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Nakamura N, Honzawa Y, Ito Y, Sano Y, Yagi N, Kobayashi S, Aoi M, Tomiyama T, Tahara T, Fukata N, Fukui T, Naganuma M. Leucine-rich alpha-2 glycoprotein is useful in predicting clinical relapse in patients with Crohn's disease during biological remission. Intest Res 2025; 23:170-181. [PMID: 39155217 DOI: 10.5217/ir.2024.00042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 06/11/2024] [Indexed: 08/23/2024] Open
Abstract
BACKGROUND/AIMS Serum leucine-rich alpha-2 glycoprotein (LRG) is a potential biomarker of Crohn's disease (CD). This study aimed to evaluate the usefulness of LRG in predicting clinical relapse in patients in remission with CD. METHODS This retrospective observational study assessed the relationships among patient-reported outcome (PRO2), LRG, and other blood markers. The influence of LRG on clinical relapse was assessed in patients in remission with CD. RESULTS Data of 94 patients tested for LRG between January 2021 and May 2023 were collected. LRG level did not correlate with PRO2 score (ρ = 0.06); however, it strongly correlated with C-reactive protein (CRP) level (r=0.79) and serum albumin level (r=-0.70). Among 69 patients in clinical remission, relapse occurred in 22 patients (31.9%). In the context of predicting relapse, LRG showed the highest area under the curve, followed by CRP level, platelet count, and albumin level. Multivariate analysis revealed that only LRG (P= 0.02) was an independent factor for predicting clinical remission. The cumulative non-relapse rate was significantly higher in patients with LRG < 13.8 μg/mL than in patients in remission with LRG ≥ 13.8 μg/mL and normal CRP level (P= 0.002) or normal albumin level (P= 0.001). Cumulative non-relapse rate was also higher in patients with LRG < 13.8 μg/mL compared to those with LRG ≥ 13.8 μg/mL in patients with L3 or B2+B3 of Montreal calcification. CONCLUSIONS LRG is useful in predicting clinical relapse in patients with CD during biological remission. LRG is a useful biomarker for predicting prognosis, even in patients with intestinal stenosis, or previous/present fistulas.
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Affiliation(s)
- Naohiro Nakamura
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Yusuke Honzawa
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Yuka Ito
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Yasuki Sano
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Naoto Yagi
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Sanshiro Kobayashi
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Mamiko Aoi
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Takashi Tomiyama
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Tomomitsu Tahara
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Norimasa Fukata
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Toshiro Fukui
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Makoto Naganuma
- Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
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Omede M, Itam-Eyo A, Park A, Ikobah J, Ibrahim MK, Chukwudike E, Ali-Ibrahim A, Lydston M, Asombang AW, Ananthakrishnan AN. Epidemiology, Natural History, and Treatment of Inflammatory Bowel Disease in Africa: A Scoping Review. Clin Gastroenterol Hepatol 2025:S1542-3565(25)00197-1. [PMID: 40090434 DOI: 10.1016/j.cgh.2024.12.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 12/17/2024] [Accepted: 12/23/2024] [Indexed: 03/18/2025]
Abstract
BACKGROUND & AIMS Inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are global diseases. There is a paucity of knowledge about the burden and epidemiology of IBD in Africa. We performed a scoping review of the published literature on IBD in Africa to identify burden, risk factors, and outcomes as well as knowledge gaps. METHODS A comprehensive search was conducted in MEDLINE, Embase, Web of Science, AIM, Africa Wide, Cochrane, and ClinicalTrials.gov in November 2024. Studies were screened and selected based on predefined inclusion criteria. Data extraction was conducted using Covidence. Literature was summarized focusing on the incidence and prevalence, environmental factors, diagnosis, outcomes, and management of IBD. RESULTS Of 6896 references identified, a total of 268 studies met inclusion criteria. This included data from 21,089 patients with IBD (10,426 Crohn's disease; 7956 ulcerative colitis; 329 unspecified IBD; 2378 uncategorized IBD). There were few studies examining temporal incidence of IBD; in the sparse available data, a similar increase was notable as seen in the West. Studies of genetics and environment revealed many shared findings from known associations from Western cohorts (such as environmental hygiene) but highlight some differences as well. Use of biologic or advanced therapy was sparse. CONCLUSION We identified a paucity of publications regarding the risk factors, burden, and outcomes of IBD in Africa. There were few prospective studies and regional variations in representation. There is a need for more prospective data to inform our knowledge and management strategies accurately.
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Affiliation(s)
- Mmeyeneabasi Omede
- Division of Pediatric Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Asa Itam-Eyo
- Department of Internal Medicine, University of Calabar Teaching Hospital, Calabar, Nigeria
| | | | - Joanah Ikobah
- Department of Paediatrics, University of Calabar Teaching Hospital, Calabar, Nigeria
| | - Maryam K Ibrahim
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Evaristus Chukwudike
- Department of Internal Medicine, University of Calabar Teaching Hospital, Calabar, Nigeria
| | - Awab Ali-Ibrahim
- Division of Pediatric Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Melis Lydston
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Akwi W Asombang
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
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3
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Sousa MI, Dias E, Andrade P, Macedo G. Fecal calprotectin as an inflammatory biomarker in small bowel Crohn disease. Porto Biomed J 2024; 9:263. [PMID: 39132513 PMCID: PMC11309623 DOI: 10.1097/j.pbj.0000000000000263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 07/08/2024] [Accepted: 07/14/2024] [Indexed: 08/13/2024] Open
Abstract
Background Small bowel capsule endoscopy (SBCE) is an essential tool for evaluation of small bowel (SB) Crohn disease (CD). Fecal calprotectin (FC) represents an important biomarker of intestinal inflammation, widely used in ulcerative colitis and CD. Our aim was to evaluate the role of FC for diagnosing inflammatory activity in patients with isolated SB CD and how it correlates with SBCE findings. Methods This is a retrospective study conducted in a tertiary inflammatory bowel disease referral center that included patients with SB CD who underwent SBCE between January 2017 and February 2023. FC value was obtained from the closest stool examination to SBCE. Results One hundred ninety-six patients were included: 123 were women (63%) with a mean age of 44.2 years. In the SBCE, 127 (65%) patients had a Lewis Score ≥135 and, among the 94 patients with FC >200 μg/g, 23 had LS <135, 36 had LS between 135 and 790, and 35 had LS ≥790. FC levels were predictive of endoscopic lesions in SBCE, with significant correlation between FC level and total LS (Pearson correlation coefficient 0.43, P<.001). The sensitivity and specificity were calculated for each cut-off value being respectively 78% and 45% for FC = 100 μg/g, 69% and 59% for FC = 150 μg/g and 67% and 67% for FC = 200 μg/g. Conclusion FC showed moderate correlation with endoscopic findings in SBCE in SB CD. It is, therefore, a reasonable marker for predicting significant inflammatory lesions in SBCE; however, none of the cut-off had a high sensitivity or specificity.
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Affiliation(s)
- Maria I. Sousa
- Gastroenterology Department, Centro Hospitalar Universitário de São João, Porto, Portugal
- Faculty of Medicine, University of Porto, Porto, Portugal
| | - Emanuel Dias
- Gastroenterology Department, Centro Hospitalar Universitário de São João, Porto, Portugal
| | - Patrícia Andrade
- Gastroenterology Department, Centro Hospitalar Universitário de São João, Porto, Portugal
| | - Guilherme Macedo
- Gastroenterology Department, Centro Hospitalar Universitário de São João, Porto, Portugal
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Clough J, Colwill M, Poullis A, Pollok R, Patel K, Honap S. Biomarkers in inflammatory bowel disease: a practical guide. Therap Adv Gastroenterol 2024; 17:17562848241251600. [PMID: 38737913 PMCID: PMC11085009 DOI: 10.1177/17562848241251600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 04/12/2024] [Indexed: 05/14/2024] Open
Abstract
Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), is a costly condition in terms of morbidity and healthcare utilization, with an increasing prevalence now approaching 1% in the Western world. Endoscopic assessment of IBD remains the gold standard for diagnosis, evaluation of treatment response and determination of post-operative recurrence, but is expensive and invasive. Biomarkers can facilitate non-invasive disease assessment, with C-reactive protein and faecal calprotectin as the most widely available biomarkers in current clinical practice. This narrative review summarizes the evidence for their use in both UC and CD and offers practical guidance for healthcare providers taking into account the limitations of biomarker interpretation. We present evidence for the future use of novel biomarkers in IBD and discuss how biomarker discovery could deliver the goal of precision medicine in IBD.
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Affiliation(s)
- Jennie Clough
- St George’s University Hospitals NHS Foundation Trust, London, UK
- School of Immunology and Microbial Sciences, King’s College London, London, UK
| | - Michael Colwill
- St George’s University Hospitals NHS Foundation Trust, London, UK
| | - Andrew Poullis
- St George’s University Hospitals NHS Foundation Trust, London, UK
| | - Richard Pollok
- St George’s University Hospital NHS Foundation Trust
- Institute of Infection and Immunity, St George’s University, London, UK
| | - Kamal Patel
- St George’s University Hospitals NHS Foundation Trust, London, UK
| | - Sailish Honap
- St George’s University Hospitals NHS Foundation Trust, London, UK
- School of Immunology and Microbial Sciences, King’s College London, London, UK
- INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France
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5
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Carrillo-Palau M, Vera-Santana B, Morant-Domínguez A, Hernández-Camba A, Ramos L, Alonso-Abreu I, Hernández Álvarez-Buylla N, Arranz L, Vela M, Hernández-Guerra M, Gómez-Moreno C, González-Gay MÁ, Ferraz-Amaro I. Hematological Composite Scores in Patients with Inflammatory Bowel Disease. J Clin Med 2023; 12:7248. [PMID: 38068300 PMCID: PMC10706900 DOI: 10.3390/jcm12237248] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 11/19/2023] [Accepted: 11/21/2023] [Indexed: 01/04/2025] Open
Abstract
The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and the systemic immune-inflammatory index (SIRI, neutrophils × monocytes/lymphocytes) have been identified as potential inflammatory biomarkers. In this work we aimed to analyze whether the hematological composite scores differ between inflammatory bowel disease (IBD) patients and healthy controls, and if they are related to disease activity. A total of 197 IBD patients-130 Crohn's (CD) disease and 67 ulcerative colitis (UC)-and 208 age- and sex-matched healthy controls were enrolled. C-reactive protein and fecal calprotectin were assessed. Multivariable linear regression analysis was executed. After adjustment, NLR and PLR, but not SIRI and MLR, were significantly higher in IBD patients compared to controls. C-reactive protein and SIRI and NLR were correlated in IBD patients. However, fecal calprotectin was not related to any of these blood scores. Furthermore, disease activity parameters were not associated with any of the blood composite scores in both CD and UC patients. In conclusion, NLR and PLR, but not SIRI and MLR, are independently higher in IBD patients compared to controls. However, the four hematological scores are not related to disease activity in either CD or UC patients. Based on these results, blood-based inflammatory scores may not serve as subrogated biomarkers of disease activity in IBD.
