Comparison between fecal calprotectin and magnetic resonance enterography in ileal Crohn’s disease for activity disease assessment: a systematic review

Introduction

Crohn’s disease (CD) is a chronic nonspecific inflammatory condition of multifactorial etiology, characterized by periods of disease activity and remission, which can lead to irreversible tissue damage manifesting as strictures, abscesses, or fistulas (1,2). Management of the disease necessitates regular monitoring through clinical consultations and laboratory, radiographic, and endoscopic evaluations (3,4). Among the non-invasive methods for assessing disease activity, fecal calprotectin (FC) and magnetic resonance (MR) enterography are frequently utilized. However, while MR enterography is effective, it is often costly and not readily accessible for most patients. In contrast, FC is a more affordable and accessible alternative (5,6).

FC is a sensitive biomarker for assessing and monitoring CD (7). This calcium-binding protein exhibits antimicrobial properties and is primarily secreted by neutrophils (8). Its concentration in feces demonstrates a strong correlation with intestinal inflammation. The most commonly employed method for extracting FC from fecal samples is the enzyme-linked immunosorbent assay (ELISA). Typical reference values for FC concentrations are below 50 µg/g of feces for adults and children over 4 years of age. The recommended reference range for individuals aged 65 years and older is between 100 and 112 µg/g, reflecting lifestyle changes and age-related cellular alterations in the gastrointestinal mucosa (3,9). FC demonstrates high stability in fecal samples, enhancing its utility in clinical practice. Recent studies suggest that if FC measurement is conducted within 1 week, storing the samples at 4 ℃ is optimal (4,10-15).

MR enterography is a radiation-free diagnostic imaging modality characterized by its dynamic nature and high tissue resolution. This technique enables the assessment of intestinal motility, evaluation of disease activity, and detailed visualization of the intestinal wall, extending to the mucosal layer (16). Furthermore, it offers the advantage of evaluating adjacent structures and other abdominal organs within the same examination, providing a comprehensive assessment beyond the intestinal tract.

The objective of this study was to perform a systematic review (SR) exploring the correlation between FC levels and MR enterography findings in patients with ileal CD, as the association between these two diagnostic approaches remains unclear. We present this article in accordance with the PRISMA reporting checklist (available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-159/rc).

Methods

Study design

This SR evaluates scientific publications that satisfy specific eligibility criteria to address the research question: “Do FC levels correlate with findings from MR enterography in ileal CD?” The analysis was conducted following a structured methodology comprising the following steps: formulation of the research question, identification of databases, determination of the search range, specification of search components and descriptors, comprehensive and systematic database searches, establishment of inclusion and exclusion criteria, data collection, article selection, evaluation of eligibility, and application of exclusion criteria (17). The selected articles were thoroughly reviewed, and those failing to meet the inclusion criteria were excluded from the SR. Subsequently, the results were analyzed, and the findings and evidence were critically discussed. The protocol related to this RS is registered with PROSPERO (CRD42024546026).

Research strategy, screening, and data extraction

The Rayyan system was utilized to select studies and export data. Rayyan, a software developed by the Qatar Computing Research Institute (QCRI), is a tool for archiving, organizing, and selecting articles (18). The systematic search for articles within the databases commenced in May 2021 and concluded on October 27, 2024, yielding 757 articles retrieved in English.

Two reviewers, working autonomously and independently, selected articles within the Rayyan system. In cases of contradictory or conflicting decisions, a third reviewer analyzed the discrepancies and decided whether an article should be included or excluded. The database search encompassed PubMed, PubMed PMC, BVS-BIREME, Scopus, Web of Science, EMBASE, and the Cochrane Library (Table 1).

