Wu ORCID logo , Zhi-Che Chen ORCID logo , Chien-Chih Tung ORCID logo , Chun-Ying Wang ORCID logo and Shu-Chen Wei ORCID logo EMAIL logo
Published/Copyright: September 1, 2025
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 64 Issue 1

Abstract

Objectives

Our previous study revealed a correlation between fecal leukocyte esterase and fecal calprotectin levels. This study assessed the predictive value of fecal leukocyte esterase compared with fecal calprotectin and C-reactive protein of inflammatory bowel disease.

Methods

Patients with inflammatory bowel disease who underwent ileocolonoscopy at National Taiwan University Hospital from March 2022 to March 2024 were included. Fecal leukocyte esterase and fecal calprotectin levels from stool samples collected within one month of endoscopy were analyzed. Active ulcerative colitis and Crohn’s disease were defined as Mayo endoscopic score ≥2 or simple endoscopic score for Crohn’s disease ≥7, respectively. Sensitivity, specificity, predictive values, and areas under the receiver operating characteristic curve were calculated using IBM SPSS Statistics 29.

Results

Of the 203 patients (100 with ulcerative colitis and 103 with Crohn’s disease), fecal leukocyte esterase levels were significantly correlated with fecal calprotectin levels (r=0.425, p<0.001) and endoscopic severity in ulcerative colitis (r=0.432, p<0.001) and Crohn’s disease (r=0.311, p=0.001). For predicting Mayo endoscopic scores ≥2 in ulcerative colitis using fecal leukocyte esterase, fecal calprotectin, and C-reactive protein, areas under the curve were 0.731, 0.785, and 0.558, respectively. For predicting simple endoscopic scores for Crohn’s disease ≥7, areas under the curve were 0.706, 0.800, and 0.770, respectively. No significant difference was observed between fecal leukocyte esterase and fecal calprotectin.

Conclusions

Fecal leukocyte esterase correlates with fecal calprotectin and predicts endoscopic severity in inflammatory bowel disease.

Keywords: disease monitoring; noninvasive; point-of-care testing; treat-to-target
Corresponding author: Shu-Chen Wei, MD, PhD, Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei, Taiwan, E-mail:

Funding source: Ministry of Science and Technology, Taiwan

Award Identifier / Grant number: 111-2314-B-002-188-MY3

Funding source: The Liver Disease Prevention and Treatment Research Foundation, Taiwan

Funding source: National Taiwan University Hospital

Award Identifier / Grant number: NTUH MS-507

Acknowledgments

We thank the staff of the Second Core Lab, Department of Medical Research, National Taiwan University Hospital for technical support during the study. We thank the staff of Department of Medical Research, National Taiwan University Hospital Hsin-Chu Branch for their assistance with the statistical analysis. This manuscript was edited by Wallace Academic Editing.

  1. Research ethics: This study was approved by the Institutional Review Board of National Taiwan University Hospital (IRB number: 202112116RINC). All protocols conformed to the ethical principles for medical research involving human patients outlined in the Declaration of Helsinki, which was updated in 2013.

  2. Informed consent: All the patients gave their written informed consent.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. Conceptualization: FPT, MTW, SCW; Methodology: MTW, CYW, SCW; Investigation: FPT, MTW, HYW, ZCC, CCT, SCW; Data analysis: MTW, CYW; Data interpretation: All authors; Writing – original draft: FPT, MTW; Writing – review and editing: All authors; Approval: All authors.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: This work was supported by the grants from the Ministry of Science and Technology, Taiwan (111-2314-B-002-188-MY3 to SCW), National Taiwan University Hospital (NTUH MS-507 to SCW), and The Liver Disease Prevention and Treatment Research Foundation, Taiwan (to SCW and MTW).

  7. Data availability: The datasets analyzed during the current study are not publicly available due to privacy and ethical concerns but are available from the corresponding author on reasonable request.

