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Cosier D, Lambert K, Charlton K, Batterham M, Little RD, Wu N, Tavakoli P, Ghaly S, Pipicella JL, Connor S, Leach S, Lemberg DA, Houshyar Y, Jayawardana T, Koentgen S, on behalf of the Australian IBD Microbiome Study Consortium, Hold GL. Dietary Patterns and Fibre Intake Are Associated with Disease Activity in Australian Adults with Inflammatory Bowel Disease: An Exploratory Dietary Pattern Analysis. Nutrients 2024; 16:4349. [PMID: 39770970 PMCID: PMC11677955 DOI: 10.3390/nu16244349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 12/10/2024] [Accepted: 12/12/2024] [Indexed: 01/11/2025] Open
Abstract
BACKGROUND Few studies have explored the relationship between habitual dietary patterns and disease activity in people with Inflammatory Bowel Disease (IBD). This cross-sectional study explored the association between dietary patterns and clinical and objective markers of inflammation in adults from the Australian IBD Microbiome Study. METHODS Dietary patterns were derived using principal component analysis (PCA) of baseline food frequency questionnaire data. Food intake was quantified using 3-day food record data. Associations between dietary intake and both clinical disease activity index (CDAI) and faecal calprotectin (FCP) were analysed. RESULTS Participants included 412 adults (IBD = 223, Healthy controls (HC) = 189). Both cohorts consumed poor-quality diets with inadequate servings of most food groups compared to Australian reference standards. IBD participants without FCP inflammation had significantly higher fibre intake than those with moderate FCP. In the Crohn's Disease group, high adherence to 'High plant diversity' and 'Meat eaters' dietary patterns were associated with increased CDAI and FCP, respectively. In the combined IBD cohort, high adherence to a 'Vegan-style' dietary pattern was associated with increased FCP. CONCLUSIONS There is a need for dietary modifications among Australian adults, both with and without IBD, to improve dietary fibre intake and adherence to dietary guidelines. Dietary patterns characterised by a high intake of plant foods or meat products were both positively associated with indicators of active IBD. It is possible that some participants with active IBD were modifying their diet to try to manage their disease and reduce symptoms, contributing to the association between healthier dietary patterns and active disease. Further clinical and longitudinal studies are needed to expand upon the findings. This study offers a unique contribution by utilising FCP as an objective marker of intestinal inflammation and applying dietary pattern analysis to investigate the relationship between diet and inflammatory markers.
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Affiliation(s)
- Denelle Cosier
- School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Kelly Lambert
- School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Karen Charlton
- School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Marijka Batterham
- Statistical Consulting Centre, National Institute for Applied Statistical Research Australia, University of Wollongong, Wollongong, NSW 2500, Australia
| | - Robert D. Little
- Department of Gastroenterology, Alfred Health, Melbourne, VIC 3004, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3800, Australia
| | - Nan Wu
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
- Department of Gastroenterology, Sutherland Hospital, Sydney, NSW 2229, Australia
| | - Paris Tavakoli
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Simon Ghaly
- Department of Gastroenterology and Hepatology, St Vincent’s Hospital Sydney and St Vincent’s Clinical School, UNSW Medicine & Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Joseph L. Pipicella
- Department of Gastroenterology, Liverpool Hospital and South West Sydney Clinical Campuses, UNSW Medicine & Health, University of New South Wales, Sydney, NSW 2033, Australia
- Crohn’s Colitis Cure, Sydney, NSW 2009, Australia
| | - Susan Connor
- Department of Gastroenterology, Liverpool Hospital and South West Sydney Clinical Campuses, UNSW Medicine & Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Steven Leach
- Discipline of Paediatrics, School of Clinical Medicine, University of New South Wales, Sydney, NSW 2033, Australia
| | - Daniel A. Lemberg
- Discipline of Paediatrics, School of Clinical Medicine, University of New South Wales, Sydney, NSW 2033, Australia
- Department of Gastroenterology, Sydney Children’s Hospital, Sydney, NSW 2031, Australia
| | - Yashar Houshyar
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Thisun Jayawardana
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | - Sabrina Koentgen
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
| | | | - Georgina L. Hold
- University of New South Wales Microbiome Research Centre, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2033, Australia
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Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignass A, Ehehalt R, Germer CT, Grunert PC, Helwig U, Horisberger K, Herrlinger K, Kienle P, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) (Version 4.1) – living guideline. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1229-1318. [PMID: 39111333 DOI: 10.1055/a-2309-6123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Minden, Deutschland