Inclusion and exclusion criteria

The descriptors and free terms included in the search strategy were “Crohn disease”, “fecal calprotectin”, “fecal calprotectin test”, “faecal calprotectin test”, “faecal calprotectin”, “magnetic resonance enterography (MRE)”, “Magnetic resonance enterography”, “MR enterography”, and “MRI enterography”. These terms were selected after an in-depth review of materials relevant to the research topic. Boolean operators “OR” and “AND” were employed to connect descriptors and free terms, enabling a broader yet focused search across databases. Specifically, these operators were utilized to either expand or narrow the search as follows: “Crohn disease” AND (“fecal calprotectin” OR “fecal calprotectin test” OR “faecal calprotectin test” OR “faecal calprotectin”) AND (“magnetic resonance enterography (MRE)” OR “Magnetic resonance enterography” OR “MR enterography” OR “MRI enterography”).

This review was further characterized by the definition of the target population (participants), types of interventions and comparisons, and the implications of the findings. The PICO framework—an acronym for Population, Interventions, Comparators, and Outcomes—was systematically applied as a guiding structure for this type of research. The main aspects of interest in this SR, structured using the PICO framework, are detailed in Table 2, which outlines the study design. The inclusion criteria for this study were defined as follows: investigations conducted in human subjects, focusing on patients with ileal CD older than 18 years, and studies examining correlations between FC levels and findings from MR enterography. Exclusion criteria encompassed studies involving pediatric populations, SRs, meta-analyses, and patients diagnosed with CD restricted to locations other than the ileum. This study included only patients with isolated ileal CD; patients who had ileocecal or colonic disease were excluded from the SR.

Results

The search strategy was conducted across seven databases, with the final investigation updated on October 27, 2024. It initially retrieved 1.039 articles published between 2010 and 2023. These references were imported into the EndNote™ platform (https://endonote.com/), where 282 duplicates were automatically removed.

A total of 74 studies were identified in PubMed; 482 in PubMed PMC; 65 in BVS/BIREME (MEDLINE—63, LILACS—1, WPRIM-Western Pacific—1); 92 in Scopus; 133 in Web of Science; 179 in EMBASE; and 14 in the Cochrane Library. After duplicate removal, 757 unique articles remained for screening by title and abstract in alignment with the study’s objectives.

Subsequently, the research flowchart steps and article selection process were applied (Figure 1), resulting in eight studies deemed relevant for interpretative analysis based on the eligibility criteria. All eight articles included in this SR were published in English, and the studies were conducted in several countries: England (n=1), Spain (n=2), Poland (n=1), China (n=1), Scotland (n=1), Portugal (n=1), and Romania (n=1).

Figure 1 Study flowchart design. Total references were obtained from the databases, and the final number of studies was included in the systematic review. CD, Crohn’s disease; FC, fecal calprotectin; MR, magnetic resonance.

The studies encompassed 845 participants, of whom 384 had ileal CD and were eligible for the combination of FC with MR enterography. In terms of study design, all articles were observational, comprising three prospective and five retrospective cohort studies. Tables 3,4 present the objectives and key findings of the studies included in the SR. Concerning FC immunoassays, five studies utilized the ELISA, one employed the fluoroenzyme immunoassay (FEIA), another used the immunochromatography test, and one study did not specify the test used. Regarding MR enterography scoring systems, three studies applied the magnetic resonance index of activity (MaRIA), two employed the simplified magnetic resonance index of activity (sMaRIA), two used the simple enterography activity score for Crohn’s disease (SEAS-CD), and one utilized the magnetic resonance enterography global score (MEGS). A summary of the immunoassays and MR enterography scores is provided in Figure 2.

Figure 2 Summary of the methods used to correlate FC and MR enterography in the studies included in the SR (19-26). Created with BioRender.com. CD, Crohn’s disease; ELISA, enzyme-linked immunosorbent assay; FC, fecal calprotectin; FEIA, flouroenzyme immunoassay; MaRIA, magnetic resonance index of activity; MEGS, magnetic resonance enterography global score; MR, magnetic resonance; SEAS-CD, simple enterographic activity score for Crohn’s disease; sMaRIA, simplified magnetic resonance index of activity.

The interval between FC and MR enterography in the studies was up to three months. In two studies (19,21) they were performed on the same day; two (22,26) within up to one week; one (20) within up to two weeks; one (23) within up to four weeks, one (24) between two and four weeks; and another study (25) within up to three months between the exams. Of the eight studies included in this SR, seven showed a positive correlation between FC and MR enterography in ileal CD. In contrast, only one study did not demonstrate a correlation between the two exams (Table 5).