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Affiliation(s)
- Marta Carrillo-Palau
- Division of Gastroenterology, Hospital Universitario de Canarias, 38320 Tenerife, Spain; (M.C.-P.); (B.V.-S.); (A.M.-D.); (L.R.); (I.A.-A.); (N.H.Á.-B.); (M.H.-G.)
| | - Belén Vera-Santana
- Division of Gastroenterology, Hospital Universitario de Canarias, 38320 Tenerife, Spain; (M.C.-P.); (B.V.-S.); (A.M.-D.); (L.R.); (I.A.-A.); (N.H.Á.-B.); (M.H.-G.)
| | - Andrea Morant-Domínguez
- Division of Gastroenterology, Hospital Universitario de Canarias, 38320 Tenerife, Spain; (M.C.-P.); (B.V.-S.); (A.M.-D.); (L.R.); (I.A.-A.); (N.H.Á.-B.); (M.H.-G.)
| | - Alejandro Hernández-Camba
- Division of Gastroenterology, Hospital Universitario de Nuestra Señora de la Candelaria, 38010 Tenerife, Spain; (A.H.-C.); (L.A.); (M.V.)
| | - Laura Ramos
- Division of Gastroenterology, Hospital Universitario de Canarias, 38320 Tenerife, Spain; (M.C.-P.); (B.V.-S.); (A.M.-D.); (L.R.); (I.A.-A.); (N.H.Á.-B.); (M.H.-G.)
| | - Inmaculada Alonso-Abreu
- Division of Gastroenterology, Hospital Universitario de Canarias, 38320 Tenerife, Spain; (M.C.-P.); (B.V.-S.); (A.M.-D.); (L.R.); (I.A.-A.); (N.H.Á.-B.); (M.H.-G.)
| | - Noemi Hernández Álvarez-Buylla
- Division of Gastroenterology, Hospital Universitario de Canarias, 38320 Tenerife, Spain; (M.C.-P.); (B.V.-S.); (A.M.-D.); (L.R.); (I.A.-A.); (N.H.Á.-B.); (M.H.-G.)
| | - Laura Arranz
- Division of Gastroenterology, Hospital Universitario de Nuestra Señora de la Candelaria, 38010 Tenerife, Spain; (A.H.-C.); (L.A.); (M.V.)
| | - Milagros Vela
- Division of Gastroenterology, Hospital Universitario de Nuestra Señora de la Candelaria, 38010 Tenerife, Spain; (A.H.-C.); (L.A.); (M.V.)
| | - Manuel Hernández-Guerra
- Division of Gastroenterology, Hospital Universitario de Canarias, 38320 Tenerife, Spain; (M.C.-P.); (B.V.-S.); (A.M.-D.); (L.R.); (I.A.-A.); (N.H.Á.-B.); (M.H.-G.)
| | - Cristina Gómez-Moreno
- Fundación Jiménez Díaz School of Nursing of Madrid, Autonomous University of Madrid, 28040 Madrid, Spain;
| | - Miguel Á. González-Gay
- Division of Rheumatology, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, 28040 Madrid, Spain
- Department of Medicine, University of Cantabria, 39005 Santander, Spain
| | - Iván Ferraz-Amaro
- Division of Rheumatology, Hospital Universitario de Canarias, 38320 Tenerife, Spain
- Department of Internal Medicine, Universidad de La Laguna (ULL), 38200 Tenerife, Spain
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Kapel N, Ouni H, Benahmed NA, Barbot-Trystram L. Fecal Calprotectin for the Diagnosis and Management of Inflammatory Bowel Diseases. Clin Transl Gastroenterol 2023; 14:e00617. [PMID: 37440723 PMCID: PMC10522095 DOI: 10.14309/ctg.0000000000000617] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 06/13/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
Calprotectin is a heterodimeric calcium- and zinc-binding protein mainly derived from the cytoplasm of neutrophils that has direct antimicrobial functions and a role in the regulation of the innate immune response. It can be found in various biological compartments, in particular, the stool, with concentrations related to the level of mucosal inflammation. The measurement of fecal calprotectin has thus been recognized as a useful surrogate marker to distinguish patients with inflammatory bowel disease from those with irritable bowel syndrome. Moreover, it allows the monitoring of intestinal inflammation with a high negative predictive value, making it possible to exclude the diagnosis of inflammatory bowel disease for symptomatic patients. It also shows high sensitivity for the identification of patients requiring additional examinations for diagnosis, such as colonoscopy, and the evaluation of therapeutic responses, providing evidence of relapse or mucosal healing, which can lead to the intensification or reduction of treatment. As calprotectin levels are a measure of mucosal inflammation, high fecal concentrations are also found in other diseases with an inflammatory component, such as infectious enteritis or colorectal cancer. Interpretation of the concentration must therefore always take into account the clinical history and symptoms specific to each patient.
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Affiliation(s)
- Nathalie Kapel
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
- INSERM UMR-S1139, Faculté de Pharmacie, Université de Paris Cité, Paris, France
| | - Hamza Ouni
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
| | - Nacer Adam Benahmed
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
| | - Laurence Barbot-Trystram
- Laboratoire de Coprologie Fonctionnelle, Laboratoire de Biologie Médicale de Référence «Exploration Biochimique des Selles (Phénotype)», AP–HP, Hôpital Universitaire Pitié Salpêtrière-Charles Foix, Paris, France
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7
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Ostermann L, Seeliger B, David S, Flasche C, Maus R, Reinboth MS, Christmann M, Neumann K, Brand K, Seltmann S, Bühling F, Paton JC, Roth J, Vogl T, Viemann D, Welte T, Maus UA. S100A9 is indispensable for survival of pneumococcal pneumonia in mice. PLoS Pathog 2023; 19:e1011493. [PMID: 37467233 DOI: 10.1371/journal.ppat.1011493] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 06/18/2023] [Indexed: 07/21/2023] Open
Abstract
S100A8/A9 has important immunomodulatory roles in antibacterial defense, but its relevance in focal pneumonia caused by Streptococcus pneumoniae (S. pneumoniae) is understudied. We show that S100A9 was significantly increased in BAL fluids of patients with bacterial but not viral pneumonia and correlated with procalcitonin and sequential organ failure assessment scores. Mice deficient in S100A9 exhibited drastically elevated Zn2+ levels in lungs, which led to bacterial outgrowth and significantly reduced survival. In addition, reduced survival of S100A9 KO mice was characterized by excessive release of neutrophil elastase, which resulted in degradation of opsonophagocytically important collectins surfactant proteins A and D. All of these features were attenuated in S. pneumoniae-challenged chimeric WT→S100A9 KO mice. Similarly, therapy of S. pneumoniae-infected S100A9 KO mice with a mutant S100A8/A9 protein showing increased half-life significantly decreased lung bacterial loads and lung injury. Collectively, S100A9 controls central antibacterial immune mechanisms of the lung with essential relevance to survival of pneumococcal pneumonia. Moreover, S100A9 appears to be a promising biomarker to distinguish patients with bacterial from those with viral pneumonia. Trial registration: Clinical Trials register (DRKS00000620).
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Affiliation(s)
- Lena Ostermann
- Division of Experimental Pneumology, Hannover Medical School, Hannover, Germany
| | - Benjamin Seeliger
- Clinic for Pneumology, Hannover Medical School, Hannover, Germany
- German Center for Lung Research, Hannover, Germany
| | - Sascha David
- Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland
| | - Carolin Flasche
- Division of Experimental Pneumology, Hannover Medical School, Hannover, Germany
| | - Regina Maus
- Division of Experimental Pneumology, Hannover Medical School, Hannover, Germany
| | - Marieke S Reinboth
- Division of Experimental Pneumology, Hannover Medical School, Hannover, Germany
| | - Martin Christmann
- Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany
| | - Konstantin Neumann
- Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany
| | - Korbinian Brand
- Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany
| | | | - Frank Bühling
- Labopart Medical Laboratories, Dresden and Chemnitz, Germany
| | - James C Paton
- Research Centre for Infectious Diseases, Department of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia
| | - Johannes Roth
- Institute of Immunology, University of Münster, Münster, Germany
| | - Thomas Vogl
- Institute of Immunology, University of Münster, Münster, Germany
| | - Dorothee Viemann
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
- Translational Pediatrics, Department of Pediatrics, University Hospital Würzburg, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
- Center for Infection Research, University Würzburg, Germany
| | - Tobias Welte
- Clinic for Pneumology, Hannover Medical School, Hannover, Germany
- German Center for Lung Research, Hannover, Germany
| | - Ulrich A Maus
- Division of Experimental Pneumology, Hannover Medical School, Hannover, Germany
- German Center for Lung Research, Hannover, Germany
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8
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Shi JT, Chen N, Xu J, Goyal H, Wu ZQ, Zhang JX, Xu HG. Diagnostic Accuracy of Fecal Calprotectin for Predicting Relapse in Inflammatory Bowel Disease: A Meta-Analysis. J Clin Med 2023; 12:1206. [PMID: 36769850 PMCID: PMC9917450 DOI: 10.3390/jcm12031206] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 01/28/2023] [Accepted: 01/31/2023] [Indexed: 02/05/2023] Open
Abstract
Fecal calprotectin (FC) levels correlate with the disease activity of inflammatory bowel diseases (IBD); however, the utility of FC in predicting IBD relapse remains to be determined. We aim to evaluate the efficacy of fecal calprotectin in predicting the relapse of inflammatory bowel disease. We searched Pubmed (MEDLINE), Embase, Web of Science, and the Cochrane library databases up to 7 July 2021. Our study estimated the pooled sensitivity and specificity, summary receiver operating characteristic (SROC) curve, and the optimal cut-off value for predicting IBD relapse using a multiple threshold model. A total of 24 prospective studies were included in the meta-analysis. The optimal FC cut-off value was 152 μg/g. The pooled sensitivity and specificity of FC was 0.720 (0.528 to 0.856) and 0.740 (0.618 to 0.834), respectively. FC is a useful, non-invasive, and inexpensive biomarker for the early prediction of IBD relapse. An FC value of 152 μg/g is an ideal threshold to identify patients with a high relapse probability.
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Affiliation(s)
- Jin-Tong Shi
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Nuo Chen
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Jia Xu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Hemant Goyal
- Division of Gastroenterology, Hepatology & Nutrition, University of Texas Health Sciences Center, Houston, TX 77030, USA
| | - Zhi-Qi Wu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Jie-Xin Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Hua-Guo Xu
- Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
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9
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Relationship between the Levels of Calprotectin and Soluble Receptor for Advanced Glycation End Products with Abdominal Aortic Aneurysm Diameter: A Preliminary Clinical Trial. J Clin Med 2022; 11:jcm11185448. [PMID: 36143093 PMCID: PMC9501553 DOI: 10.3390/jcm11185448] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/06/2022] [Accepted: 09/13/2022] [Indexed: 11/19/2022] Open
Abstract
An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta greater than 50% of the diameter of a healthy aorta. Previous experimental studies confirm the effect of calprotectin (CAL) on the onset of arterial pathology. It has been suggested that low levels of soluble receptors for advanced glycation end products (RAGEs) increase levels of cytokines that lead to the inhibition of matrix metalloproteinases (MMPs), affecting AAA formation. This study aimed to analyze the correlation of levels of RAGE and CAL with AAA diameter. A group of 32 patients aged 50−75 with diagnosed AAA was enrolled in the study. This group of patients was further divided into three subgroups based on AAA diameter: (1) <4.5 cm, (2) 4.5−5.5 cm, (3) >5.5 cm. Peripheral blood was drawn from all participants on admission to measure the serum CAL and RAGE levels. An enumeration survey was performed three months after AAA surgical treatment. CAL and RAGE plasma levels were measured with the enzyme-linked immunosorbent assay (ELISA). The median CAL levels were 2273.0 ng/mL before and 1217.0 ng/mL after treatment. There was a statistically significant decrease in CAL levels following the surgical treatment (p = 0.003). The correlation analysis between CAL levels and RAGE levels before and after surgical treatment showed no statistically significant correlations. In addition, there were no statistically significant correlations between CAL and RAGE levels with AAA size. In conclusion, CAL levels appear to be a significant marker in patients with AAA. There is an almost twofold decrease in CAL levels after AAA excision.
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Lee YJ, Park JH. Fecal Calprotectin Assay at an Early Stage of Treatment Can Be Used as a Surrogate Marker to Predict Clinical Remission and Mucosal Healing in Pediatric Crohn's Disease. Pediatr Gastroenterol Hepatol Nutr 2022; 25:396-405. [PMID: 36148291 PMCID: PMC9482829 DOI: 10.5223/pghn.2022.25.5.396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 01/05/2022] [Accepted: 07/28/2022] [Indexed: 11/14/2022] Open
Abstract
PURPOSE This study evaluated the predictive role of fecal calprotectin (FC) measured at an early stage of treatment for monitoring clinical remission (CR) after six months and endoscopic remission (ER) after one year of treatment in pediatric Crohn's disease (CD). METHODS This retrospective study included 45 patients who simultaneously underwent ileocolonoscopy and FC testing during follow-up. FC levels were measured before and after six weeks of treatment. CR was assessed after six months of treatment using Pediatric Crohn' s Disease Activity Index and acute-phase reactants. ER was assessed after one year using the Simple Endoscopic Score for Crohn's Disease. RESULTS Twenty-nine (64.4%) patients used oral prednisolone for remission induction and 16 (35.6%) patients used anti-tumor necrosis factor-alpha. Thirty (66.7%) patients achieved CR, while 24 (53.3%) achieved ER. The FC level measured after six weeks of treatment could predict CR (χ2=9.15, p=0.0025) and ER (χ2=12.31, p=0.0004). The δFC could predict CR (χ2=7.91, p=0.0049), but not ER (χ2=1.85, p=0.1738). With a threshold of ≤950.4 µg/g, FC at week six could predict CR with 76.7% sensitivity and 73.3% specificity. The area under the curve (AUC) was 0.769 (standard error 0.0773, p=0.0005). The same threshold predicted ER with 87.5% sensitivity and 71.4% specificity. The AUC was 0.774 (standard error 0.074, p=0.0002). CONCLUSION FC assay at an early stage of treatment can be used as a surrogate marker to predict CR and mucosal healing in pediatric CD.
