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Costa MHDM, Sassaki LY, Chebli JMF. Fecal calprotectin and endoscopic scores: The cornerstones in clinical practice for evaluating mucosal healing in inflammatory bowel disease. World J Gastroenterol 2024; 30:3022-3035. [PMID: 38983953 PMCID: PMC11230062 DOI: 10.3748/wjg.v30.i24.3022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 05/01/2024] [Accepted: 05/27/2024] [Indexed: 06/25/2024] Open
Abstract
Managing inflammatory bowel disease (IBD) is becoming increasingly complex and personalized, considering the advent of new advanced therapies with distinct mechanisms of action. Achieving mucosal healing (MH) is a pivotal therapeutic goal in IBD management and can prevent IBD progression and reduce flares, hospitalization, surgery, intestinal damage, and colorectal cancer. Employing proactive disease and therapy assessment is essential to achieve better control of intestinal inflammation, even if subclinical, to alter the natural course of IBD. Periodic monitoring of fecal calprotectin (FC) levels and interval endoscopic evaluations are cornerstones for evaluating response/remission to advanced therapies targeting IBD, assessing MH, and detecting subclinical recurrence. Here, we comment on the article by Ishida et al Moreover, this editorial aimed to review the role of FC and endoscopic scores in predicting MH in patients with IBD. Furthermore, we intend to present some evidence on the role of these markers in future targets, such as histological and transmural healing. Additional prospective multicenter studies with a stricter MH criterion, standardized endoscopic and histopathological analyses, and virtual chromoscopy, potentially including artificial intelligence and other biomarkers, are desired.
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Affiliation(s)
| | - Ligia Yukie Sassaki
- Department of Internal Medicine, Medical School, São Paulo State University (Unesp), Botucatu 18618-686, São Paulo, Brazil
| | - Júlio Maria Fonseca Chebli
- Division of Gastroenterology, Department of Medicine, University Hospital of The Federal University of Juiz de Fora, University of Juiz de Fora School of Medicine, Juiz de Fora 36036-247, Minas Gerais, Brazil
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Gubatan J, Holman DR, Puntasecca CJ, Polevoi D, Rubin SJS, Rogalla S. Antimicrobial peptides and the gut microbiome in inflammatory bowel disease. World J Gastroenterol 2021; 27:7402-7422. [PMID: 34887639 PMCID: PMC8613745 DOI: 10.3748/wjg.v27.i43.7402] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/13/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
Antimicrobial peptides (AMP) are highly diverse and dynamic molecules that are expressed by specific intestinal epithelial cells, Paneth cells, as well as immune cells in the gastrointestinal (GI) tract. They play critical roles in maintaining tolerance to gut microbiota and protecting against enteric infections. Given that disruptions in tolerance to commensal microbiota and loss of barrier function play major roles in the pathogenesis of inflammatory bowel disease (IBD) and converge on the function of AMP, the significance of AMP as potential biomarkers and novel therapeutic targets in IBD have been increasingly recognized in recent years. In this frontier article, we discuss the function and mechanisms of AMP in the GI tract, examine the interaction of AMP with the gut microbiome, explore the role of AMP in the pathogenesis of IBD, and review translational applications of AMP in patients with IBD.