Discussion

Calprotectin is an antimicrobial protein secreted by neutrophils (7,8), and its fecal concentration may be associated with various gastrointestinal disorders, including inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and CD (27). Due to its low cost and non-invasive nature, calprotectin has been widely used for diagnosing and monitoring CD. Furthermore, it demonstrates superior performance compared to blood-based biomarkers, such as C-reactive protein (CRP), leukocyte count, and erythrocyte sedimentation rate (ESR) (28-31). FC is a non-invasive biomarker with good diagnostic accuracy for detecting active CD in MR enterography, both in overall bowel inflammation or disease localized in the ileum (32). However, FC values may vary depending on the location of the inflammation; in colonic CD, FC levels tend to be higher than in small intestine CD (33).

FC cutoff values for the diagnosis and activity assessment of ileal CD

Among the studies included in this SR, various cut-off values of FC were identified for determining the diagnosis of active ileal CD, ranging from >100 to >430 µg/g of feces. Makanyanga et al. (19) observed that an FC cut-off value >100 µg/g of feces indicates disease activity, with a sensitivity of 65% and specificity of 78%. Cerrillo et al. (20) reported a cut-off value of 166.50 µg/g, with a sensitivity of 90.48% and specificity of 74.29%. In the study by Stawczyk-Eder et al. (21), FC levels for disease activity ranged from 114.9±77.4 mg/L of feces. Ye et al. (22) demonstrated that FC correlates strongly with mucosal healing, with a cut-off value of 170.2 µg/g of feces, exhibiting sensitivity of 80% and specificity of 70%.

Jones et al. (23), when classifying disease activity as absent, mild to moderate, and severe, in correlation with MR enterography, found median FC values of 80 µg/g, 198 µg/g, and 360 µg/g of feces, respectively (P<0.001). Conversely, Roseira et al. (24) found median FC values of 23 µg/g in remission, 358 µg/g in active disease, and 1.001 µg/g in severe disease (P<0.001). However, these values refer to ileal, colonic and ileocolonic CD. FC levels were not reported separately for ileal CD. Romero-Mascarell et al. (25) identified a cut-off value of FC >430 µg/g as predictive of lesions on MR enterography in patients with ileal CD, with a sensitivity of 72% and specificity of 73%. Statie et al. (26) used a reference of FC >250 µg/g to indicate active ileal CD.

FC shows a good correlation with both the clinical assessment of CD and endoscopic evaluation. A study carried out by Li et al. (31) involving 273 patients found that FC correlated positively with the Crohn’s disease activity index (CDAI) and with the Simple Endoscopic Score for Crohn’s Disease (SES-CD), with correlation coefficients of 0.666 and 0.674, respectively. The authors found that FC proved to be an effective and reliable biomarker for assessing endoscopic disease activity in CD patients, including those with ileal involvement. FC has also been correlated with capsule endoscopy and balloon-assisted enteroscopy to assess CD activity in the small intestine. Sousa et al. (34), in a study with 196 patients (92% with ileal CD), found that FC levels showed a moderate correlation with small intestine capsule endoscopy (Lewis score ≥135); however, they did not show high sensitivity and specificity, but considered it a reasonable marker to predict significant inflammatory lesions.

Regarding the association between endoscopic examination and MR enterography in the evaluation of ileal CD, Kakkar et al. (35) state that colonoscopy is still the gold standard for evaluating CD of the terminal ileum and that MR enterography is a sensitive examination for severe cases of the disease but not for mild cases. MR enterography has the advantage to being able to identify transmural disease activity, even when the mucosa appears normal on endoscopic examination. The combination of the two examinations is ideal for evaluating the extension of the disease.