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Affiliation(s)
- Yeoun Joo Lee
- Department of Pediatrics, Pusan National University School of Medicine, Yangsan, Korea
| | - Jae Hong Park
- Department of Pediatrics, Pusan National University School of Medicine, Yangsan, Korea
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11
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Cao Y, Dai Y, Zhang L, Wang D, Hu W, Yu Q, Wang X, Yu P, Liu W, Ping Y, Sun T, Sang Y, Liu Z, Chen Y, Tao Z. Combined Use of Fecal Biomarkers in Inflammatory Bowel Diseases: Oncostatin M and Calprotectin. J Inflamm Res 2021; 14:6409-6419. [PMID: 34880643 PMCID: PMC8647726 DOI: 10.2147/jir.s342846] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/20/2021] [Indexed: 12/12/2022] Open
Abstract
Background Fecal biomarkers have emerged as one of the most useful tools for clinical management of inflammatory bowel disease (IBD). Oncostatin M (OSM), like fecal calprotectin (FC), is highly expressed in the inflamed intestinal mucosa which may have potential usefulness. We aimed to evaluate the additional utility of these two fecal biomarkers for IBD diagnosis, activity, and prediction of infliximab response over FC alone. Methods In group 1, 236 IBD patients (145 Crohn’s disease, 91 ulcerative colitis), 50 disease controls, and 32 healthy controls were recruited for IBD diagnosis and activity. In group 2, baseline stool samples were collected from 62 patients to predict infliximab response at week 28 and 52. The performance of fecal biomarkers for IBD management was assessed by the area under the receiver operating characteristic curve (AUC). Results Fecal OSM and FC levels were increased in IBD patients and were positively correlated with clinical and endoscopic activity. Their combination showed a better ability for disease diagnosis (AUC = 0.93) and slightly improved the capability to identify mucosal healing (AUC = 0.923). Baseline OSM and FC levels were elevated in non-responders at week 28 and 52. The AUCs of OSM, FC, and their combination to predict therapeutic response were 0.763, 0.834, and 0.859 at week 28, 0.638, 0.661, and 0.704 at week 52, respectively. Combined use of fecal and blood biomarkers improved predictive accuracy with an AUC of 0.919 at week 28 and 0.887 at week 52. Conclusion In addition to FC, OSM is a novel fecal biomarker, and their combination is more beneficial for disease diagnosis and prediction of infliximab response but not for disease activity in IBD patients. Further larger-scale studies are required to confirm our findings.
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Affiliation(s)
- Ying Cao
- Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People's Republic of China
| | - Yibei Dai
- Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People's Republic of China
| | - Lingyu Zhang
- Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People's Republic of China
| | - Danhua Wang
- Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People's Republic of China
| | - Wen Hu
- National Clinical Research Center for Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, People's Republic of China
| | - Qiao Yu
- Center for Inflammatory Bowel Diseases, Department of Gastroenterology, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People's Republic of China
| | - Xuchu Wang
- Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People's Republic of China
| | - Pan Yu
- Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People's Republic of China
| | - Weiwei Liu
- Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People's Republic of China
| | - Ying Ping
- Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People's Republic of China
| | - Tao Sun
- Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People's Republic of China
| | - Yiwen Sang
- Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People's Republic of China
| | - Zhenping Liu
- Department of Laboratory Medicine, the First People's Hospital of Yuhang District, Hangzhou, People's Republic of China
| | - Yan Chen
- Center for Inflammatory Bowel Diseases, Department of Gastroenterology, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People's Republic of China
| | - Zhihua Tao
- Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People's Republic of China
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12
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Jung ES, Lee SP, Kae SH, Kim JH, Kim HS, Jang HJ. Diagnostic Accuracy of Fecal Calprotectin for the Detection of Small Bowel Crohn's Disease through Capsule Endoscopy: An Updated Meta-Analysis and Systematic Review. Gut Liver 2021; 15:732-741. [PMID: 33361549 PMCID: PMC8444097 DOI: 10.5009/gnl20249] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 09/21/2020] [Accepted: 10/27/2020] [Indexed: 12/13/2022] Open
Abstract
Background/Aims The diagnosis of small bowel Crohn's disease with negative ileocolonoscopic findings has been challenging. Fecal calprotectin (FC) has been used to detect colonic inflammation, but its efficacy for detecting small bowel inflammation is less established. We performed an updated meta-analysis to evaluate the diagnostic accuracy of FC to detect active small bowel inflammation observed during capsule endoscopy. Methods We conducted a systematic literature search for studies that evaluated the correlation between small bowel inflammation and FC in patients with suspected/established Crohn's disease. We calculated the pooled sensitivity, specificity, and diagnostic odds ratios (DORs) and constructed hierarchical summary receiver operating characteristic curves for FC cutoffs of 50, 100, and 200 μg/g. Results Fourteen studies were eligible for the final analysis. The DORs of all FC cutoffs were significant. The highest DOR was observed at 100 μg/g (sensitivity, 0.73; specificity, 0.73; and DOR, 7.89) and was suggested as the optimal diagnostic cutoff. If we analyzed only studies that included patients with suspected Crohn's disease, the DOR was 8.96. If we analyzed only studies that included patients with a Lewis score ≥135 as a diagnostic criterion for active disease, the DOR was 10.90. Conclusions FC has significant diagnostic accuracy for detecting small bowel inflammation, and an FC cutoff of 100 μg/g can be used as a tool to screen for small bowel Crohn's disease.
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Affiliation(s)
- Eun Suk Jung
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Sang Pyo Lee
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Sea Hyub Kae
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
| | - Jung Han Kim
- Division of Hematology-Oncology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Hyeong Su Kim
- Division of Hematology-Oncology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Hyun Joo Jang
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea
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13
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Hauzer W, Ferenc S, Rosińczuk J, Gnus J. The Role of Serum Calprotectin as a New Marker in Abdominal Aortic Aneurysms - A Preliminary Report. Curr Pharm Biotechnol 2021; 22:508-513. [PMID: 33208067 DOI: 10.2174/1389201021666201117095215] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 10/05/2020] [Accepted: 10/10/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Abdominal Aortic Aneurysm (AAA) remains a surgical challenge. There are many recognizable markers associated with the formation of AAA. Previous experiments carried out on animal models have shown a correlation between serum calprotectin and the occurrence of AAA. OBJECTIVE This study aimed to evaluate the level of calprotectin as a potential diagnostic biomarker in patients with diagnosed AAA. METHODS The study group consisted of 75 patients aged 35-75 years assigned to two groups: a control group (n=43) of healthy subjects without AAA and a study group (n=32) of patients with a diagnosed AAA. The first calprotectin test was performed upon patient admission to the hospital, and the second control test was performed after three months. The concentration of calprotectin in plasma was determined using the Immunoenzymatic Method (ELISA) with the commercially available Assaypro Kit (AssayMax™ Human Calprotectin ELISA Kit), as well as the sandwich method with polyclonal antibodies to human calprotectin and peroxidase enzyme. RESULTS & DISCUSSION Serum calprotectin levels in AAA patients were three times higher than in healthy subjects (p<0.05). A statistically significant twofold decrease in calprotectin concentration was observed after AAA surgery compared to the control group (p<0.05). CONCLUSION Calprotectin levels can be an important marker in the detection of AAA. In conclusion, AAA patients showed a threefold increase in serum calprotectin level and a twofold decrease in this marker after AAA surgery.
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Affiliation(s)
- Willy Hauzer
- Department of General and Vascular Surgery, Regional Specialist Hospital in Wroclaw, Wroclaw, Poland
| | - Stanisław Ferenc
- Department of General and Vascular Surgery, Regional Specialist Hospital in Wroclaw, Wroclaw, Poland
| | - Joanna Rosińczuk
- Department of Nervous System Diseases, Faculty of Health Sciences, Wroclaw Medical University, Wroclaw, Poland
| | - Jan Gnus
- Department of Physiotherapy, Faculty of Health Sciences, Wroclaw Medical University, Wroclaw, Poland
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14
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Liu F, Lee SA, Riordan SM, Zhang L, Zhu L. Global Studies of Using Fecal Biomarkers in Predicting Relapse in Inflammatory Bowel Disease. Front Med (Lausanne) 2020; 7:580803. [PMID: 33392214 PMCID: PMC7773777 DOI: 10.3389/fmed.2020.580803] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 12/01/2020] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract mainly comprising two forms including Crohn's disease (CD) and ulcerative colitis (UC). IBD is a lifelong relapsing remitting disease and relapses occur at random patterns which are unpredictable. Fecal biomarkers have been increasingly used to assess disease activity in IBD due to their positive correlations with intestinal inflammation. Recent studies have also assessed the use of fecal biomarkers in predicting relapse and post-operative recurrence. This review provides information from global studies of using fecal calprotectin, lactoferrin and S100A12 to predict relapse in IBD. Strategies for further studies and the use of these fecal biomarkers for personalized management in IBD are also discussed.
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Affiliation(s)
- Fang Liu
- Department of General Surgery and Central Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Seul A. Lee
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Stephen M. Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales, Sydney, NSW, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Lixin Zhu
- Department of General Surgery and Central Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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15
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Khaki-Khatibi F, Qujeq D, Kashifard M, Moein S, Maniati M, Vaghari-Tabari M. Calprotectin in inflammatory bowel disease. Clin Chim Acta 2020; 510:556-565. [PMID: 32818491 PMCID: PMC7431395 DOI: 10.1016/j.cca.2020.08.025] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/11/2020] [Accepted: 08/13/2020] [Indexed: 02/07/2023]
Abstract
The term IBD is usually used for referring to a group of inflammatory gastro-intestinal diseases (mainly Crohn's disease and ulcerative colitis). Accordingly, IBD arises as a result of inappropriate immune response to intestinal commensal organisms among genetically susceptible individuals. Performing colonoscopy and histopathologic evaluation on an inflamed bowel biopsy specimen are currently considered as gold standards for diagnosis and management of IBD. Correspondingly, these techniques are known to be invasive and costly. In recent decades, fecal calprotectin, as a biomarker, has received much attention for the diagnosis and non-invasive management of IBD. Up to now, many studies have investigated the efficacy of fecal calprotectin in the areas of IBD differentiation from IBS, prediction of endoscopic and histologic activities of IBD and prediction of disease recurrence. Although some of these studies have reported promising results, some others have shown significant limitations. Therefore, in this paper, we reviewed the most interesting ones of these studies after a brief discussion of the laboratory measurement of fecal calprotectin. Moreover, we attempted to provide an answer for the question of whether fecal-calprotectin could be considered as a potential surrogate marker for colonoscopy.
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Affiliation(s)
- Fatemeh Khaki-Khatibi
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Durdi Qujeq
- Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran,Department of Clinical Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Mehrdad Kashifard
- Department of Internal Medicine, Gastroenterology Division, Ayatollah Rouhani Hospital, Babol University of Medical Sciences, Babol, Iran
| | - Soheila Moein
- Department of Biochemistry, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Mahmood Maniati
- English Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mostafa Vaghari-Tabari
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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16
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Vernia F, Di Ruscio M, Stefanelli G, Viscido A, Frieri G, Latella G. Is fecal calprotectin an accurate marker in the management of Crohn's disease? J Gastroenterol Hepatol 2020; 35:390-400. [PMID: 31795013 DOI: 10.1111/jgh.14950] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 11/06/2019] [Accepted: 11/16/2019] [Indexed: 12/14/2022]
Abstract
Although lacking validated cutoff values, fecal calprotectin (FC), besides C-reactive protein, is considered the standard test for assessing disease activity in Crohn's disease (CD). The aim of the present review is to provide a general overview of the literature addressing the role of FC in the clinical and endoscopic assessment of disease activity in CD, seeking correlations with capsule endoscopy, response to therapy, prediction of relapse, and postoperative recurrence. A systematic search of the literature up to September 2019 was performed using Medline, Embase, and the Cochrane Library. Only papers written in English concerning FC in adult patients affected by CD were included. Pediatric studies, in vitro studies, animal studies, studies on blood/serum samples, and studies analyzing FC in ulcerative colitis or in both CD and ulcerative colitis were excluded. Out of 713 citations, 65 eligible studies were identified. FC showed high accuracy in the assessment of intestinal inflammation and response to therapy, in particular in colonic disease, thus proving a good surrogate marker for these aims. FC is useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence, for optimizing or downstage therapy. Unfortunately, FC performs less well in small bowel CD. FC is an effective fecal marker in the management of CD patients, optimizing the use of endoscopic procedures. Owing to its diagnostic accuracy, FC may represent a cornerstone of the "treat-to-target" management strategy of CD patients.