References

1. Hazel, K, O’Connor, A. Emerging treatments for inflammatory bowel disease. Therapeut Adv Chron Dis 2020;11:2040622319899297. https://doi.org/10.1177/2040622319899297.Search in Google Scholar PubMed PubMed Central

2. Neurath, MF, Travis, SP. Mucosal healing in inflammatory bowel diseases: a systematic review. Gut 2012;61:1619–35. https://doi.org/10.1136/gutjnl-2012-302830.Search in Google Scholar PubMed

3. Turner, D, Ricciuto, A, Lewis, A, D’Amico, F, Dhaliwal, J, Griffiths, AM, et al.. STRIDE-II: an update on the selecting therapeutic targets in inflammatory bowel disease (STRIDE) initiative of the international organization for the study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology 2021;160:1570–83. https://doi.org/10.1053/j.gastro.2020.12.031.Search in Google Scholar PubMed

4. Gracie, DJ, Williams, CJ, Sood, R, Mumtaz, S, Bholah, MH, Hamlin, PJ, et al.. Poor correlation between clinical disease activity and mucosal inflammation, and the role of psychological comorbidity, in inflammatory bowel disease. Am J Gastroenterol 2016;111:541–51. https://doi.org/10.1038/ajg.2016.59.Search in Google Scholar PubMed

5. Wei, SC, Tung, CC, Weng, MT, Wong, JM. Experience of patients with inflammatory bowel disease in using a home fecal calprotectin test as an objective reported outcome for self-monitoring. Intestinal Res 2018;16:546–53. https://doi.org/10.5217/ir.2018.00052.Search in Google Scholar PubMed PubMed Central

6. Mosli, MH, Zou, G, Garg, SK, Feagan, SG, MacDonald, JK, Chande, N, et al.. C-Reactive protein, fecal calprotectin, and stool lactoferrin for detection of endoscopic activity in symptomatic inflammatory bowel disease patients: a systematic review and meta-analysis. Am J Gastroenterol 2015;110:802–19; quiz 20. https://doi.org/10.1038/ajg.2015.120.Search in Google Scholar PubMed

7. Wright, EK, Kamm, MA, De Cruz, P, Hamilton, AL, Ritchie, KJ, Krejany, EO, et al.. Measurement of fecal calprotectin improves monitoring and detection of recurrence of Crohn’s disease after surgery. Gastroenterology 2015;148:938–47 e1. https://doi.org/10.1053/j.gastro.2015.01.026.Search in Google Scholar PubMed

8. Plevris, N, Fulforth, J, Lyons, M, Siakavellas, SI, Jenkinson, PW, Chuah, CS, et al.. Normalization of fecal calprotectin within 12 months of diagnosis is associated with reduced risk of disease progression in patients with Crohn’s disease. Clin Gastroenterol Hepatol: Off Clin Pract J Am Gastroenterol Assoc 2021;19:1835–44.e6. https://doi.org/10.1016/j.cgh.2020.08.022.Search in Google Scholar PubMed

9. Sollelis, E, Quinard, RM, Bouguen, G, Goutte, M, Goutorbe, F, Bouvier, D, et al.. Combined evaluation of biomarkers as predictor of maintained remission in Crohn’s disease. World J Gastroenterol 2019;25:2354–64. https://doi.org/10.3748/wjg.v25.i19.2354.Search in Google Scholar PubMed PubMed Central

10. Guidi, L, Marzo, M, Andrisani, G, Felice, C, Pugliese, D, Mocci, G, et al.. Faecal calprotectin assay after induction with anti-Tumour necrosis factor α agents in inflammatory bowel disease: prediction of clinical response and mucosal healing at one year. Dig Liver Dis: Off J Ital Soc Gastroenterol Ital Assoc Stud Liver 2014;46:974–9. https://doi.org/10.1016/j.dld.2014.07.013.Search in Google Scholar PubMed

11. Tsai, FP, Weng, MT, Chang, CH, Zeng, MH, Wei, SC. A simplified fecal leukocyte esterase strip test results as a low cost, widely available, alternative bowel inflammation biomarker. J Formos Med Assoc=Taiwan yi zhi 2024;123:1099–103. https://doi.org/10.1016/j.jfma.2024.01.025.Search in Google Scholar PubMed

12. Khakoo, NS, Lewis, A, Roldan, GA, Al Khoury, A, Quintero, MA, Deshpande, AR, et al.. Patient adherence to fecal calprotectin testing is low compared to other commonly ordered tests in patients with inflammatory bowel disease. Crohn’s colitis 360 2021;3:otab028. https://doi.org/10.1093/crocol/otab028.Search in Google Scholar PubMed PubMed Central

13. Kalla, R, Boyapati, R, Vatn, S, Hijos, G, Crooks, B, Moore, GT, et al.. Patients’ perceptions of faecal calprotectin testing in inflammatory bowel disease: results from a prospective multicentre patient-based survey. Scand J Gastroenterol 2018;53:1437–42. https://doi.org/10.1080/00365521.2018.1527394.Search in Google Scholar PubMed