| | - Axel Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | | | - P C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | - Karoline Horisberger
- Universitätsmedizin Johannes Gutenberg, Universität Klinik f. Allgemein-,Visceral- und Transplantationschirurgie, Mainz, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Christian Maaser
- Gastroenterologie, Ambulanzzentrum Lüneburg, Lüneburg, Deutschland
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
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Costa MHDM, Sassaki LY, Chebli JMF. Fecal calprotectin and endoscopic scores: The cornerstones in clinical practice for evaluating mucosal healing in inflammatory bowel disease. World J Gastroenterol 2024; 30:3022-3035. [PMID: 38983953 PMCID: PMC11230062 DOI: 10.3748/wjg.v30.i24.3022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 05/01/2024] [Accepted: 05/27/2024] [Indexed: 06/25/2024] Open
Abstract
Managing inflammatory bowel disease (IBD) is becoming increasingly complex and personalized, considering the advent of new advanced therapies with distinct mechanisms of action. Achieving mucosal healing (MH) is a pivotal therapeutic goal in IBD management and can prevent IBD progression and reduce flares, hospitalization, surgery, intestinal damage, and colorectal cancer. Employing proactive disease and therapy assessment is essential to achieve better control of intestinal inflammation, even if subclinical, to alter the natural course of IBD. Periodic monitoring of fecal calprotectin (FC) levels and interval endoscopic evaluations are cornerstones for evaluating response/remission to advanced therapies targeting IBD, assessing MH, and detecting subclinical recurrence. Here, we comment on the article by Ishida et al Moreover, this editorial aimed to review the role of FC and endoscopic scores in predicting MH in patients with IBD. Furthermore, we intend to present some evidence on the role of these markers in future targets, such as histological and transmural healing. Additional prospective multicenter studies with a stricter MH criterion, standardized endoscopic and histopathological analyses, and virtual chromoscopy, potentially including artificial intelligence and other biomarkers, are desired.
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Affiliation(s)
| | - Ligia Yukie Sassaki
- Department of Internal Medicine, Medical School, São Paulo State University (Unesp), Botucatu 18618-686, São Paulo, Brazil
| | - Júlio Maria Fonseca Chebli
- Division of Gastroenterology, Department of Medicine, University Hospital of The Federal University of Juiz de Fora, University of Juiz de Fora School of Medicine, Juiz de Fora 36036-247, Minas Gerais, Brazil
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Hammoudi N, Sachar D, D'Haens G, Reinisch W, Kotze PG, Vermeire S, Schölmerich J, Kamm MA, Griffiths A, Panes J, Ghosh S, Siegel CA, Bemelman W, O'Morain C, Steinwurz F, Fleshner P, Mantzaris GJ, Sands B, Abreu MT, Dotan I, Turner D, Dignass A, Allez M. Outcomes and Endpoints of Postoperative Recurrence in Crohn's Disease: Systematic Review and Consensus Conference. J Crohns Colitis 2024; 18:943-957. [PMID: 38112601 DOI: 10.1093/ecco-jcc/jjad205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 10/24/2023] [Accepted: 12/01/2023] [Indexed: 12/21/2023]
Abstract
BACKGROUND Outcomes after ileocolonic resection in Crohn's disease [CD] are heterogeneous, and a clear definition of postoperative recurrence remains to be determined. Our Endpoints Working Group of the International Organization for the study of Inflammatory Bowel Disease [IOIBD] aimed to standardise postoperative outcomes, to discuss which endpoints should be used for postoperative clinical trials, and to define those which could be used in trials or registries. METHODS Based on a systematic review of the literature, recommendations and statements were drafted and sent to all IOIBD members for a first round of voting. Recommendations and statements were revised based on the voters' comments during a consensus hybrid conference open to all IOIBD members. If no agreement was reached after two rounds of voting, the statement was excluded. RESULTS In the systematic review, 3071 manuscripts were screened of which 434 were included. Sixteen recommendations were identified, of which 11 were endorsed. Recommendations and statements include that endoscopy remains the gold standard and should be used as a short-term primary endpoint in both observational cohorts and randomised controlled trials. Clinical symptoms classically used in clinical trials for luminal CD are not reliable in this specific situation. For that reason, longer-term endpoints should be based on the evidence of macroscopic inflammation assessed by imaging techniques, endoscopy, or as reflected by the presence of complications. CONCLUSIONS Agencies recommend the use of clinical evaluations, as in the case of luminal CD, and do not recognise primary endpoints based solely on endoscopy. This consensus has led to agreement on the need to define postoperative endoscopy-based and/or imaging-based endpoints.