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Affiliation(s)
- John Gubatan
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Redwood City, CA 94063, United States
| | - Derek R Holman
- Department of Radiology, Molecular Imaging Program at Stanford , Stanford University, Stanford , CA 94305, United States
| | | | - Danielle Polevoi
- Stanford University School of Medicine, Stanford University, Stanford, CA 94063, United States
| | - Samuel JS Rubin
- Stanford University School of Medicine, Stanford University, Stanford, CA 94063, United States
| | - Stephan Rogalla
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Redwood City, CA 94063, United States
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Bromke MA, Neubauer K, Kempiński R, Krzystek-Korpacka M. Faecal Calprotectin in Assessment of Mucosal Healing in Adults with Inflammatory Bowel Disease: A Meta-Analysis. J Clin Med 2021; 10:jcm10102203. [PMID: 34069684 PMCID: PMC8161009 DOI: 10.3390/jcm10102203] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 05/12/2021] [Accepted: 05/15/2021] [Indexed: 12/12/2022] Open
Abstract
Achieving mucosal healing in patients with inflammatory bowel disease is related to a higher incidence of sustained clinical remission and it translates to lower rates of hospitalisation and surgery. The assessment methods of disease activity and response to therapy are limited and mainly rely on colonoscopy. This meta-analysis reviews the effectiveness of using faecal calprotectin as a marker for mucosal healing in inflammatory bowel disease. Two meta-analyses were conducted in parallel. The analysis on the use of faecal calprotectin in monitoring mucosal healing in colonic Crohn’s disease is based on 16 publications (17 studies). The data set for diagnostic values of faecal calprotectin in ulcerative colitis is composed of 35 original publications (total 49 studies). The DOR for the use of faecal calprotectin in Crohn’s disease is estimated to be 11.20 and the area under the sROCis 0.829. In cases of ulcerative colitis, the DOR is 14.48, while the AUC sROC is 0.858. Heterogeneity of the studies was moderatetosubstantial. Collected data show overall good sensitivity and specificity of the faecal calprotectin test, as well as a good DOR. Thus, monitoring of mucosal healing with a non-invasive faecal calprotectin test may represent an attractive option for physicians and patients with inflammatory bowel disease.
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Affiliation(s)
- Mariusz A. Bromke
- Department of Biochemistry and Immunochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland;
- Correspondence:
| | - Katarzyna Neubauer
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (K.N.); (R.K.)
| | - Radosław Kempiński
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (K.N.); (R.K.)
| | - Małgorzata Krzystek-Korpacka
- Department of Biochemistry and Immunochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland;
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Krzystek-Korpacka M, Kempiński R, Bromke M, Neubauer K. Biochemical Biomarkers of Mucosal Healing for Inflammatory Bowel Disease in Adults. Diagnostics (Basel) 2020; 10:E367. [PMID: 32498475 PMCID: PMC7344443 DOI: 10.3390/diagnostics10060367] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 05/29/2020] [Accepted: 05/30/2020] [Indexed: 02/06/2023] Open
Abstract
Mucosal healing (MH) is the key therapeutic target of inflammatory bowel disease (IBD). The evaluation of MH remains challenging, with endoscopy being the golden standard. We performed a comprehensive overview of the performance of fecal-, serum-, and urine-based biochemical markers in colonic IBD to find out whether we are ready to replace endoscopy with a non-invasive but equally accurate instrument. A Pubmed, Web of Knowledge, and Scopus search of original articles as potential MH markers in adults, published between January 2009 and March 2020, was conducted. Finally, 84 eligible studies were identified. The most frequently studied fecal marker was calprotectin (44 studies), with areas under the curves (AUCs) ranging from 0.70 to 0.99 in ulcerative colitis (UC) and from 0.70 to 0.94 in Crohn`s disease (CD), followed by lactoferrin (4 studies), matrix metalloproteinase-9 (3 studies), and lipocalin-2 (3 studies). The most frequently studied serum marker was C-reactive protein (30 studies), with AUCs ranging from 0.60 to 0.96 in UC and from 0.64 to 0.93 in CD. Fecal calprotectin is an accurate MH marker in IBD in adults; however, it cannot replace endoscopy and the application of calprotectin is hampered by the lack of standardization concerning the cut-off value. Other markers are either not sufficiently accurate or have not been studied extensively enough.