A factor that may influence FC measurement in feces is the variability of immunoassays available on the market. Additionally, it is suggested that the differences in FC values used for determining CD disease activity may be attributed to the distinct populations included in the studies (36). Among the analytical methods for measuring FC are chemiluminescence immunoassay (CLIA), ELISA (polyclonal/monoclonal), FEIA, latex agglutination turbidimetric immunoassay (LATIA), lateral flow immunochromatographic immunoassay (LFIA), and particle-enhanced turbidimetric immunoassay (PETIA), with normal FC values ranging from <47 to <80 µg/g. Consequently, most assays use a cut-off value of 50 µg/g to indicate intestinal mucosal inflammation (9,15).

Due to variations in cut-off values across different immunoassays, it is recommended that patients requiring serial FC measurements always utilize the same assay (15). A study comparing six automated immunoassays with a cut-off of 50 µg/g proposed by the manufacturers showed good diagnostic accuracy, with a sensitivity of 100% and a specificity ranging from 58.4% to 78.5%, for detecting IBD (7). Another recent study by Kapel et al. (37) suggests no consensus exists on the ideal FC cut-off value for diagnosing active IBD. Concentrations between 50 and 250 µg/g of feces are considered difficult to interpret, and patients with these FC levels should be closely monitored. In comparison, those with levels exceeding 250 µg/g require more frequent monitoring and additional tests to assess disease activity.

Recently, in an important update to the STRIDE (Selecting Therapeutic Targets in Inflammatory Bowel Disease, STRIDE II) recommendations, an FC cut-off value of 150 µg/g was proposed for CD in remission and 250 µg/g for active CD (37).

Another factor that may affect FC measurement in feces is the method of sample storage before testing. Initial studies indicated that FC remains stable in feces for up to 7 days at room temperature (4,10-13). However, more recent research shows that FC concentration in feces decreases by up to 28% after 7 days at room temperature, and measurement at room temperature should be limited to a maximum of 3 days (15). Other authors recommend storing stool samples at 4 ℃ for up to 1 week (14). If samples cannot be processed within 1 week, they should be frozen at −20 ℃ (15).

FC levels in ileal CD and relation with MR enterography

When analyzing the correlation between FC levels and MR enterography, it was observed that seven studies (19-21,23-26) reported a positive correlation between FC levels and MR enterography scores. In contrast, a single study by Ye et al. (24) found no correlation between these two tests. Makanyanga et al. (19) demonstrated a significant positive correlation between the MEGS and FC (r=0.458; P<0.001), with a cutoff value for active CD set at FC >100 µg/g of feces, an area under the curve (AUC) of 0.75 [95% confidence interval (CI): 0.62–0.88], sensitivity of 65%, and specificity of 78%. Cerrillo et al. (20) identified a significant positive correlation between MaRIA score and FC levels (r=0.56; P<0.001), with an FC cutoff value of 166.50 µg/g of feces, a sensitivity of 90.48% (95% CI: 82.32–95.09%), and a specificity of 74.29% (95% CI: 57.93–85.84%) for predicting disease activity. The positive and negative predictive values were 89.41% and 76.47%, respectively.

Stawczyk-Eder et al. (21) examined the utility of FC in different intestinal segments in CD. In patients with ileal involvement, FC levels averaged 114.9±77.4 mg/L of feces, significantly correlating with the SEAS-CD score (r=0.35; P=0.03). Roseira et al. (24), in a study of 84 patients with CD (45.24% with ileal disease), found an excellent correlation between the sMARIA and FC (r=0.91; P<0.001). This strong correlation was maintained in separate analyses for ileal, colonic, and ileocolonic CD (r=0.88, r=0.92, r=0.88, respectively; P<0.001).