14. European Confederation of Laboratory M. European urinalysis guidelines. Scand J Clin Lab Invest Suppl 2000;231:1–86.Search in Google Scholar

15. Dumoulin, EN, Van Biervliet, S, De Vos, M, Himpe, J, Speeckaert, MM, Delanghe, JR, et al.. Faecal leukocyte esterase activity is an alternative biomarker in inflammatory bowel disease. Clin Chem Lab Med 2015;53:2003–8. https://doi.org/10.1515/cclm-2015-0040.Search in Google Scholar PubMed

16. Trasolini, R, Zhu, K, Klemm, N, Park, S, Salh, B. Fecal leukocyte esterase, an alternative biomarker to fecal calprotectin in inflammatory bowel disease: a pilot series. Gastro Hep Adv 2022;1:45–51. https://doi.org/10.1016/j.gastha.2021.10.006.Search in Google Scholar PubMed PubMed Central

17. Phadia™ 250 – product information sheet. https://www.thermofisher.com/content/dam/diagnostics/commercial/phadia/TF_Phadia-250-ProductInformationSheet_Review.pdf.Search in Google Scholar

18. Abebayehu, A. Urine test strip analysis, concentration range and its interpretations of the parameters. GSC Biol Pharm Sci 2023;22:1–13.10.30574/gscbps.2023.22.2.0091Search in Google Scholar

19. Schroeder, KW, Tremaine, WJ, Ilstrup, DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 1987;317:1625–9. https://doi.org/10.1056/nejm198712243172603.Search in Google Scholar PubMed

20. Daperno, M, D’Haens, G, Van Assche, G, Baert, F, Bulois, P, Maunoury, V, et al.. Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc 2004;60:505–12. https://doi.org/10.1016/s0016-5107(04)01878-4.Search in Google Scholar PubMed

21. Oord, T, Hornung, N. Fecal calprotectin in healthy children. Scand J Clin Lab Investig 2014;74:254–8. https://doi.org/10.3109/00365513.2013.879732.Search in Google Scholar PubMed

22. Silverberg, MS, Satsangi, J, Ahmad, T, Arnott, ID, Bernstein, CN, Brant, SR, et al.. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a working party of the 2005 Montreal world congress of gastroenterology. Can J Gastroenterol=J canadien de gastroenterologie 2005;19:5a–36a. https://doi.org/10.1155/2005/269076.Search in Google Scholar PubMed

23. Vázquez Morón, JM, Pallarés Manrique, H, Machancoses, FH, Ramos, LM, Ruiz Frutos, C. Accurate cut-offs for predicting endoscopic activity and mucosal healing in Crohn’s disease with fecal calprotectin. Rev Esp Enferm Dig 2017;109:130–6. https://doi.org/10.17235/reed.2017.4542/2016.Search in Google Scholar PubMed

24. Bodelier, AG, Jonkers, D, van den Heuvel, T, de Boer, E, Hameeteman, W, Masclee, AA, et al.. High percentage of IBD patients with indefinite fecal calprotectin levels: additional value of a combination score. Dig Dis Sci 2017;62:465–72. https://doi.org/10.1007/s10620-016-4397-6.Search in Google Scholar PubMed PubMed Central

25. Morris, MW, Stewart, SA, Heisler, C, Sandborn, WJ, Loftus, EV, Zello, GA, et al.. Biomarker-based models outperform patient-reported scores in predicting endoscopic inflammatory disease activity. Inflamm Bowel Dis 2018;24:277–85. https://doi.org/10.1093/ibd/izx018.Search in Google Scholar PubMed

26. Ungaro, RC, Yzet, C, Bossuyt, P, Baert, FJ, Vanasek, T, D’Haens, GR, et al.. Deep remission at 1 year prevents progression of early Crohn’s disease. Gastroenterology 2020;159:139–47. https://doi.org/10.1053/j.gastro.2020.03.039.Search in Google Scholar PubMed PubMed Central

27. Gecse, KB, Brandse, JF, van Wilpe, S, Löwenberg, M, Ponsioen, C, van den Brink, G, et al.. Impact of disease location on fecal calprotectin levels in Crohn’s disease. Scand J Gastroenterol 2015;50:841–7. https://doi.org/10.3109/00365521.2015.1008035.Search in Google Scholar PubMed