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Affiliation(s)
- Filippo Vernia
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Mirko Di Ruscio
- IBD Unit, IRCCS Ospedale Sacro Cuore - Don Calabria, Verona, Italy
| | - Gianpiero Stefanelli
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Angelo Viscido
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Giuseppe Frieri
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Giovanni Latella
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
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17
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Ma C, Battat R, Parker CE, Khanna R, Jairath V, Feagan BG. Update on C-reactive protein and fecal calprotectin: are they accurate measures of disease activity in Crohn's disease? Expert Rev Gastroenterol Hepatol 2019; 13:319-330. [PMID: 30791776 DOI: 10.1080/17474124.2019.1563481] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
'Treat-to-target' paradigms in Crohn's disease (CD) directed at suppressing intestinal inflammation require accurate and reliable measures of disease activity. Although endoscopy has traditionally been considered a gold standard, cost, complexity, resource limitations, and invasiveness are important limitations. Hence, substantial interest exists for non-invasive serum and fecal biomarkers, namely C-reactive protein (CRP) and fecal calprotectin (FC), in the diagnosis, monitoring, and treatment of CD. Areas covered: We review the evidence for using serum CRP and FC in distinguishing patients with CD from those with irritable bowel syndrome, categorizing disease activity among patients with an established diagnosis of CD, predicting the likelihood of treatment response, identifying asymptomatic patients in medically or surgically induced remission who are at risk for disease relapse, and as treatment targets. Expert commentary: Accurate interpretation of CRP and FC is dependent on several factors including the clinical context, the performance characteristics of the assay, the specified test cut-offs, and the pre-test probability of disease. Emerging evidence indicates that CRP and FC are valuable adjuncts for the management of CD in specific circumstances described in this review.
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Affiliation(s)
- Christopher Ma
- a Division of Gastroenterology and Hepatology , University of Calgary , Calgary , Alberta , Canada.,b Robarts Clinical Trials Inc ., London , Ontario , Canada
| | - Robert Battat
- b Robarts Clinical Trials Inc ., London , Ontario , Canada.,c Division of Gastroenterology , University of California San Diego , La Jolla , CA , USA
| | | | - Reena Khanna
- d Department of Medicine , Western University , London , Ontario , Canada
| | - Vipul Jairath
- b Robarts Clinical Trials Inc ., London , Ontario , Canada.,d Department of Medicine , Western University , London , Ontario , Canada.,e Department of Epidemiology and Biostatistics , Western University , London , Ontario , Canada
| | - Brian Gordon Feagan
- b Robarts Clinical Trials Inc ., London , Ontario , Canada.,d Department of Medicine , Western University , London , Ontario , Canada.,e Department of Epidemiology and Biostatistics , Western University , London , Ontario , Canada
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18
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Jeong SJ. The role of fecal calprotectin in pediatric disease. KOREAN JOURNAL OF PEDIATRICS 2019; 62:287-291. [PMID: 30999729 PMCID: PMC6702112 DOI: 10.3345/kjp.2019.00059] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 03/28/2019] [Indexed: 12/13/2022]
Abstract
Fecal calprotectin (FC) is a calcium- and zinc-binding protein of the S100 family, mainly expressed by neutrophils and released during inflammation. FC became an increasingly useful tool both for gastroenterologists and for general practitioners for distinguishing inflammatory bowel disease (IBD) from irritable bowel syndrome. Increasing evidences support the use of this biomarker for diagnosis, follow-up and evaluation of response to therapy of several pediatric gastrointestinal diseases, ranging from IBD to nonspecific colitis and necrotizing enterocolitis. This article summarizes the current literature on the use of FC in clinical practice.
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Affiliation(s)
- Su Jin Jeong
- Department of Pediatrics, Bundang CHA Medical Center, CHA University School of Medicine, Seongnam, Korea
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19
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Foster AJ, Smyth M, Lakhani A, Jung B, Brant RF, Jacobson K. Consecutive fecal calprotectin measurements for predicting relapse in pediatric Crohn’s disease patients. World J Gastroenterol 2019; 25:1266-1277. [PMID: 30886509 PMCID: PMC6421242 DOI: 10.3748/wjg.v25.i10.1266] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 01/16/2019] [Accepted: 01/18/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Asymptomatic children with Crohn’s disease (CD) require ongoing monitoring to ensure early recognition of a disease exacerbation.
AIM In a cohort of pediatric CD patients, we aimed to assess the utility of serial fecal calprotectin measurements to detect intestinal inflammatory activity and predict disease relapse.
METHODS In this prospective longitudinal cohort study, children with CD on infliximab therapy in clinical remission were included. Fecal calprotectin levels were assessed at baseline and at subsequent 2-5 visits. Clinical and biochemical disease activity were assessed using the Pediatric Crohn’s Disease Activity Index, C-reactive protein and erythrocyte sedimentation rate at baseline and at visits over the following 18 mo.
RESULTS 53 children were included and eighteen patients (34%) had a clinical disease relapse during the study. Baseline fecal calprotectin levels were higher in patients that developed symptomatic relapse [median (interquartile range), relapse 723 μg/g (283-1758) vs 244 μg/g (61-627), P = 0.02]. Fecal calprotectin levels > 250 μg/g demonstrated good predictive accuracy of a clinical flare within 3 mo (area under the receiver operator curve was 0.86, 95% confidence limits 0.781 to 0.937).
CONCLUSION Routine fecal calprotectin testing in children with CD in clinical remission is useful to predict relapse. Levels > 250 μg/g are a good predictor of relapse in the following 3 mo. This information is important to guide monitoring standards used in this population.
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Affiliation(s)
- Alice Jane Foster
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, BC V6H 3V4, Canada
- Pediatrics, B.C. Children’s Hospital Research Institute, Vancouver, BC V6H 3V4, Canada
- Pediatrics, British Columbia children’s Hospital, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
| | - Matthew Smyth
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, BC V6H 3V4, Canada
- Pediatrics, B.C. Children’s Hospital Research Institute, Vancouver, BC V6H 3V4, Canada
- Pediatrics, British Columbia children’s Hospital, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
| | - Alam Lakhani
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, BC V6H 3V4, Canada
- Pediatrics, B.C. Children’s Hospital Research Institute, Vancouver, BC V6H 3V4, Canada
- Pediatrics, British Columbia children’s Hospital, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
| | - Benjamin Jung
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, BC V6H 3V4, Canada
- Pediatrics, B.C. Children’s Hospital Research Institute, Vancouver, BC V6H 3V4, Canada
| | - Rollin F Brant
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, BC V6H 3V4, Canada
- Department of Statistics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
- Pediatrics, British Columbia children’s Hospital, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
| | - Kevan Jacobson
- Division of Gastroenterology, Hepatology and Nutrition, British Columbia Children’s Hospital, Vancouver, BC V6H 3V4, Canada
- Pediatrics, B.C. Children’s Hospital Research Institute, Vancouver, BC V6H 3V4, Canada
- Department of Cellular and Physiological Sciences, Faculty of Medicine, Vancouver, BC V6T 1Z3, Canada
- Pediatrics, British Columbia children’s Hospital, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
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20
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Monteiro S, Dias de Castro F, Leite S, Moreira MJ, Cotter J. Low fecal calprotectin predicts clinical remission in Crohn's disease patients: the simple answer to a challenging question. Scand J Gastroenterol 2019; 54:49-54. [PMID: 30663515 DOI: 10.1080/00365521.2018.1549683] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 11/03/2018] [Accepted: 11/11/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIM Fecal calprotectin (FC) is a noninvasive marker of intestinal inflammation. Predicting relapses in Crohn's disease (CD) patients can allow earlier changes in therapy. The aim of this study was to evaluate the role of FC in predicting relapse in CD patients in clinical remission within six months follow-up. METHODS Patients with CD who were in clinical remission at least ≥3 months were included in this study. The first FC sample during the remission period was evaluated and was used as the baseline value. Relapse was defined as an unexpected escalation in therapy, hospitalization or need for surgery for active CD. The accuracy and optimal cutoff FC values for predicting clinical relapse at six months were assessed by the area under the ROC curve (AUC). RESULTS One hundred and forty-four patients were evaluated, with mean age of 38.4 years. Of these, 13 (9%) had a relapse during the follow-up period. The mean FC value was significantly lower for non-relapsers (203.2 μg/g) than for relapsers (871.3 μg/g), p < .001. The AUC for predicting relapse by using FC values was 0.924. The optimal cutoff FC value to predict relapse was 327 μg/g; with values of sensitivity, specificity, negative predictive value and positive predictive value were 92.3%, 82.4%, 99.1% and 34.3%, respectively. CONCLUSIONS FC is more useful in predicting remission maintenance than relapse in patients with CD in clinical remission. Values of FC ≤327 μg/g can exclude relapse at least at six months follow-up period.
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Affiliation(s)
- Sara Monteiro
- a Gastroenterology Department , Hospital da Senhora da Oliveira , Guimarães , Portugal
- b School of Medicine , Life and Health Sciences Research Institute (ICVS), University of Minho , Braga/Guimarães , Portugal
- c ICVS/3B's, PT Government Associate Laboratory , Braga/Guimarães , Portugal
| | - Francisca Dias de Castro
- a Gastroenterology Department , Hospital da Senhora da Oliveira , Guimarães , Portugal
- b School of Medicine , Life and Health Sciences Research Institute (ICVS), University of Minho , Braga/Guimarães , Portugal
- c ICVS/3B's, PT Government Associate Laboratory , Braga/Guimarães , Portugal
| | - Sílvia Leite
- a Gastroenterology Department , Hospital da Senhora da Oliveira , Guimarães , Portugal
- b School of Medicine , Life and Health Sciences Research Institute (ICVS), University of Minho , Braga/Guimarães , Portugal
- c ICVS/3B's, PT Government Associate Laboratory , Braga/Guimarães , Portugal
| | - Maria João Moreira
- a Gastroenterology Department , Hospital da Senhora da Oliveira , Guimarães , Portugal
- b School of Medicine , Life and Health Sciences Research Institute (ICVS), University of Minho , Braga/Guimarães , Portugal
- c ICVS/3B's, PT Government Associate Laboratory , Braga/Guimarães , Portugal
| | - José Cotter
- a Gastroenterology Department , Hospital da Senhora da Oliveira , Guimarães , Portugal
- b School of Medicine , Life and Health Sciences Research Institute (ICVS), University of Minho , Braga/Guimarães , Portugal
- c ICVS/3B's, PT Government Associate Laboratory , Braga/Guimarães , Portugal
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21
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Iwamoto F, Matsuoka K, Motobayashi M, Takenaka K, Kuno T, Tanaka K, Tsukui Y, Kobayashi S, Yoshida T, Fujii T, Saito E, Yamaguchi T, Nagahori M, Sato T, Ohtsuka K, Enomoto N, Watanabe M. Prediction of disease activity of Crohn's disease through fecal calprotectin evaluated by balloon-assisted endoscopy. J Gastroenterol Hepatol 2018; 33:1984-1989. [PMID: 29889986 DOI: 10.1111/jgh.14310] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 05/15/2018] [Accepted: 05/24/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIM Fecal calprotectin (FC) is a useful marker for assessing the activity of intestinal inflammation. However, most studies have used ileocolonoscopy to evaluate the association of FC with intestinal inflammation, and it is not clear whether FC is useful for the evaluation of small-bowel Crohn's disease (CD). This study aimed to determine the usefulness of FC for predicting intestinal inflammation evaluated by balloon-assisted endoscopy (BAE), which can visualize the deep small intestine. METHODS This was a cross-sectional, observational study involving 69 CD patients, 39 of whom had only small-bowel disease. The extended simplified endoscopic activity score for Crohn's disease (eSES-CD) was calculated based on the findings of BAE. Mucosal healing was defined as an eSES-CD of 0. RESULTS In all CD patients, FC levels were correlated with the eSES-CD (r = 0.663, P < 0.001). The cutoff value to predict mucosal healing was 92 mg/kg, with a sensitivity of 94%, specificity of 88%, positive predictive value of 98%, negative predictive value of 64%, and the area under the curve of 0.91. Even in small-bowel CD patients, FC levels were correlated with the eSES-CD (r = 0.607, P < 0.001). The cutoff value was 92 mg/kg, with a sensitivity of 87%, specificity of 88%, positive predictive value of 96%, negative predictive value of 64%, and area under the curve of 0.85. CONCLUSIONS Fecal calprotectin showed a significant correlation with the intestinal inflammation evaluated with BAE even in patients with only small intestinal disease. FC is useful for the evaluation of CD including both the small and large intestines.