Moreover, Ye et al. (22) studied 221 CD patients (51 with the disease only in the ileum). Of these, 29 patients were eligible for the correlation analysis between FC and MaRIA. They found no significant correlation between MR enterography scores and FC levels (r=0.230; P=0.23), although FC levels were strongly correlated with mucosal healing, with a cutoff value of 170.2 µg/g of feces, sensitivity of 80%, and specificity of 70%. In a study by Jones et al. (23), which evaluated 119 MR enterography exams from 104 patients with ileal CD (110 also had FC measurements), disease activity was classified as absent, mild to moderate, or severe for both MR enterography and FC. The total score for MR enterography ranged from 0 to 6, with 0 indicating no disease, 1–6 indicating mild to moderate disease, and >6 indicating severe disease. Median FC values were 80 µg/g (range, 19–165 µg/g) for absent disease, 198 µg/g (range, 101–486 µg/g) for mild to moderate disease, and 360 µg/g (range, 170–760 µg/g) for severe disease. This study showed a positive correlation between FC levels and MR enterography scores in predicting ileal CD activity. Regarding disease monitoring, FC was found to predict biologic-free progression over three years, while MR enterography strongly predicted the risk of surgery and long-term biologic treatment.

Romero-Mascarell et al. (25), in their analysis of the correlation between FC levels and inflammatory activity in small bowel CD using capsule endoscopy or MR enterography, found a moderate correlation between FC and MR enterography (r²=0.5; P=0.001) in the group evaluated with MR enterography. FC levels were significantly higher in patients with lesions detected by MR enterography compared to those without lesions (944.9±672.1 vs. 221±212.2 µg/g of feces, P<0.05). Similarly, Statie et al. (26) correlated contrast-enhanced intestinal ultrasound with MR enterography, clinical assessments, and fecal biomarkers in patients with ileal CD. They observed a significant correlation between FC levels and MR enterography scores (r=0.697; P<0.001) and found that MR enterography was more strongly correlated with clinical scores and FC than ultrasound.

Most studies indicate a strong correlation between FC and imaging findings, such as those from computed tomography (CT) and MR enterography. A prospective pilot study by Domachevsky et al. (38), involving 21 individuals, demonstrated that combined metrics of positron emission tomography and CT (PET-CT) and MR enterography, along with the apparent diffusion coefficient and metabolic inflammatory volume, were associated with biomarkers such as FC and CRP to distinguish between active and in remission CD, with a sensitivity of 83% and specificity of 100%. In this study, FC levels greater than 150 µg/g of feces indicated active disease.

Klang et al. (39), in a study of 52 patients, examined the relationship between FC levels and MR enterography using diffusion-weighted imaging in small bowel CD in clinical remission or with mild symptoms. They found that FC levels were higher in patients exhibiting restricted diffusion than in those without diffusion abnormalities. Pendsé et al. (40) investigated whether qualitative assessment of the enteric diffusion signal could reflect the overall inflammatory burden, using FC and a validated MR activity score as reference standards. They found that FC levels were significantly lower in patients with abnormal diffusion restricted to less than 10 cm of the small bowel than those with abnormal diffusion involving both the small bowel and colon.

Lopes et al. (41) found that FC significantly correlated with endoscopic activity and CT enterography findings of inflammatory activity in newly diagnosed CD patients one year after the initiation of immunosuppressive therapy (r=0.596; P<0.001). Disease location did not affect the accuracy of FC measurements in the terminal ileum (r=0.695; P<0.001) or ileocolonic CD (r=0.678; P<0.001). Another prospective study by Shimoyama et al. (42) evaluated the utility of fecal biomarkers for detecting small bowel inflammation and reported a significant positive correlation between fecal biomarkers and CT enterography scores.

In patients with CD limited to the colon, Somwaru et al. (16) found a positive correlation between FC levels and MR enterography (MaRIA score) and colonoscopy, with an FC cutoff value of 250 µg/g of feces indicating active disease. They reported an area under the receiver operating characteristic curve (AUROC) of 0.92 and 0.92, a sensitivity of 92% and 92%, and a specificity of 83% and 85%, respectively. However, Abej et al. (43) found no correlation between FC and MR or CT enterography in 183 adult and pediatric patients with IBD.

Lorenc-Góra et al. (44) analyzed the association between MR enterography and biomarkers, including FC, CRP, and blood count. Their findings demonstrated a positive correlation between MR enterography findings and all three biomarker types. The authors also concluded that combining these methods can improve the accuracy of CD diagnosis and they enable more effective disease monitoring, thereby reducing the necessity for unnecessary invasive exams.