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Affiliation(s)
| | - Radosław Kempiński
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland;
| | - Mariusz Bromke
- Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland;
| | - Katarzyna Neubauer
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland;
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Assessment of the usefulness of imaging studies and biomarkers in the activity of Crohn's disease. GASTROENTEROLOGY REVIEW 2020; 16:15-22. [PMID: 33986883 PMCID: PMC8112266 DOI: 10.5114/pg.2020.93539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 02/16/2020] [Indexed: 11/17/2022]
Abstract
Aim The aim of the study was to determine the suitability of available diagnostic methods, by means of comparison, for predicting disease activity, based on cost efficiency and sensitivity criteria. Material and methods In this study, we conducted analyses of 37 patients with Crohn’s disease (CD). CD was graded as “active” or “inactive” by adopting certain cut-off values for every marker. The main assumption was that methods used to grade CD severity do not give false positive results. The authors decided to measure the agreement between the methods by applying Cohen’s κ coefficient. Results Endoscopy shows the highest sensitivity, negative predictive value, and accuracy in detecting CD. In the case of both intestines, the sensitivity of endoscopy reached 93.9% and the accuracy 94.6%, while the sensitivity and accuracy of enterography and calprotectin were 51.5% vs. 71,9% and 56.8% vs. 72.2%, respectively. For the large intestine, the sensitivity and accuracy of endoscopy reached 100%. For the small intestine, endoscopy had 55% sensitivity and 75% accuracy, while enterography showed only 66.7% and 81.1%, respectively. The best agreement (77.1%, p = 0.005) was seen between endoscopy and calprotectin for full intestines. However, the value of Cohen’s κ suggests that this agreement is moderate. The optimal cut-off value for calprotectin was 43 µg/g, and the ROC curve (AUC = 0.871) was large enough to conclude that calprotectin is a statistically significant (p < 0.001) indicator of CD activity. Conclusions Statistically significant compliance was shown only between colonoscopy and faecal calprotectin.
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Role of fecal calprotectin as a biomarker of intestinal inflammation in ulcerative colitis: a prospective study. REV ROMANA MED LAB 2018. [DOI: 10.2478/rrlm-2018-0006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Abstract
Background: The clinical utility of non-invasive markers in the diagnosis and monitoring of ulcerative colitis (UC) has been intensively studied. The aim of our study was to evaluate the value of fecal calprotectin (FC) in differentiating between UC and irritable bowel syndrome (IBS), and in estimating inflammatory activity in UC.
Method: A total number of 140 patients were included in the study. All patients underwent ileocolonoscopy with biopsies, quantitative determination of FC, and blood tests (white blood cell count, CRP, ESR). The severity of UC was assessed by using the Ulcerative Colitis Disease Activity Index (UCDAI) and Mayo endoscopic score.
Results: In patients with active UC the mean values of FC were 373.8 +/- 146.3 μg/g, significantly higher than those in the inactive UC (mean values 36.04 +/- 13.25 μg/g), and in IBS (42.9 +/- 16.00 μg/g). In univariate regression analysis, elevated FC levels strongly correlated with pancolitis (p=0.0001), UCDAI and Mayo scores (p=0.0001), and elevated CRP levels. In multivariate regression model, FC was positively associated with severe pancolitis, and elevated CRP. The optimal cutoff value of FC for the prediction of severe pancolitis (Mayo score˃ 3) was 540 μg/g. We obtained 71.4% sensitivity (CI95%: 41.95-91.6) and 96.1% specificity (CI95%: 89.2 -99.2) of FC in assessing the severity of inflammation in UC patients.
Conclusion: FC is a promising marker that can be used in clinical practice to select patients with organic intestinal disorders, compared with those with functional disorders. It also correlates very well with the extent of lesions and the severity of clinical symptoms in UC, with increased sensitivity and specificity.
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Marlicz W, Skonieczna-Żydecka K, Dabos KJ, Łoniewski I, Koulaouzidis A. Emerging concepts in non-invasive monitoring of Crohn's disease. Therap Adv Gastroenterol 2018; 11:1756284818769076. [PMID: 29707039 PMCID: PMC5912292 DOI: 10.1177/1756284818769076] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is an umbrella term for Crohn's disease (CD) and ulcerative colitis (UC). In light of evolving epidemiology of CD, its clinical management is still complex and remains a challenge for contemporary physicians. With the advent of new diagnostic and treatment paradigms, there is a growing need for new biomarkers to guide decision-making, differential diagnosis, disease activity monitoring, as well as prognosis. However, both clinical and endoscopic scoring systems, widely utilized for disease monitoring and prognosis, have drawbacks and limitations. In recent years, biochemical peptides have become available for IBD monitoring and more frequently used as surrogate markers of gut inflammation. Emerging concepts that revolve around molecular, stem cell, epigenetic, microbial or metabolomic pathways associated with vascular and epithelial gut barrier could lead to development of new CD biomarkers. Measurement of cell-derived microvesicles (MVs) in the blood of IBD patients is another emerging concept helpful in future disease management. In this review, we discuss novel concepts of non-invasive biomarkers, which may become useful in monitoring of CD activity and prognosis. We discuss metabolomics as a new powerful tool for clinicians to guide differential IBD diagnosis. In the coming years, new developments of prognostic tools are expected, aiming for breakthroughs in the management of patients with CD.