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Affiliation(s)
- Nassim Hammoudi
- Department of Gastroenterology, Hôpital Saint-Louis, Université Paris Cité, Paris, France
| | - David Sachar
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Geert D'Haens
- Department of Gastroenterology, Amsterdam University Medical Centres, Amsterdam, The Netherlands
| | - Walter Reinisch
- Department Internal Medicine III, Division Gastroenterology & Hepatology, Medical University of Vienna, Vienna, Austria
| | | | - Severine Vermeire
- Department of Gastroenterology & Hepatology, University Hospital Leuven, Leuven, Belgium
| | | | - Michael A Kamm
- Department of Gastroenterology, St Vincent's Hospital, and Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
| | - Anne Griffiths
- IBD Centre, SickKids Hospital, University of Toronto, Toronto, ON, Canada
| | - Julian Panes
- Formerly Department of Gastroenterology, Hospital Clínic de Barcelona, Barcelona, Spain
| | - Subrata Ghosh
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
| | - Corey A Siegel
- IBD Center, Section of Gastroenterology and Hepatology, Dartmouth Hitchcock Medical Center, Lebanon, USA
| | - Willem Bemelman
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Colm O'Morain
- Faculty of Health Sciences, Trinity College Dublin, Dublin, Ireland
| | - Flavio Steinwurz
- Department of Gastroenterology, Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | - Phillip Fleshner
- Division of Colorectal Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | | | - Bruce Sands
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Maria T Abreu
- Department of Medicine, Division of Gastroenterology, Crohn's and Colitis Center, Leonard M. Miller School of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Iris Dotan
- Division of Gastroenterology, Rabin Medica Center, Petah-Tikva, Israel and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Dan Turner
- Juliet Keidan Institute of Pediatric Gastroenterology, Shaare Zedek Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Israel
| | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Goethe-University, Frankfurt Am Main, Germany
| | - Matthieu Allez
- Department of Gastroenterology, Hôpital Saint-Louis, Université Paris Cité, Paris, France
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Edwards TS, Day AS. The role of fecal biomarkers in individuals with inflammatory bowel disease. Expert Rev Mol Diagn 2024; 24:497-508. [PMID: 38995110 DOI: 10.1080/14737159.2024.2375224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 06/28/2024] [Indexed: 07/13/2024]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and Ulcerative Colitis (UC), is a relapsing and remitting condition. Noninvasive biomarkers have an increasingly important role in the diagnosis of IBD and in the prediction of future disease course in individuals with IBD. Strategies for the management of IBD increasingly rely upon close monitoring of gastrointestinal inflammation. AREAS COVERED This review provides an update on the current understanding of established and novel stool-based biomarkers in the diagnosis and management of IBD. It also highlights key gaps, identifies limitations, and advantages of current markers, and examines aspects that require further study and analysis. EXPERT OPINION Current noninvasive inflammatory markers play an important role in the diagnosis and management of IBD; however, limitations exist. Future work is required to further characterize and validate current and novel markers of inflammation. In addition, it is essential to better understand the roles and characteristics of noninvasive markers to enable the appropriate selection to accurately determine the condition of the intestinal mucosa.
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Affiliation(s)
- Teagan S Edwards
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
| | - Andrew S Day
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
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Wiley JW, Higgins GA. Epigenomics and the Brain-gut Axis: Impact of Adverse Childhood Experiences and Therapeutic Challenges. JOURNAL OF TRANSLATIONAL GASTROENTEROLOGY 2024; 2:125-130. [PMID: 40012740 PMCID: PMC11864786 DOI: 10.14218/jtg.2024.00017] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/28/2025]
Abstract
The brain-gut axis represents a bidirectional communication network that integrates neural, hormonal, and immunological signaling between the central nervous system and the gastrointestinal tract. Adverse childhood experiences (ACEs) have increasingly been recognized for their profound impact on this axis, with implications for both mental and physical health outcomes. This mini-review explores the emerging field of epigenomics-specifically, how epigenetic modifications incurred by ACEs can influence the brain-gut axis and contribute to the pathophysiology of various disorders. We examine the evidence linking epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs to the modulation of gene expression involved in stress responses, neurodevelopment, and immune function-all of which intersect at the brain-gut axis. Additionally, we discuss the emerging potential of the gut microbiome as both a target and mediator of epigenetic changes, further influencing brain-gut communication in the context of ACEs. The methodological and therapeutic challenges posed by these insights are significant. The reversibility of epigenetic marks and the long-term consequences of early life stress require innovative and comprehensive approaches to intervention. This underscores the need for comprehensive strategies encompassing psychosocial, pharmacological, neuromodulation, and lifestyle interventions tailored to address ACEs' individualized and persistent effects. Future directions call for a multi-disciplinary approach and longitudinal studies to uncover the full extent of ACEs' impact on epigenetic regulation and the brain-gut axis, with the goal of developing targeted therapies to mitigate the long-lasting effects on health.