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Affiliation(s)
- Fumihiko Iwamoto
- Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.,First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Katsuyoshi Matsuoka
- Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Maiko Motobayashi
- Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kento Takenaka
- Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Toru Kuno
- First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Keisuke Tanaka
- First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Yuya Tsukui
- First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Shoji Kobayashi
- First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Takashi Yoshida
- First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Toshimitsu Fujii
- Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Eiko Saito
- Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Tatsuya Yamaguchi
- First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Masakazu Nagahori
- Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Tadashi Sato
- First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Kazuo Ohtsuka
- Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
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22
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Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the utility of the determination of faecal calprotectin in inflammatory bowel disease. ACTA ACUST UNITED AC 2018. [DOI: 10.1016/j.gastre.2018.05.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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23
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Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre la utilidad de la determinación de calprotectina fecal en la enfermedad inflamatoria intestinal. GASTROENTEROLOGIA Y HEPATOLOGIA 2018; 41:514-529. [DOI: 10.1016/j.gastrohep.2018.05.029] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 05/03/2018] [Accepted: 05/03/2018] [Indexed: 12/14/2022]
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24
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Tham YS, Yung DE, Fay S, Yamamoto T, Ben-Horin S, Eliakim R, Koulaouzidis A, Kopylov U. Fecal calprotectin for detection of postoperative endoscopic recurrence in Crohn's disease: systematic review and meta-analysis. Therap Adv Gastroenterol 2018; 11:1756284818785571. [PMID: 30034529 PMCID: PMC6048608 DOI: 10.1177/1756284818785571] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 06/06/2018] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Anastomotic recurrence is frequent in patients with Crohn's disease (CD) following ileocecal resection. The degree of endoscopic recurrence, quantified by the Rutgeerts score (RS), correlates with risk of clinical and surgical recurrence. Several studies demonstrate the accuracy of fecal calprotectin (FC) for detection of endoscopic recurrence, however the optimal threshold FC value remains to be established. The aim of our meta-analysis was to evaluate the accuracy of common FC cut-offs for detection of endoscopic recurrence. METHODS We performed a systematic literature search for studies evaluating postoperative recurrence in CD which reported RS and FC levels. Endoscopic recurrence was defined as RS = 2-4 (or RS ⩾ 2). We calculated pooled diagnostic sensitivity, specificity, diagnostic odds ratio (DOR) and constructed summary receiver operating characteristic (SROC) curves for each available FC cut-off value. RESULTS A total of 54 studies were retrieved; 9 studies were eligible for analysis. Diagnostic accuracy was calculated for FC values of 50, 100, 150 and 200 µg/g. A significant threshold effect was observed for all FC values. The optimal diagnostic accuracy was obtained for FC value of 150 µg/g, with a pooled sensitivity of 70% [95% confidence interval (CI) 59-81%], specificity 69% (95% CI 61-77%), and DOR 5.92 (95% CI 2.61-12.17). The area under the SROC curve was 0.73. CONCLUSION FC is an accurate surrogate marker of postoperative endoscopic recurrence in CD patients. The FC cut-off 150 μg/g appears to have the best overall accuracy. Serial FC evaluations may eliminate or defer the need for colonoscopic evaluation in up to 70% of postoperative CD patients.
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Affiliation(s)
- Yuen Sau Tham
- Centre for Liver & Digestive Disorders, The
Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Diana E. Yung
- Centre for Liver & Digestive Disorders, The
Royal Infirmary of Edinburgh, Edinburgh, UK
| | - Shmuel Fay
- Department of Gastroenterology, Sheba Medical
Centre, Ramat Gan, Israel Sackler School of Medicine, Tel-Aviv University,
Tel-Aviv, Israel
| | - Takayuki Yamamoto
- Inflammatory Bowel Disease Centre, Yokkaichi
Social Insurance Hospital, Yokkaichi, Mie, Japan
| | - Shomron Ben-Horin
- Department of Gastroenterology, Sheba Medical
Centre, Ramat Gan, Israel Sackler School of Medicine, Tel-Aviv University,
Tel-Aviv, Israel
| | - Rami Eliakim
- Department of Gastroenterology, Sheba Medical
Centre, Ramat Gan, Israel Sackler School of Medicine, Tel-Aviv University,
Tel-Aviv, Israel
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25
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Abdelmaksoud A. Peristomal psoriasis: an extraintestinal manifestation of inflammatory bowel disease? Int J Dermatol 2018; 57:747-748. [DOI: 10.1111/ijd.13987] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Revised: 03/02/2018] [Accepted: 03/05/2018] [Indexed: 11/29/2022]
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26
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Galgut BJ, Lemberg DA, Day AS, Leach ST. The Value of Fecal Markers in Predicting Relapse in Inflammatory Bowel Diseases. Front Pediatr 2018; 5:292. [PMID: 29404311 PMCID: PMC5780398 DOI: 10.3389/fped.2017.00292] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Accepted: 12/20/2017] [Indexed: 12/12/2022] Open
Abstract
The inflammatory bowel diseases (IBDs) are lifelong chronic illnesses that place an immense burden on patients. The primary aim of therapy is to reduce disease burden and prevent relapse. However, the occurrence of relapses is often unpredictable. Current disease monitoring is primarily by way of clinical indices, with relapses often only recognized once the inflammatory episode is established with subsequent symptoms and gut damage. The window between initial upregulation of the inflammatory response and the recognition of symptoms may provide an opportunity to prevent the relapse and associated morbidity. This review will describe the existing literature surrounding predictive indicators of relapse of IBD with a specific focus on fecal biomarkers. Fecal biomarkers offer promise as a convenient, non-invasive, low cost option for disease monitoring that is predictive of subsequent relapse. To exploit the potential of fecal biomarkers in this role, further research is now required. This research needs to assess multiple fecal markers in context with demographics, disease phenotype, genetics, and intestinal microbiome composition, to build disease behavior models that can provide the clinician with sufficient confidence to intervene and change the long-term disease course.
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Affiliation(s)
- Bianca J. Galgut
- School of Women’s and Children’s Health, University of New South Wales, Sydney, NSW, Australia
| | - Daniel A. Lemberg
- School of Women’s and Children’s Health, University of New South Wales, Sydney, NSW, Australia
- Department of Gastroenterology, Sydney Children’s Hospital Randwick, Sydney, NSW, Australia
| | - Andrew S. Day
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Steven T. Leach
- School of Women’s and Children’s Health, University of New South Wales, Sydney, NSW, Australia
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27
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Chew TS, Mansfield JC. Can faecal calprotectin predict relapse in inflammatory bowel disease: a mini review. Frontline Gastroenterol 2018; 9:23-28. [PMID: 29484157 PMCID: PMC5824761 DOI: 10.1136/flgastro-2016-100686] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Revised: 03/04/2016] [Accepted: 03/11/2016] [Indexed: 02/07/2023] Open
Abstract
Crohn's disease and ulcerative colitis are chronic inflammatory disorders affecting the gastrointestinal tract. Faecal calprotectin is a protein complex of the S-100 family of calcium-binding proteins present in inflammatory cells that can be measured in stool samples, which act as a biomarker for bowel inflammation. Elevated faecal calprotectin has been shown to reflect the presence of ongoing mucosal inflammation, which improves with mucosal healing. The aim of this review was to evaluate the available evidence on the ability of faecal calprotectin to predict a relapse in inflammatory bowel disease. Multiple retrospective studies have shown that patients who relapse have significantly higher levels of calprotectin in their stool compared with non-relapsers, especially in ulcerative colitis. Elevated faecal calprotectin postoperatively in Crohn's disease was also shown to be indicative of a relapse. However, the association of a raised faecal calprotectin and relapse is not universal and may be explained by the different patterns of mucosal inflammatory activity that exist. In conclusion, we put forward our hypothesis that changes such as a rise in faecal calprotectin levels may be more predictive of a relapse than absolute values.
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Affiliation(s)
- T S Chew
- Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Newcastle upon Tyne, UK
| | - J C Mansfield
- Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Newcastle upon Tyne, UK
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28
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Abstract
Calprotectin is a 36kDa member of the S100 family of proteins. It is derived predominantly from neutrophils and has direct antimicrobial effects and a role within the innate immune response. Calprotectin is found in various body fluids in proportion to the degree of any existing inflammation and its concentration in feces is about six times that of plasma. Measurement of fecal calprotectin is a useful surrogate marker of gastrointestinal inflammation. It has a high negative predictive value in ruling out inflammatory bowel disease (IBD) in undiagnosed, symptomatic patients and a high sensitivity for diagnosing the disease making it useful as a tool for prioritising endoscopy. In patients with known IBD, fecal calprotectin can be a useful tool to assist management, providing evidence of relapse or mucosal healing to enable therapy to be intensified or reduced. There are a number of commercial calprotectin assays with marked difference in performance as judged by external quality assessment and at present no standardised reference material exists. Various factors may affect results including age, medication and day to day variation. Laboratories should therefore be mindful of the characteristics of their own assay and factors that may affect results.
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Affiliation(s)
- Ruth M Ayling
- FRCPath Consultant Chemical Pathologist, Clinical Biochemistry, Pathology and Pharmacy Building, Royal London Hospital, London, United Kingdom
| | - Klaartje Kok
- MRCP Consultant Gastroenterologist, Barts Health NHS Trust, London, United Kingdom
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29
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Kostas A, Siakavellas SI, Kosmidis C, Takou A, Nikou J, Maropoulos G, Vlachogiannakos J, Papatheodoridis GV, Papaconstantinou I, Bamias G. Fecal calprotectin measurement is a marker of short-term clinical outcome and presence of mucosal healing in patients with inflammatory bowel disease. World J Gastroenterol 2017; 23:7387-7396. [PMID: 29151692 PMCID: PMC5685844 DOI: 10.3748/wjg.v23.i41.7387] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Revised: 09/18/2017] [Accepted: 09/29/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the utility of fecal calprotectin (FC) in predicting relapse and endoscopic activity during follow-up in an inflammatory bowel disease (IBD) cohort. METHODS All FC measurements that were obtained during a 3-year period from patients with inflammatory bowel disease in clinical remission were identified. Data regarding the short-term (6 mo) course of the disease were extracted from the medical files. Exclusion criteria were defined as: (1) An established flare of the disease at the time of FC measurement, (2) Loss to follow up within 6 mo from baseline FC measurement, and, (3) Insufficient data on file. Statistical analysis was performed to evaluate whether baseline FC measurement could predict the short term clinical relapse and/or the presence of mucosal healing. RESULTS We included 149 [Crohn's disease (CD) = 113, Ulcerative colitis (UC) = 36, male = 77] IBD patients in our study. Within the determined 6-month period post-FC measurement, 47 (31.5%) had a disease flare. Among 76 patients who underwent endoscopy, 39 (51.3%) had mucosal healing. Baseline FC concentrations were significantly higher in those who had clinical relapse compared to those who remained in remission during follow up (481.0 μg/g, 286.0-600.0 vs 89.0, 36.0-180.8, P < 0.001). The significant predictive value of baseline median with IQR FC for clinical relapse was confirmed by multivariate Cox analysis [HR for 100μg/g: 1.75 (95%CI: 1.28-2.39), P = 0.001]. Furthermore, lower FC baseline values significantly correlated to the presence of mucosal healing in endoscopy (69.0 μg/g, 30.0-128.0 vs 481.0, 278.0-600.0, in those with mucosal inflammation, median with IQR, P < 0.001). We were able to extract cut-off values for FC concentration with a high sensitivity and specificity for predicting clinical relapse (261 μg/g with AUC = 0.901, sensitivity 87.2%, specificity 85.3%, P < 0.001) or mucosal healing (174 μg/g with AUC = 0.956, sensitivity 91.9%, specificity 87.2%, P < 0.001). FC was better than CRP in predicting either outcome; nevertheless, having a pathological CRP (> 5 mg/L) in addition to the cut-offs for FC, significantly enhanced the specificity for predicting clinical relapse (95.1% from 85.3%) or endoscopic activity (100% from 87.2%). CONCLUSION Serial FC measurements may be useful in monitoring IBD patients in remission, as FC appears to be a reliable predictor of short-term relapse and endoscopic activity.