28. Dumoulin, EN, Van Biervliet, S, Langlois, MR, Delanghe, JR. Proteolysis is a confounding factor in the interpretation of faecal calprotectin. Clin Chem Lab Med 2015;53:65–71. https://doi.org/10.1515/cclm-2014-0568.Search in Google Scholar PubMed

29. Patel, HP. The abnormal urinalysis. Pediatr Clin 2006;53:325–37. https://doi.org/10.1016/j.pcl.2006.02.004.Search in Google Scholar PubMed

30. Bacârea, A, Fekete, GL, Grigorescu, BL, Bacârea, VC. Discrepancy in results between dipstick urinalysis and urine sediment microscopy. Exp Ther Med 2021;21:538. https://doi.org/10.3892/etm.2021.9971.Search in Google Scholar PubMed PubMed Central

31. Winkens, RA, Leffers, P, Degenaar, CP. Urine test strips: how reproducible are readings? Can Fam Physician Medecin de famille canadien 1992;38:1095–9.Search in Google Scholar

32. Tibble, JA, Sigthorsson, G, Foster, R, Scott, D, Fagerhol, MK, Roseth, A, et al.. High prevalence of NSAID enteropathy as shown by a simple faecal test. Gut 1999;45:362–6. https://doi.org/10.1136/gut.45.3.362.Search in Google Scholar PubMed PubMed Central

33. Kim, ES. Optimal cutoff level of fecal calprotectin for detecting small bowel inflammation in Crohn’s disease. Gut and liver 2021;15:637–8. https://doi.org/10.5009/gnl210393.Search in Google Scholar PubMed PubMed Central

Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0747).

Received: 2025-06-17
Accepted: 2025-08-18
Published Online: 2025-09-01
Published in Print: 2026-01-27

© 2025 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Keeping pace with patient safety by developing and qualifying higher-order reference measurement procedures for laboratory measurement standardization
  4. Review
  5. The role of AI in pre-analytical phase – use cases
  6. Opinion Paper
  7. Total laboratory automation: fit for its intended purposes?
  8. Guidelines and Recommendations
  9. EFLM checklist for the assessment of AI/ML studies in laboratory medicine: enhancing general medical AI frameworks for laboratory-specific applications
  10. Candidate Reference Measurement Procedures and Materials
  11. An isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedure for the quantification of cortisol in human serum and plasma
  12. Isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedures for the quantification of 24(R),25-dihydroxyvitamin D2 and 24(R),25-dihydroxyvitamin D3 in human serum and plasma
  13. An isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedure for the quantification of cortisone in human serum and plasma
  14. Candidate reference measurement procedure based on isotope dilution-two dimensional-liquid chromatography-tandem mass spectrometry for the quantification of androstenedione in human serum and plasma
  15. An isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedure for the quantification of 17β-estradiol in human serum and plasma
  16. Isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedures for the quantification of total and free phenytoin in human serum and plasma
  17. An isotope dilution-liquid chromatography-tandem mass spectrometry based candidate reference measurement procedure for the simultaneous quantification of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in human serum and plasma
  18. General Clinical Chemistry and Laboratory Medicine
  19. Quality assurance using patient split samples: recommendations for primary healthcare laboratories
  20. Age distorts the interpretation of FIB-4
  21. Not all anti-parietal cell antibody tests are equal for diagnosing pernicious anemia
  22. Impact of renal and hepatic function on dihydropyrimidine dehydrogenase phenotype assessed by enzyme activity in peripheral blood mononuclear cells and uracilemia
  23. Fecal leukocyte esterase levels predict endoscopic severity as an alternative biomarker in inflammatory bowel disease
  24. Cancer Diagnostics
  25. CA-125 glycovariant assays enhance diagnostic sensitivity in the detection of epithelial ovarian cancer
  26. Cardiovascular Diseases
  27. Defining the analytical characteristics of a novel high-sensitivity point-of-care troponin I assay in its intended clinical environment
  28. An automatic chemiluminescence immunoassay for a novel biomarker NT-IGFBP-4: analytical performance and clinical relevance in heart failure
  29. Analysis of total cholesterol results measured in the initial period of the Croatian screening program for familial hypercholesterolemia: a pilot study
  30. Diabetes
  31. Comparison of seven different enzymatic methods for serum glycated albumin in pregnant women: a multicenter study
  32. Infectious Diseases
  33. Comparative analysis of monocyte distribution width alterations in Escherichia coli sepsis: insights from in vivo and ex vivo models
  34. Proadrenomedullin for prediction of early and mid-term mortality in patients hospitalized for community-acquired pneumonia
  35. Annual Reviewer Acknowledgment
  36. Reviewer Acknowledgment
  37. Letters to the Editor
  38. Biological variation of serum Golgi protein 73 concentrations
  39. Are vitamins A and E results truly traceable and clinically useful? A practical and critical inquiry
  40. Tafasitamab interference in immunofixation electrophoresis
  41. Improvement in the turnaround time of PTH(1–84) as part of the intraoperative PTH monitoring for parathyroidectomy
  42. Rethinking the use of “one-way ANOVA” in CLSI EP15-A3 – a call for terminological precision and methodological clarity
  43. Toxic beauty: acute kidney injury triggered by hair-straightening treatment
  44. Congress Abstracts
  45. 57th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
https://doi.org/10.1515/cclm-2025-0747
Keywords for this article
disease monitoring; noninvasive; point-of-care testing; treat-to-target