One of the primary limitations of this study was the small number of studies included in the analysis, most of which did not focus on exclusive cohorts of patients with ileal CD. Furthermore, the studies assessed lacked standardized scores to measure CD activity on MR enterography, employing quantitative (SEAS-CD, MaRIA, sMaRIA) and qualitative (MEGS) methods. Due to these limitations, this SR was descriptive rather than comparative. Nevertheless, the findings remain significant, as they highlight the relevance of FC for diagnosing active CD, demonstrating a positive correlation with MR enterography. However, further studies with larger cohorts of patients with ileal CD are needed to confirm and strengthen these results.

Conclusions

In the studies reviewed, the cutoff values of FC for predicting ileal CD activity were found to be diverse. FC levels in ileal CD were lower than in patients with ileocolonic or sole colonic involvement. In most studies, FC demonstrated a positive correlation with the findings of MR enterography.

Acknowledgments

We thank Tristan Torriani for revising the English revision of our manuscript. We thank Ana Paula de Morais for helping us to search the articles in the databases.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-159/rc

Peer Review File: Available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-159/prf

Funding: This work was supported by the National Council for Scientific and Technological Development (CNPq) (No. 302557/2021-0 to R.F.L.) and São Paulo Research Foundation (FAPESP) (No. 2020/01924-5 to L.M.G).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-24-159/coif). D.L.M. reports the payment or honoraria as a consultant in the field of Radiology/Diagnostic Imaging from Bayer S.A. and the support for attending the RSNA meeting from Diagnóstico da América S.A. (DASA). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work and ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Petagna L, Antonelli A, Ganini C, et al. Pathophysiology of Crohn's disease inflammation and recurrence. Biol Direct 2020;15:23. [Crossref] [PubMed]
2. Wan J, Zhou J, Wang Z, et al. Epidemiology, pathogenesis, diagnosis, and treatment of inflammatory bowel disease: Insights from the past two years. Chin Med J (Engl) 2025;138:763-76. [Crossref] [PubMed]
3. Torres J, Mehandru S, Colombel JF, et al. Crohn's disease. Lancet 2017;389:1741-55. [Crossref] [PubMed]
4. Manceau H, Chicha-Cattoir V, Puy H, et al. Fecal calprotectin in inflammatory bowel diseases: update and perspectives. Clin Chem Lab Med 2017;55:474-83. [Crossref] [PubMed]
5. Veauthier B, Hornecker JR. Crohn's Disease: Diagnosis and Management. Am Fam Physician 2018;98:661-9.
6. Asiri AS, Algarni SS, Althubaiti AQ, et al. Fecal Calprotectin and Organic Gastrointestinal Disease: A Systematic Review. Cureus 2023;15:e45019. [Crossref] [PubMed]
7. Mumolo MG, Bertani L, Ceccarelli L, et al. From bench to bedside: Fecal calprotectin in inflammatory bowel diseases clinical setting. World J Gastroenterol 2018;24:3681-94. [Crossref] [PubMed]
8. Rodrigo L. Fecal calprotectin. Rev Esp Enferm Dig 2007;99:683-8. [Crossref] [PubMed]
9. Ayling RM, Kok K. Fecal Calprotectin. Adv Clin Chem 2018;87:161-90. [Crossref] [PubMed]
10. Ikhtaire S, Shajib MS, Reinisch W, et al. Fecal calprotectin: its scope and utility in the management of inflammatory bowel disease. J Gastroenterol 2016;51:434-46. [Crossref] [PubMed]