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Affiliation(s)
- Athanasios Kostas
- Academic Department of Gastroenterology, University of Athens Medical School, Laiko General Hospital, Athens 11527, Greece
| | - Spyros I Siakavellas
- Academic Department of Gastroenterology, University of Athens Medical School, Laiko General Hospital, Athens 11527, Greece
| | - Charalambos Kosmidis
- Academic Department of Gastroenterology, University of Athens Medical School, Laiko General Hospital, Athens 11527, Greece
| | - Anna Takou
- Biochemistry Department, Laiko General Hospital, Athens 11527, Greece
| | - Joanna Nikou
- Biochemistry Department, Laiko General Hospital, Athens 11527, Greece
| | | | - John Vlachogiannakos
- Academic Department of Gastroenterology, University of Athens Medical School, Laiko General Hospital, Athens 11527, Greece
| | - George V Papatheodoridis
- Academic Department of Gastroenterology, University of Athens Medical School, Laiko General Hospital, Athens 11527, Greece
| | - Ioannis Papaconstantinou
- 2nd Department of Surgery, University of Athens Medical School, Areteion General Hospital, Athens 11528, Greece
| | - Giorgos Bamias
- Academic Department of Gastroenterology, University of Athens Medical School, Laiko General Hospital, Athens 11527, Greece
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30
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Ye L, Chen BQ, Wang SD, Shi H, Yang Z, Wang FY. Fecal calprotectin is a strong predictive marker of relapse in Chinese patients with Crohn's disease: a two-year prospective study. Scand J Gastroenterol 2017; 52:1113-1119. [PMID: 28675068 DOI: 10.1080/00365521.2017.1346704] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To evaluate the predictive value of fecal calprotectin (FC) for clinical relapse in Chinese patients with quiescent Crohn's disease (CD) and to further investigate the correlation between FC and intestinal inflammation. METHODS Sixty-two patients with a diagnosis of quiescent CD were consecutively enrolled in this prospective study. Fecal samples were collected and enteroscopy were performed to detect mucosal lesions at the beginning of the study. Patients were followed until the first relapse or by the end of the two-year follow-up. The calprotectin concentration was measured using a quantitative enzyme-linked immunoassay. RESULTS Of the 62 CD patients, 29 had a relapse (median time of relapse: 8.44 months). The median follow-up months was 8.16 (4.98-13.59). The cut off level of 225 μg/g provided the maximal area under the receiver operating characteristic curve (AUC) of .775 for detecting the relapse of CD patients. Meanwhile, fecal occult blood had an added value. The multivariate Cox regression model showed that FC was the strongest predictor of the risk of relapse (risk ratio (RR): 6.315; p = .001). FC correlated most closely with the simple endoscopic score for Crohn's disease (SES-CD) (r = 0.524, p < .001). CONCLUSIONS FC correlated significantly with gut inflammation and could be a reliable predictor of relapse in Chinese patients with CD.
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Affiliation(s)
- Lei Ye
- a Department of Gastroenterology and Hepatology , Jinling Hospital, Medical School of Nanjing University , Nanjing , Jiangsu Province , China
| | - Bi Qin Chen
- b Department of Gastroenterology and Hepatology , Jinling Hospital, Clinical Medical School of Southern Medical University , Nanjing , China
| | - Shao Dong Wang
- a Department of Gastroenterology and Hepatology , Jinling Hospital, Medical School of Nanjing University , Nanjing , Jiangsu Province , China
| | - Hui Shi
- a Department of Gastroenterology and Hepatology , Jinling Hospital, Medical School of Nanjing University , Nanjing , Jiangsu Province , China
| | - Zhao Yang
- b Department of Gastroenterology and Hepatology , Jinling Hospital, Clinical Medical School of Southern Medical University , Nanjing , China
| | - Fang Yu Wang
- a Department of Gastroenterology and Hepatology , Jinling Hospital, Medical School of Nanjing University , Nanjing , Jiangsu Province , China
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31
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Kwapisz L, Gregor J, Chande N, Yan B, Ponich T, Mosli M. The utility of fecal calprotectin in predicting the need for escalation of therapy in inflammatory bowel disease. Scand J Gastroenterol 2017; 52:846-850. [PMID: 28423962 DOI: 10.1080/00365521.2017.1315740] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Fecal calprotectin is an important biomarker used in the evaluation of inflammatory bowel disease. It has proven to be an effective tool in initial screening as well monitoring response to therapy. The aim of this study is to examine the utility of fecal calprotectin both as a predictor for the escalation of therapy in established inflammatory bowel disease and as a predictor of de novo diagnosis. METHODS Patients with signs and symptoms concerning for inflammatory bowel disease presenting to outpatient clinics were recruited to provide fecal calprotectin stool samples prior to endoscopic evaluation. Patients were followed up for at least one year and monitored clinically for any change in symptomatology, escalation of therapy or development of IBD, confirmed endoscopically. RESULTS A total of 126 patients, of whom 72 were known to have underlying inflammatory bowel disease, were included in the final analysis. Among the patients with elevated fecal calprotectin levels and known inflammatory bowel disease, 66% (33/50) went on to have escalation of therapy within 12 months compared to 18% (4/22) if the fecal calprotectin levels were in the normal range (p < .0001). For the remaining patients who at baseline did not have inflammatory bowel disease and a normal endoscopic evaluation, elevated fecal calprotectin resulted in no cases (0/17) of a new diagnosis in the next 12 months. CONCLUSIONS Fecal calprotectin is a useful test for predicting escalation of therapy in established inflammatory bowel disease.
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Affiliation(s)
- Lukasz Kwapisz
- a Department of Medicine, Division of Gastroenterology , London Health Sciences Centre (LHSC), Western University , London , Ontario , Canada
| | - Jamie Gregor
- a Department of Medicine, Division of Gastroenterology , London Health Sciences Centre (LHSC), Western University , London , Ontario , Canada
| | - Nilesh Chande
- a Department of Medicine, Division of Gastroenterology , London Health Sciences Centre (LHSC), Western University , London , Ontario , Canada
| | - Brian Yan
- a Department of Medicine, Division of Gastroenterology , London Health Sciences Centre (LHSC), Western University , London , Ontario , Canada
| | - Terry Ponich
- a Department of Medicine, Division of Gastroenterology , London Health Sciences Centre (LHSC), Western University , London , Ontario , Canada
| | - Mahmoud Mosli
- b Department of Medicine, Division of Gastroenterology , King Abdulaziz University , Jeddah , Saudi Arabia
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32
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Harris V, Smith SD. Chronic cheilitis: Faecal calprotectin test a way to diagnose oral Crohn's disease. Australas J Dermatol 2017; 58:324-325. [DOI: 10.1111/ajd.12598] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Victoria Harris
- Department of Dermatology; Royal North Shore Hospital; Sydney Australia
| | - Saxon D Smith
- Northern Clinical School; University of Sydney; St Leonards Australia
- Department of Dermatology; Royal North Shore Hospital; St Leonards Australia
- The Dermatology and Skin Cancer Centre; Gosford New South Wales Australia
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33
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Diederen K, Hoekman DR, Leek A, Wolters VM, Hummel TZ, de Meij TG, Koot BGP, Tabbers MM, Benninga MA, Kindermann A. Raised faecal calprotectin is associated with subsequent symptomatic relapse, in children and adolescents with inflammatory bowel disease in clinical remission. Aliment Pharmacol Ther 2017; 45:951-960. [PMID: 28138990 DOI: 10.1111/apt.13950] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 10/27/2016] [Accepted: 12/29/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND Reliable data on inflammatory biomarkers for predicting relapse of paediatric inflammatory bowel disease (IBD) are lacking. AIM To investigate the predictive value of faecal calprotectin (FC) and CRP for symptomatic relapse in pediatric IBD in clinical remission. METHODS In this cross-sectional cohort study, patients <18 years with Crohn's disease or ulcerative colitis in clinical remission ≥3 months were included. At baseline, clinical and biochemical disease activity were assessed using the abbreviated-Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative Colitis Activity Index, and FC and CRP respectively. Disease course over the subsequent 12 months was retrospectively assessed. RESULTS In total, 114 patients (56% males; median age 14.9 years) were included. Baseline FC was higher in patients that developed symptomatic relapse [median (IQR), relapse 370 μg/g (86-1100) vs. remission 122 μg/g (40-344), P = 0.003]. Baseline FC was predictive of symptomatic relapse within 6 months [HR per 250 μg/g (95% CI): 1.46 (1.21-1.77), P < 0.001], with good predictive accuracy (AUC: 0.82). Optimal FC cut-off was 350 μg/g, with positive and negative predictive value of 41% and 96%. Baseline CRP was higher in patients that developed symptomatic relapse [median (IQR), relapse 1.0 μg/g (0.6-5.0) vs. remission 1.0 μg/g (0.4-2.0), P = 0.033]. Baseline CRP was predictive of symptomatic relapse within 6 months from baseline [HR per 1 mg/L (95% CI): 1.10 (1.02-1.19), P = 0.011], with fair predictive accuracy (AUC: 0.72). Optimal CRP cut-off was 1.0 mg/L, with positive and negative predictive value of 21% and 94%. CONCLUSIONS Faecal calprotectin and CRP are predictive of symptomatic relapse and may be valuable in management of paediatric IBD in clinical remission.
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Affiliation(s)
- K Diederen
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands
| | - D R Hoekman
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands
| | - A Leek
- Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
| | - V M Wolters
- Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
| | - T Z Hummel
- Department of Pediatrics, Medisch Spectrum Twente, Enschede, The Netherlands
| | - T G de Meij
- Department of Pediatric Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands
| | - B G P Koot
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands
| | - M M Tabbers
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands
| | - M A Benninga
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands
| | - A Kindermann
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands
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Manceau H, Chicha-Cattoir V, Puy H, Peoc'h K. Fecal calprotectin in inflammatory bowel diseases: update and perspectives. Clin Chem Lab Med 2017; 55:474-483. [PMID: 27658156 DOI: 10.1515/cclm-2016-0522] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 07/29/2016] [Indexed: 12/14/2022]
Abstract
Inflammatory bowel diseases (IBDs) are chronic diseases that result from the inflammation of the intestinal wall, suspected in any patient presenting with intestinal symptoms. Until recently, the diagnosis was mainly based on both clinical and endoscopic arguments. The use of an easy, fast, reliable, non-invasive, and inexpensive biological assay is mandatory not only in diagnosis but also in evolutionary and therapeutic monitoring. To date, the fecal calprotectin is the most documented in this perspective. This marker allows the discrimination between functional and organic bowel processes with good performance. The determination of the fecal calprotectin level contributes to the evaluation of the degree of disease activity and to monitoring of therapeutic response.
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Level of Fecal Calprotectin Correlates With Severity of Small Bowel Crohn's Disease, Measured by Balloon-assisted Enteroscopy and Computed Tomography Enterography. Clin Gastroenterol Hepatol 2017; 15:56-62. [PMID: 27565523 DOI: 10.1016/j.cgh.2016.08.015] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Revised: 08/05/2016] [Accepted: 08/11/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Previous studies have not found a correlation between fecal level of calprotectin and small bowel Crohn's disease (CD). However, these studies evaluated patients mainly by ileocolonoscopy, which views up to only the terminal ileum rather than entire small intestine. We investigated whether level of fecal calprotectin (FC) is a marker of active CD of the small bowel, identified by balloon-assisted enteroscopy and computed tomography enterography (CTE). METHODS We performed a prospective study of 123 patients with CD (35 with ileitis, 72 with ileocolitis, and 16 with colitis) evaluated by balloon-assisted enteroscopy from May 2012 through July 2015 at Toho University Sakura Medical Centre in Japan. Patients with strictures detected by balloon-assisted enteroscopy were evaluated by CTE (n = 17). Fecal samples were collected from each patient, and levels of calprotectin were measured; patient demographic variables and medical history were also collected. We developed a CTE scoring system for disease severity that was based on bowel wall thickness, mural hyperenhancement, and engorged vasa recta. The association between level of FC and simple endoscopic index for CD score or CTE was evaluated by using Spearman rank correlation coefficient. RESULTS Level of FC correlated with the simple endoscopic index for CD score (r = 0.6362, P < .0001), even in patients with only active disease of the small intestine (r = 0.6594, P = .0005). In the 17 patients with strictures that could not be passed with the enteroscope, CTE detected all lesions beyond the strictures as well as areas in the distal side of the strictures. Level of FC correlated with CTE score in these patients (r = 0.4018, P = .0011, n = 63). In receiver operating characteristic analyses, the FC cutoff value for mucosal healing was 215 μg/g; this cutoff value identified patients with healing with 82.8% sensitivity, 71.4% specificity, positive predictive value of 74.3%, negative predictive value of 80.6%, odds ratio of 12.0, and area under the receiver operating characteristic curve value of 0.81. CONCLUSIONS A combination of measurement of level of FC and CTE appears to be effective for monitoring CD activity in patients with small intestinal CD, including patients with strictures that cannot be passed by conventional endoscopy.
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Abstract
Despite advances in our understanding of the pathophysiology underlying inflammatory bowel disease, there remains a significant need for biomarkers that can differentiate between Crohn's disease and ulcerative colitis with high sensitivity and specificity, in a cost-efficient manner. As the focus on personalized approaches to the delivery of medical treatment increases, new biomarkers are being developed to predict an individual's response to therapy and their overall disease course. In this review, we will outline many of the existing and recently developed biomarkers, detailing their role in the assessment of patients with inflammatory bowel disease. We will identify opportunities for improvement in our biomarkers, including better differentiation between the subtypes of inflammatory bowel disease. We will also discuss new targets and strategies in biomarker development, including combining modalities to create biomarker signatures to improve the ability to predict disease courses and response to therapy among individual patients.