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Keeping pace with patient safety by developing and qualifying higher-order reference measurement procedures for laboratory measurement standardization
  4. Review
  5. The role of AI in pre-analytical phase – use cases
  6. Opinion Paper
  7. Total laboratory automation: fit for its intended purposes?
  8. Guidelines and Recommendations
  9. EFLM checklist for the assessment of AI/ML studies in laboratory medicine: enhancing general medical AI frameworks for laboratory-specific applications
  10. Candidate Reference Measurement Procedures and Materials
  11. An isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedure for the quantification of cortisol in human serum and plasma
  12. Isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedures for the quantification of 24(R),25-dihydroxyvitamin D2 and 24(R),25-dihydroxyvitamin D3 in human serum and plasma
  13. An isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedure for the quantification of cortisone in human serum and plasma
  14. Candidate reference measurement procedure based on isotope dilution-two dimensional-liquid chromatography-tandem mass spectrometry for the quantification of androstenedione in human serum and plasma
  15. An isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedure for the quantification of 17β-estradiol in human serum and plasma
  16. Isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedures for the quantification of total and free phenytoin in human serum and plasma
  17. An isotope dilution-liquid chromatography-tandem mass spectrometry based candidate reference measurement procedure for the simultaneous quantification of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in human serum and plasma
  18. General Clinical Chemistry and Laboratory Medicine
  19. Quality assurance using patient split samples: recommendations for primary healthcare laboratories
  20. Age distorts the interpretation of FIB-4
  21. Not all anti-parietal cell antibody tests are equal for diagnosing pernicious anemia
  22. Impact of renal and hepatic function on dihydropyrimidine dehydrogenase phenotype assessed by enzyme activity in peripheral blood mononuclear cells and uracilemia
  23. Fecal leukocyte esterase levels predict endoscopic severity as an alternative biomarker in inflammatory bowel disease
  24. Cancer Diagnostics
  25. CA-125 glycovariant assays enhance diagnostic sensitivity in the detection of epithelial ovarian cancer
  26. Cardiovascular Diseases
  27. Defining the analytical characteristics of a novel high-sensitivity point-of-care troponin I assay in its intended clinical environment
  28. An automatic chemiluminescence immunoassay for a novel biomarker NT-IGFBP-4: analytical performance and clinical relevance in heart failure
  29. Analysis of total cholesterol results measured in the initial period of the Croatian screening program for familial hypercholesterolemia: a pilot study
  30. Diabetes
  31. Comparison of seven different enzymatic methods for serum glycated albumin in pregnant women: a multicenter study
  32. Infectious Diseases
  33. Comparative analysis of monocyte distribution width alterations in Escherichia coli sepsis: insights from in vivo and ex vivo models
  34. Proadrenomedullin for prediction of early and mid-term mortality in patients hospitalized for community-acquired pneumonia
  35. Annual Reviewer Acknowledgment
  36. Reviewer Acknowledgment
  37. Letters to the Editor
  38. Biological variation of serum Golgi protein 73 concentrations
  39. Are vitamins A and E results truly traceable and clinically useful? A practical and critical inquiry
  40. Tafasitamab interference in immunofixation electrophoresis
  41. Improvement in the turnaround time of PTH(1–84) as part of the intraoperative PTH monitoring for parathyroidectomy
  42. Rethinking the use of “one-way ANOVA” in CLSI EP15-A3 – a call for terminological precision and methodological clarity
  43. Toxic beauty: acute kidney injury triggered by hair-straightening treatment
  44. Congress Abstracts
  45. 57th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 29.12.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2025-0747/html
Scroll to top button