11. Panes J, Jairath V, Levesque BG. Advances in Use of Endoscopy, Radiology, and Biomarkers to Monitor Inflammatory Bowel Diseases. Gastroenterology 2017;152:362-373.e3. [Crossref] [PubMed]
12. Pathirana WGW, Chubb SP, Gillett MJ, et al. Faecal Calprotectin. Clin Biochem Rev 2018;39:77-90.
13. Khaki-Khatibi F, Qujeq D, Kashifard M, et al. Calprotectin in inflammatory bowel disease. Clin Chim Acta 2020;510:556-65. [Crossref] [PubMed]
14. Hamer HM, Mulder AHL, de Boer NK, et al. Impact of Preanalytical Factors on Calprotectin Concentration in Stool: A Multiassay Comparison. J Appl Lab Med 2022;7:1401-11. [Crossref] [PubMed]
15. Murray J, Kok KB, Ayling RM. Fecal Calprotectin in Gastrointestinal Disease. Clin Chem 2023;69:699-710. [Crossref] [PubMed]
16. Somwaru AS, Khanijow V, Katabathina VS. Magnetic resonance enterography, colonoscopy, and fecal calprotectin correlate in colonic Crohn's disease. BMC Gastroenterol 2019;19:210. [Crossref] [PubMed]
17. Mello JDC, Gomes LEM, Silva JF, et al. The role of chemokines and adipokines as biomarkers of Crohn's disease activity: a systematic review of the literature. Am J Transl Res 2021;13:8561-74.
18. Ouzzani M, Hammady H, Fedorowicz Z, et al. Rayyan-a web and mobile app for systematic reviews. Syst Rev 2016;5:210. [Crossref] [PubMed]
19. Makanyanga JC, Pendsé D, Dikaios N, et al. Evaluation of Crohn's disease activity: initial validation of a magnetic resonance enterography global score (MEGS) against faecal calprotectin. Eur Radiol 2014;24:277-87. [Crossref] [PubMed]
20. Cerrillo E, Beltrán B, Pous S, et al. Fecal Calprotectin in Ileal Crohn's Disease: Relationship with Magnetic Resonance Enterography and a Pathology Score. Inflamm Bowel Dis 2015;21:1572-9. [Crossref] [PubMed]
21. Stawczyk-Eder K, Eder P, Lykowska-Szuber L, et al. Is faecal calprotectin equally useful in all Crohn's disease locations? A prospective, comparative study. Arch Med Sci 2015;11:353-61. [Crossref] [PubMed]
22. Ye L, Cheng W, Chen BQ, et al. Levels of Faecal Calprotectin and Magnetic Resonance Enterocolonography Correlate with Severity of Small Bowel Crohn's Disease: A Retrospective Cohort Study. Sci Rep 2017;7:1970. [Crossref] [PubMed]
23. Jones GR, Fascì-Spurio F, Kennedy NA, et al. Faecal Calprotectin and Magnetic Resonance Enterography in Ileal Crohn's Disease: Correlations Between Disease Activity and Long-Term Follow-Up. J Crohns Colitis 2019;13:442-50. [Crossref] [PubMed]
24. Roseira J, Ventosa AR, de Sousa HT, et al. The new simplified MARIA score applies beyond clinical trials: A suitable clinical practice tool for Crohn's disease that parallels a simple endoscopic index and fecal calprotectin. United European Gastroenterol J 2020;8:1208-16. [Crossref] [PubMed]
25. Romero-Mascarell C, Fernández-Esparrach G, Rodríguez-De Miguel C, et al. Fecal Calprotectin for Small Bowel Crohn's Disease: Is It a Cutoff Issue? Diagnostics (Basel) 2022;12:2226. [Crossref] [PubMed]
26. Statie RC, Iordache S, Florescu LM, et al. Assessment of Ileal Crohn's Disease Activity by Gastrointestinal Ultrasound and MR Enterography: A Pilot Study. Life (Basel) 2023;13:1754. [Crossref] [PubMed]
27. Mari A, Baker FA, Mahamid M, et al. Clinical utility of fecal calprotectin: potential applications beyond inflammatory bowel disease for the primary care physician. Ann Gastroenterol 2019;32:425-30. [Crossref] [PubMed]
28. Kyle BD, Agbor TA, Sharif S, et al. Fecal Calprotectin, CRP and Leucocytes in IBD Patients: Comparison of Biomarkers With Biopsy Results. J Can Assoc Gastroenterol 2021;4:84-90. [Crossref] [PubMed]