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Diagnostic Value of Fecal Calprotectin (S100 A8/A9) Test in Children with Chronic Abdominal Pain. Gastroenterol Res Pract 2016; 2016:8089217. [PMID: 27974886 PMCID: PMC5126428 DOI: 10.1155/2016/8089217] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Revised: 09/28/2016] [Accepted: 10/19/2016] [Indexed: 12/22/2022] Open
Abstract
Objectives. The aim of the study was to establish whether fecal calprotectin concentration (FCC) may be useful in children with chronic abdominal pain to differentiate between inflammatory bowel disease (IBD), other inflammatory gastrointestinal disorders, and functional gastrointestinal disorders. Methods. The study included 163 patients (median age 13 years), who were assigned to four study groups: group 0 (control), 22 healthy children; group 1, 33 children with functional gastrointestinal disorders; group 2, 71 children with inflammatory gastrointestinal disorders other than IBD; group 3, 37 children with IBD. FCC was measured using ELISA assay. Results. In group 0 and group 1 FCCs were below 100 μg/g. Low FCCs were found in 91% of patients in group 2. In patients with IBD FCCs were markedly elevated with median value of 1191.5 μg/g. However, in children with inflammatory gastrointestinal disorders other than IBD and in children with IBD mean FCCs were significantly higher compared with the control group. Significant differences in FCCs were also found between group 1 and group 2, between group 1 and group 3, and between group 2 and group 3. Conclusion. FCC is the best parameter allowing for differentiation between IBD, other inflammatory gastrointestinal disorders, and functional gastrointestinal disorders. High FCC is associated with a high probability of IBD and/or other inflammatory gastrointestinal disorders, and it allows excluding functional gastrointestinal disorders.
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Fecal calprotectin for the prediction of small-bowel Crohn's disease by capsule endoscopy: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2016; 28:1137-44. [PMID: 27415156 DOI: 10.1097/meg.0000000000000692] [Citation(s) in RCA: 80] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Fecal calprotectin is a well-established marker of mucosal inflammation. Although the correlation of elevated calprotectin levels with colonic inflammation has been confirmed repeatedly, it is less established for the small bowel. The aim of the current study was to assess the diagnostic accuracy of calprotectin for the prediction of active small-bowel disease on capsule endoscopy by performing a diagnostic test meta-analysis. MATERIALS AND METHODS A comprehensive search was performed using PubMed/Embase. Studies addressing patients with suspected/established Crohn's disease (CD) evaluated with calprotectin and videocapsule were included. A diagnostic meta-analysis was carried out; pooled diagnostic sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for each cut-off. RESULTS Seven studies (463 patients) were entered into the final analysis. The DOR was significant for all the evaluated FC cut-offs (50 μg/g: sensitivity 0.83, specificity 0.53, DOR-5.64; 100 μg/g: sensitivity 0.68, specificity 0.71, DOR-5.01; 200 μg/g: sensitivity 0.42, specificity 0.94, DOR-13.64). On sensitivity analyses, when only studies addressing suspected Crohn's or retrospective studies were included, the results did not change significantly. For studies including patients with suspected CD only, the overall accuracy for FC cut-off 50 μg/g was further increased (sensitivity 0.89, specificity 0.55, DOR-10.3), with a negative predictive value of 91.8%. SUMMARY AND CONCLUSION Fecal calprotectin has a significant diagnostic accuracy for the detection of small-bowel CD. Our results suggest that in patients with suspected CD with calprotectin <50 μg/g, the likelihood of positive diagnosis is very low.
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Jang HW, Kim HS, Park SJ, Hong SP, Kim TI, Kim WH, Cheon JH. Accuracy of three different fecal calprotectin tests in the diagnosis of inflammatory bowel disease. Intest Res 2016; 14:305-313. [PMID: 27799881 PMCID: PMC5083259 DOI: 10.5217/ir.2016.14.4.305] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 03/15/2016] [Accepted: 03/28/2016] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND/AIMS Several studies have found that the measurement of fecal calprotectin is useful for the early diagnosis of inflammatory bowel disease (IBD). We compared the effectiveness of three different fecal calprotectin kits for initial diagnosis in patients with suspected IBD. METHODS We enrolled 31 patients with IBD (18 Crohn's disease [CD], 11 ulcerative colitis [UC], and two intestinal Behçet's disease), five with irritable bowel syndrome (IBS), and five with other colitis (four infectious colitis and one intestinal tuberculosis). Diagnosis was based on clinical, laboratory, and endoscopic examinations. Fecal samples were obtained at the first diagnosis and calprotectin levels were measured using three different kits (Quantum Blue® Calprotectin, EliA™ Calprotectin, and RIDASCREEN® Calprotectin). RESULTS The overall accuracy for differentiating IBD from IBS or other colitis was 94% and 91%, respectively, for Quantum Blue® (cutoff, 50 µg/g); 92% and 89%, respectively, for EliA™ (cutoff, 50 µg/g); and 82% and 76%, respectively, for RIDASCREEN® (cutoff, 50 µg/g). In patients with CD, the results of Quantum Blue® Calprotectin and EliA™ Calprotectin correlated significantly with levels of the Crohn's disease activity index (Spearman's rank correlation coefficient, r=0.66 and r=0.49, respectively). In patients with UC, the results of EliA™ Calprotectin correlated significantly with the Mayo score (r=0.70). CONCLUSIONS Fecal calprotectin measurement is useful for the identification of IBD. The overall accuracies of the three fecal calprotectin kits are comparable.
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Affiliation(s)
- Hui Won Jang
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Sook Kim
- Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Soo Jung Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Pil Hong
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Tae Il Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Won Ho Kim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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Abstract
Mild Crohn's disease (CD) is classified as those patients who are ambulatory, with <10 % weight loss, are eating and drinking without abdominal mass, tenderness, obstructive symptoms, or fever, and endoscopically they have non-progressive mild findings. Initial evaluation of mild CD should focus on assessment for high-risk features requiring more aggressive therapy. In contrast to moderate-to-severe disease, where therapy is focused on mucosal healing, the management of mild CD is focused on symptom management, while exposing the individual to minimal therapeutic risks. Budesonide is the most commonly used medication for mild CD given its safety profile. Assessment of inflammatory markers, in concert with computed-tomography (CT) or magnetic resonance (MR) enterographies and endoscopic studies, should be considered in clinical remission to ensure that mucosal inflammation is not present. Endoscopic inflammation can precede clinical recurrence. Individuals with mild CD require routine vaccination, monitoring for iron-deficiency anemia and vitamin D deficiency, and colorectal cancer screening when appropriate.
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Affiliation(s)
- Frank I Scott
- Crohn's and Colitis Center, Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, 12605 E 16th Ave., Aurora, CO, 80045, USA.
| | - Gary R Lichtenstein
- Perelman Center for Advanced Medicine, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, 7-South, Room 753, Philadelphia, PA, 19104, USA
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Cappello M, Morreale GC. The Role of Laboratory Tests in Crohn's Disease. CLINICAL MEDICINE INSIGHTS. GASTROENTEROLOGY 2016; 9:51-62. [PMID: 27656094 PMCID: PMC4991576 DOI: 10.4137/cgast.s38203] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Revised: 07/12/2016] [Accepted: 07/16/2016] [Indexed: 02/07/2023]
Abstract
In the past, laboratory tests were considered of limited value in Crohn's disease (CD). In the era of biologics, laboratory tests have become essential to evaluate the inflammatory burden of the disease (C-reactive protein, fecal calprotectin) since symptoms-based scores are subjective, to predict the response to pharmacological options and the risk of relapse, to discriminate CD from ulcerative colitis, to select candidates to anti-tumor necrosis factors [screening tests looking for hepatitis B virus and hepatitis C virus status and latent tuberculosis], to assess the risk of adverse events (testing for thiopurine metabolites and thiopurine-methyltransferase activity), and to personalize and optimize therapy (therapeutic drug monitoring). Pharmacogenetics, though presently confined to the assessment of thiopurineme methyltransferase polymorphisms and hematological toxicity associated with thiopurine treatment, is a promising field that will contribute to a better understanding of the molecular mechanisms of the variability in response to the drugs used in CD with the attempt to expand personalized care and precision medicine strategies.
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Affiliation(s)
- Maria Cappello
- Senior Registrar in Gastroenterology, Gastroenterology and Hepatology Section, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo School of Medicine, Palermo, Italy
| | - Gaetano Cristian Morreale
- Trainee in Gastroenterology, Gastroenterology and Hepatology Section, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo School of Medicine, Palermo, Italy
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Zhuge Y, Huang QP, Li Q, Wang JS. Fecal Calprotectin for predicting Relapse and Activity in Patients with Crohn's Disease: A Meta-analysis. Euroasian J Hepatogastroenterol 2016; 6:116-124. [PMID: 29201742 PMCID: PMC5578578 DOI: 10.5005/jp-journals-10018-1182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Accepted: 06/29/2016] [Indexed: 11/23/2022] Open
Abstract
AIMS We aimed to perform a meta-analysis of the predictive capacity of fecal calprotectin (FC) in activity and relapse of Crohn's disease (CD). MATERIALS AND METHODS MEDLINE, EMBASE, and the Cochrane Library databases were searched systematically. Pooled sensitivity, specificity, and other diagnostic indices were evaluated. RESULTS A total of 1,252 CD patients from 18 different studies were analyzed. The pooled sensitivity and specificity of FC at a cutoff value of 50 μg/g to predict activity of CD were 0.91 [95% confidence interval (CI): 0.87-0.95] and 0.47 (95% CI: 0.35-0.59) respectively. The pooled sensitivity and specificity of FC at a cutoff value of larger than 150 μg/g to monitor relapse of CD was 0.75 (95% CI: 0.67-0.82) and 0.71 (95% CI: 0.66-0.76) respectively. The area under the summary receiver operating characteristic (SROC) curve of FC for detecting CD activity was 0.78 (50 μg/g), 0.88 (100 μg/g), 0.85 (>150 μg/g), and the diagnostic odds ratio (DOR) was 10.21 (50 μg/g), 10.20 (100 μg/g), 11.68 (>150 μg/g) respectively. CONCLUSION As a simple and noninvasive marker, FC is useful to predict the activity and relapse in CD patients, and the capacity of FC to predict CD activity was superior to its application in monitoring relapse of CD. HOW TO CITE THIS ARTICLE Zhuge Y, Huang Q-P, Li Q, Wang J-S. Fecal Calprotectin for predicting Relapse and Activity in Patients with Crohn's Disease: A Meta-analysis. Euroasian J Hepato-Gastroenterol 2016;6(2):116-124.
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Affiliation(s)
- Ying Zhuge
- Department of Cardiology, Affiliated Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Qiu-Ping Huang
- Department of Internal Medicine, Affiliated Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Qing Li
- Department of Internal Medicine, Affiliated Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Jun-Shan Wang
- Department of Gastroenterology, Shanghai Tenth's Hospital of Tongji University, Shanghai, China
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Utility of surrogate markers for the prediction of relapses in inflammatory bowel diseases. J Gastroenterol 2016; 51:531-47. [PMID: 26975751 DOI: 10.1007/s00535-016-1191-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Accepted: 02/21/2016] [Indexed: 02/04/2023]
Abstract
Patients with diagnosed inflammatory bowel disease (IBD) will commonly experience a clinical relapse in spite of a prolonged therapy-induced period of clinical remission. The current methods of assessing subclinical levels of low-grade inflammation which predispose patients to relapse are not optimal when considering both cost and patient comfort. Over the past few decades, much investigation has discovered that proteins such as calprotectin that are released from inflammatory cells are capable of indicating disease activity. Along with C-reactive protein and erythrocyte sedimentation rate, calprotectin has now become part of the current methodology for assessing IBD activity. More recently, research has identified that other fecal and serum biomarkers such as lactoferrin, S100A12, GM-CSF autoantibodies, α1-antitrypsin, eosinophil-derived proteins, and cytokine concentrations have variable degrees of utility in monitoring gastrointestinal tract inflammation. In order to provide direction toward novel methods of predicting relapse in IBD, we provide an up-to-date review of these biomarkers and their potential utility in the prediction of clinical relapse, given their observed activities during various stages of clinical remission.