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Affiliation(s)
- Wojciech Marlicz
- Department of Gastroenterology, Pomeranian Medical University, Unii Lubelskiej 1, 71-252 Szczecin, Poland
| | | | | | - Igor Łoniewski
- Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Szczecin, Poland
- Sanprobi Sp. z o.o. Sp. K., Szczecin, Poland
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Teng X, Gao C, Sun M, Wu J. Clinical significance of fecal calprotectin for the early diagnosis of abdominal type of Henoch-Schonlein purpura in children. Clin Rheumatol 2017; 37:1667-1673. [PMID: 29018973 DOI: 10.1007/s10067-017-3864-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Revised: 09/20/2017] [Accepted: 10/01/2017] [Indexed: 12/16/2022]
Abstract
The objective of this study is to explore the value of fecal calprotectin (FC) for early screening of the abdominal type of Henoch-Schonlein purpura (AHSP) in children. The study cohort included 40 children with AHSP treated at Shengjing Hospital of China Medical University from November 2014 to November 2015, and 40 children hospitalized in the Division of Pediatric Orthopedics in the corresponding period were selected as a control group. Fresh fecal samples were collected in the acute phase of the first visit (FC1), 3 days after treatment (FC2), and 7 days after treatment (FC3) from the AHSP group and the control group. Calprotectin levels in the fecal samples were measured using an enzyme-linked immunosorbent assay. At the same time, gastrointestinal performance and the laboratory examination indicators white blood cell (WBC) count and C-reactive protein (CRP) level were recorded. The median levels of FC1 (3053 μg/g) and FC2 (2778.3 μg/g) were higher than in the control group (102.5 μg/g), with significant differences among the three groups (p < 0.001). FC levels gradually decreased in remission, and the level of FC3 on day 7 was close to that of the control samples (p > 0.05). When the optimal cut-off was 264.5 μg/g, the area under the receiver operating characteristic (ROC) curve of FC for diagnosis of AHSP was 0.961 with a corresponding sensitivity and specificity of 93.1 and 87.5%, respectively. The levels of FC in children with AHSP were positively correlated with WBC count (r s = 0.688) and CRP value (r s = 0.513). The area under the ROC curve of WBC count for screening AHSP was 0.785 when the optimal cut-off value was 11.1 × 109/L with a corresponding sensitivity and specificity of 81.5 and 62.5%, respectively. The area under the ROC curve of CRP was 0.963 when the optimal cut-off value was 5.72 mg/dL with a corresponding sensitivity and specificity of 88.9 and 100%, respectively. Comparisons of FC, WBC count, and CRP level as diagnostic indicators of AHSP showed that the sensitivity of FC was higher than that of the WBC count and CRP level, and its diagnostic value was better than that of the WBC count. The levels of FC began to increase in the early stages of AHSP, showing a decreasing tendency in remission and tending to be within a normal range after a week or so. For the early diagnosis of AHSP, FC with a cut-off level of 264.5 μg/g has good sensitivity and specificity. The sensitivity of FC is better than that of the traditional inflammation indicators CRP and WBC count, and its diagnostic performance is better than WBC count; FC can be suitable as a new marker for the early diagnosis of AHSP.
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Affiliation(s)
- Xu Teng
- Department of Pediatric Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China
| | - Cuiyun Gao
- Department of Pediatric, Central Hospital Affiliated To ShengYang Medical College, Shenyang, Liaoning, 110004, China
| | - Mei Sun
- Department of Pediatric Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China
| | - Jie Wu
- Department of Pediatric Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.
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