29. Bryce C, Bucaj M. Fecal Calprotectin for the Evaluation of Inflammatory Bowel Disease. Am Fam Physician 2021;104:303-4.
30. Seo J, Song S, Shin SH, et al. Fecal Calprotectin in Patients with Crohn's Disease: A Study Based on the History of Bowel Resection and Location of Disease. Diagnostics (Basel) 2024;14:854. [Crossref] [PubMed]
31. Li J, Xu M, Qian W, et al. Clinical value of fecal calprotectin for evaluating disease activity in patients with Crohn's disease. Front Physiol 2023;14:1186665. [Crossref] [PubMed]
32. Smith ES, Chen J, Pan Y, et al. The Relationship Between the Endoscopic Healing Index, Fecal Calprotectin, and Magnetic Resonance Enterography in Crohn's Disease. J Clin Gastroenterol 2024;58:607-13. [Crossref] [PubMed]
33. Ukashi O, Kopylov U, Ungar B, et al. Fecal Calprotectin Diagnostic Level Gradient Along the Small Bowel in Patients With Crohn's Disease. J Crohns Colitis 2025;19:jjae123. [Crossref] [PubMed]
34. Sousa MI, Dias E, Andrade P, et al. Fecal calprotectin as an inflammatory biomarker in small bowel Crohn disease. Porto Biomed J 2024;9:263. [Crossref] [PubMed]
35. Kakkar C, Singh A, Mahajan R, et al. Correlation between magnetic resonance enterography and ileo-colonoscopy for assessment of disease activity in terminal ileal Crohn's disease. Indian J Gastroenterol 2022;41:465-74. [Crossref] [PubMed]
36. Bahaa A, Elbaz T, Elmakhzangy H, et al. Assessment of IBD disease activity by Interleukin-6 and serum amyloid A in relation with fecal calprotectin and endoscopic indices. Arab J Gastroenterol 2024;25:299-305. [Crossref] [PubMed]
37. Kapel N, Ouni H, Benahmed NA, et al. Fecal Calprotectin for the Diagnosis and Management of Inflammatory Bowel Diseases. Clin Transl Gastroenterol 2023;14:e00617. [Crossref] [PubMed]
38. Domachevsky L, Leibovitzh H, Avni-Biron I, et al. Correlation of 18F-FDG PET/MRE Metrics with Inflammatory Biomarkers in Patients with Crohn's Disease: A Pilot Study. Contrast Media Mol Imaging 2017;2017:7167292. [Crossref] [PubMed]
39. Klang E, Kopylov U, Eliakim R, et al. Diffusion-weighted imaging in quiescent Crohn's disease: correlation with inflammatory biomarkers and video capsule endoscopy. Clin Radiol 2017;72:798.e7-798.e13. [Crossref] [PubMed]
40. Pendsé DA, Makanyanga JC, Plumb AA, et al. Diffusion-weighted imaging for evaluating inflammatory activity in Crohn's disease: comparison with histopathology, conventional MRI activity scores, and faecal calprotectin. Abdom Radiol (NY) 2017;42:115-23. [Crossref] [PubMed]
41. Lopes S, Andrade P, Afonso J, et al. Monitoring Crohn's disease activity: endoscopy, fecal markers and computed tomography enterography. Therap Adv Gastroenterol 2018;11:1756284818769075. [Crossref] [PubMed]
42. Shimoyama T, Yamamoto T, Umegae S, et al. Faecal biomarkers for screening small bowel inflammation in patients with Crohn's disease: a prospective study. Therap Adv Gastroenterol 2017;10:577-87. [Crossref] [PubMed]
43. Abej E, El-Matary W, Singh H, et al. The Utility of Fecal Calprotectin in the Real-World Clinical Care of Patients with Inflammatory Bowel Disease. Can J Gastroenterol Hepatol 2016;2016:2483261. [Crossref] [PubMed]
44. Lorenc-Góra J, Waniczek D, Czuba ZP, et al. Assessment of the Utility of Selected Inflammatory Markers in Correlation with Magnetic Resonance Enterography (MRE) Findings in the Diagnosis of Crohn's Disease. Biomolecules 2025;15:116. [Crossref] [PubMed]