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Fecal Immunochemical Test Versus Fecal Calprotectin for Prediction of Mucosal Healing in Crohn's Disease. Inflamm Bowel Dis 2016; 22:1078-85. [PMID: 26891256 DOI: 10.1097/mib.0000000000000728] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Mucosal healing (MH) has been proposed as a treatment goal of inflammatory bowel disease patients. We reported recently that not only fecal calprotectin (Fcal) but also the fecal immunochemical test (FIT) can predict MH in ulcerative colitis. However, the predictive power of the fecal markers for MH in Crohn's disease (CD), particularly with small bowel lesions, has not been reported in detail. The aim of this study was to evaluate the predictability of FIT versus Fcal for MH in CD. METHODS Consecutive CD patients underwent colonoscopy or balloon-assisted enteroscopy according to the disease location. FIT and Fcal were examined using stool samples collected the day before endoscopy. RESULTS Seventy-one CD patients were analyzed, of whom 42 (59%) underwent balloon-assisted enteroscopy because of the presence of affected lesions in the small intestine. Both the Fcal and the FIT results were significantly correlated with endoscopic activity (r = 0.67 and 0.54, respectively). However, the FIT results did not correlate with the activity in patients with small bowel lesions alone, whereas Fcal did (r = 0.42 versus 0.78). Fcal predicted MH in CD with 87% sensitivity and 71% specificity, whereas the values for FIT were 96% and 48%, respectively. The specificity for MH among patients with small bowel lesions alone was low for FIT (40%) compared with Fcal (80%). CONCLUSIONS Both FIT and Fcal were correlated with the mucosal status of CD. However, the specificity of FIT was not satisfactory, particularly for small bowel lesions.
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Wright EK, Kamm MA, De Cruz P, Hamilton AL, Ritchie KJ, Keenan JI, Leach S, Burgess L, Aitchison A, Gorelik A, Liew D, Day AS, Gearry RB. Comparison of Fecal Inflammatory Markers in Crohn's Disease. Inflamm Bowel Dis 2016; 22:1086-1094. [PMID: 26818420 DOI: 10.1097/mib.0000000000000671] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Fecal biomarkers are used increasingly to monitor Crohn's disease (CD). However, the relative accuracy of different markers in identifying inflammation has been poorly evaluated. We evaluated fecal calprotectin (FC), lactoferrin (FL), and S100A12 (FS) using endoscopic validation in a prospective study of the progression of CD after intestinal resection. METHODS Data were collected from 135 participants in a prospective, randomized, controlled trial aimed at preventing postoperative CD recurrence. Three hundred nineteen stool samples were tested for FC, FL, and FS preoperatively and 6, 12, and 18 months after resection. Colonoscopy was performed at 6 and/or 18 months. Endoscopic recurrence was assessed blindly using the Rutgeerts score. C-reactive protein (CRP) and Crohn's Disease Activity Index (CDAI) were assessed. RESULTS FC, FL, and FS concentrations were elevated preoperatively (median: 1347, 40.9, and 8.4 μg/g, respectively). At 6 months postoperatively, marker concentrations decreased (166, 3.0, 0.9 μg/g) and were higher in recurrent disease than remission (275 versus 72 μg/g, P < 0.001; 5.7 versus 1.6 μg/g, P = 0.007; 2.0 versus 0.8 μg/g, P = 0.188). FC > 135 μg/g, FL > 3.4 μg/g, and FS > 10.5 μg/g indicated endoscopic recurrence (score ≥ i2) with a sensitivity, specificity, and negative predictive value (NPV) of 0.87, 0.66, and 91%; 0.70, 0.68, and 81%; 0.91, 0.12, and 71%, respectively. FC and FL correlated significantly with the presence and severity of endoscopic recurrence, whereas FS, CRP and CDAI did not. CONCLUSIONS FC was the optimal fecal marker for monitoring disease activity in postoperative CD and was superior to CRP and CDAI. FL offered modest sensitivity for detecting recurrent disease, whereas S100A12 was sensitive but had low specificity and NPV.
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Affiliation(s)
- Emily K Wright
- *Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, Australia; †Imperial College London, London, United Kingdom; ‡Department of Surgery, University of Otago, Christchurch, New Zealand; §School of Women's and Children's Health, University of NSW, Sydney, Australia; ‖Department of Paediatrics, University of Otago, Christchurch, New Zealand; ¶Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, Australia; and **Department of Medicine, University of Otago, Christchurch, New Zealand
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Ahmed I, Greenwood R, Costello B, Ratcliffe N, Probert CS. Investigation of faecal volatile organic metabolites as novel diagnostic biomarkers in inflammatory bowel disease. Aliment Pharmacol Ther 2016; 43:596-611. [PMID: 26806034 DOI: 10.1111/apt.13522] [Citation(s) in RCA: 97] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 07/08/2015] [Accepted: 12/18/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND The aetiology of inflammatory bowel disease (IBD) remains poorly understood. Recent evidence suggests an important role of gut microbial dysbiosis in IBD, and this may be associated with changes in faecal volatile organic metabolites (VOMs). AIM To describe the changes in the faecal VOMs of patients with IBD and establish their diagnostic potential as non-invasive biomarkers. METHODS Faecal samples were obtained from 117 people with Crohn's disease (CD), 100 with ulcerative colitis (UC), and 109 healthy controls. Faecal VOMs were extracted using solid-phase micro-extraction and analysed by gas chromatography mass spectrometry. Data analysis was carried out using partial least squares-discriminate analysis (PLS-DA) to determine class membership based on distinct metabolomic profiles. RESULTS The PLS-DA model showed clear separation of active CD from inactive disease and healthy controls (P < 0.001). Heptanal, 1-octen-3-ol, 2-piperidinone and 6-methyl-2-heptanone were up-regulated in the active CD group [variable important in projection (VIP) score 2.8, 2.7, 2.6 and 2.4, respectively], while methanethiol, 3-methyl-phenol, short-chain fatty acids and ester derivatives were found to be less abundant (VIP score of 3.5, 2.6, 1.5 and 1.2, respectively). The PLS-DA model also separated patients with small bowel CD from healthy controls and those with colonic CD from UC (P < 0.001). In contrast, less distinct separation was observed between active UC, inactive UC and healthy controls. CONCLUSIONS Analysis of faecal volatile organic metabolites can provide an understanding of gut metabolomic changes in IBD. It has the potential to provide a non-invasive means of diagnosing IBD, and can differentiate between UC and CD.
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Affiliation(s)
- I Ahmed
- Department of Gastroenterology, University Hospital Southampton, Southampton, UK
| | - R Greenwood
- Department of Research and Development, Bristol Royal Infirmary, Bristol, UK
| | - B Costello
- Institute of Biosensing Technology, University of the West of England, Bristol, UK
| | - N Ratcliffe
- Institute of Biosensing Technology, University of the West of England, Bristol, UK
| | - C S Probert
- Gastroenterology Research Unit, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
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Hosseini SV, Safarpour AR, Taghavi SA. Developing a novel risk-scoring system for predicting relapse in patients with ulcerative colitis: A prospective cohort study. Pak J Med Sci 2016; 31:1511-6. [PMID: 26870126 PMCID: PMC4744311 DOI: 10.12669/pjms.316.8811] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES Ulcerative Colitis (UC) follows a natural clinical course of relapses and remissions. The aim of this study was to construct a risk-scoring formula in order to enable predicting relapses in patients with UC. METHODS From October 2012 to October 2013, 157 patients from Shiraz, southern Iran who were diagnosed with UC and in remission were enrolled. At 3-month intervals, multiple risk factors of hemoglobin, complete blood counts, serum iron and albumin, erythrocyte sedimentation rate, and faecal calprotectin levels, sex, age, cigarette smoking, positive family history of inflammatory bowel diseases, past history of appendectomy, extra-intestinal accompanying diseases, extent of disease at the beginning of study, number of previous relapses, duration of disease and duration of remission before the study were assessed. Univariate and multivariate logistic regression were applied to fit the final model. The new risk-scoring system accuracy was assessed using receiver-operating-characteristics (ROC) curve analysis. RESULTS Seventy four patients (48.1%) experienced a relapse. Multivariate analysis revealed that relapses could significantly be predicted by the level of fecal calprotectin (OR=8.1), age (OR=9.2), the Seo activity index (OR=52.7), and the number of previous relapses (OR=4.2). The risk scoring formula was developed using the regression coefficient values of the aforementioned variables. CONCLUSION Four predictor variables were significant in the final model and were used in our risk-scoring formula. It is recommended that patients who achieve high scores are diligently observed, treated, and followed up.
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Affiliation(s)
- Seyed Vahid Hosseini
- Seyed Vahid Hosseini, Colorectal Research Center, Faghihi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Reza Safarpour
- Ali Reza Safarpour, Gastroenterohepatology Research Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Alireza Taghavi
- Seyed Alireza Taghavi, Gastroenterohepatology Research Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
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Abstract
Inflammatory bowel disease (IBD) and irritable bowel syndrome share many symptoms. While irritable bowel syndrome is a functional bowel disorder for which no specific treatment is available, the range of effective therapies for IBD is evolving rapidly. Accurate diagnosis of IBD is therefore essential. Clinical assessment, together with various imaging modalities and endoscopy, has been the mainstay of diagnosis for many years. Fecal biomarkers of gastrointestinal inflammation have appeared in the past decade, of which calprotectin, a neutrophil cytosolic protein, has been studied the most. Crohn’s disease and ulcerative colitis are chronic remitting and relapsing diseases, and objective assessment of disease activity and response to treatment are important. This review focuses on the use of fecal calprotectin measurements in the diagnosis and monitoring of patients with IBD.
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Affiliation(s)
- Natalie E Walsham
- Department of Clinical Biochemistry, University Hospital Lewisham, Lewisham, London, UK
| | - Roy A Sherwood
- Department of Clinical Biochemistry, Viapath at King's College Hospital NHS Foundation Trust, London, UK
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Liverani E, Scaioli E, Digby RJ, Bellanova M, Belluzzi A. How to predict clinical relapse in inflammatory bowel disease patients. World J Gastroenterol 2016; 22:1017-1033. [PMID: 26811644 PMCID: PMC4716017 DOI: 10.3748/wjg.v22.i3.1017] [Citation(s) in RCA: 100] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2015] [Revised: 07/07/2015] [Accepted: 11/09/2015] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases have a natural course characterized by alternating periods of remission and relapse. Disease flares occur in a random way and are currently unpredictable for the most part. Predictors of benign or unfavourable clinical course are required to facilitate treatment decisions and to avoid overtreatment. The present article provides a literature review of the current evidence on the main clinical, genetic, endoscopic, histologic, serologic and fecal markers to predict aggressiveness of inflammatory bowel disease and discuss their prognostic role, both in Crohn’s disease and ulcerative colitis. No single marker seems to be reliable alone as a flare predictor, even in light of promising evidence regarding the role of fecal markers, in particular fecal calprotectin, which has reported good results recently. In order to improve our daily clinical practice, validated prognostic scores should be elaborated, integrating clinical and biological markers of prognosis. Finally, we propose an algorithm considering clinical history and biological markers to intercept patients with high risk of clinical relapse.
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Ding NS, Hart A, De Cruz P. Systematic review: predicting and optimising response to anti-TNF therapy in Crohn's disease - algorithm for practical management. Aliment Pharmacol Ther 2016; 43:30-51. [PMID: 26515897 DOI: 10.1111/apt.13445] [Citation(s) in RCA: 230] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2015] [Revised: 09/02/2015] [Accepted: 10/05/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Nonresponse and loss of response to anti-TNF therapies in Crohn's disease represent significant clinical problems for which clear management guidelines are lacking. AIM To review the incidence, mechanisms and predictors of primary nonresponse and secondary loss of response to formulate practical clinical algorithms to guide management. METHODS Through a systematic literature review, 503 articles were identified which fit the inclusion criteria. RESULTS Primary nonresponse to anti-TNF treatment affects 13-40% of patients. Secondary loss of response to anti-TNF occurs in 23-46% of patients when determined according to dose intensification, and 5-13% of patients when gauged by drug discontinuation rates. Recent evidence suggests that the mechanisms underlying primary nonresponse and secondary loss of response are multifactorial and include disease characteristics (phenotype, location, severity); drug (pharmacokinetic, pharmacodynamic or immunogenicity) and treatment strategy (dosing regimen) related factors. Clinical algorithms that employ therapeutic drug monitoring (using anti-TNF tough levels and anti-drug antibody levels) may be used to determine the underlying cause of primary nonresponse and secondary loss of response respectively and guide clinicians as to which patients are most likely to respond to anti-TNF therapy and help optimise drug therapy for those who are losing response to anti-TNF therapy. CONCLUSIONS Nonresponse or loss of response to anti-TNF occurs commonly in Crohn's disease. Clinical algorithms utilising therapeutic drug monitoring may establish the mechanisms for treatment failure and help guide the subsequent therapeutic approach.
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Affiliation(s)
- N S Ding
- Department of Gastroenterology, St Mark's Hospital, Harrow, UK.,Department of Medicine, Imperial College London, London, UK.,Department of Medicine, University of Melbourne, Melbourne, Vic., Australia
| | - A Hart
- Department of Gastroenterology, St Mark's Hospital, Harrow, UK.,Department of Medicine, Imperial College London, London, UK
| | - P De Cruz
- Department of Medicine, University of Melbourne, Melbourne, Vic., Australia.,Department of Gastroenterology, Austin Health, Melbourne, Vic., Australia
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