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Affiliation(s)
- John W. Wiley
- Department of Internal Medicine, University of Michigan Medicine, Ann Arbor, MI, USA
| | - Gerald A. Higgins
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA
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Kumar M, Murugesan S, Ibrahim N, Elawad M, Al Khodor S. Predictive biomarkers for anti-TNF alpha therapy in IBD patients. J Transl Med 2024; 22:284. [PMID: 38493113 PMCID: PMC10943853 DOI: 10.1186/s12967-024-05058-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 03/04/2024] [Indexed: 03/18/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition characterized by severe gut inflammation, commonly presenting as Crohn's disease, ulcerative colitis or categorized as IBD- unclassified. While various treatments have demonstrated efficacy in adult IBD patients, the advent of anti-TNF therapies has significantly revolutionized treatment outcomes and clinical management. These therapies have played a pivotal role in achieving clinical and endoscopic remission, promoting mucosal healing, averting disease progression, and diminishing the necessity for surgery. Nevertheless, not all patients exhibit positive responses to these therapies, and some may experience a loss of responsiveness over time. This review aims to present a comprehensive examination of predictive biomarkers for monitoring the therapeutic response to anti-TNF therapy in IBD patients. It will explore their limitations and clinical utilities, paving the way for a more personalized and effective therapeutic approach.
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Affiliation(s)
- Manoj Kumar
- Research Department, Sidra Medicine, Doha, Qatar
| | | | - Nazira Ibrahim
- Division of Gastroenterology, Hepatology and Nutrition, Sidra Medicine, Doha, Qatar
| | - Mamoun Elawad
- Division of Gastroenterology, Hepatology and Nutrition, Sidra Medicine, Doha, Qatar
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Fasulo E, D’Amico F, Osorio L, Allocca M, Fiorino G, Zilli A, Parigi TL, Danese S, Furfaro F. The Management of Postoperative Recurrence in Crohn's Disease. J Clin Med 2023; 13:119. [PMID: 38202126 PMCID: PMC10779955 DOI: 10.3390/jcm13010119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 12/20/2023] [Accepted: 12/23/2023] [Indexed: 01/12/2024] Open
Abstract
Crohn's disease (CD) is a chronic inflammatory bowel disease with different phenotypes of presentation, inflammatory, penetrating, or stricturing disease, that significantly impacts patient well-being and quality of life. Despite advances in medical therapy, surgery sometimes represents the only treatment to address complications, such as strictures, fistulas, or abscesses. Minimizing postoperative recurrence (POR) remains a major challenge for both clinicians and patients; consequently, various therapeutic strategies have been developed to prevent or delay POR. The current review outlines an updated overview of POR management. We focused on diagnostic assessment, which included endoscopic examination, biochemical analyses, and cross-sectional imaging techniques, all crucial tools used to accurately diagnose this condition. Additionally, we delved into the associated risk factors contributing to POR development. Furthermore, we examined recent advances in the prophylaxis and treatment of POR in CD.
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Affiliation(s)
- Ernesto Fasulo
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
| | - Ferdinando D’Amico
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20089 Milan, Italy
| | - Laura Osorio
- Gastroenterologist Hospital Pablo Tobon Uribe, Medellín 050010, Colombia;
| | - Mariangela Allocca
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
| | - Gionata Fiorino
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
| | - Alessandra Zilli
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
| | - Silvio Danese
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
- Gastroenterology and Gastrointestinal Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Gastrointestinal Endoscopy, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; (E.F.); (F.D.); (M.A.); (G.F.); (A.Z.); (S.D.)
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9
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Dragoni G, Allocca M, Myrelid P, Noor NM, Hammoudi N, Rivière P, Panis Y, Ferrante M. Results of the Eighth Scientific Workshop of ECCO: Diagnosing Postoperative Recurrence of Crohn's Disease After an Ileocolonic Resection With Ileocolonic Anastomosis. J Crohns Colitis 2023; 17:1373-1386. [PMID: 37070339 DOI: 10.1093/ecco-jcc/jjad055] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Indexed: 04/19/2023]
Abstract
Despite the introduction of potent biologic therapies, many patients with Crohn's disease [CD] still require an ileocolonic resection [ICR] during the course of their disease. Furthermore, the need of redo ICR has not decreased over the past few decades, highlighting the need for better strategies to prevent and treat postoperative recurrence [POR]. The first step to develop such a strategy would be to define and standardise the description of POR with adequate diagnostic instruments. In this article, we will describe the different methodologies used to report POR [endoscopic, histological, radiological, biochemical, clinical, and surgical], and review their potential benefits and limitations, as well as the optimal timing of evaluation.
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Affiliation(s)
- Gabriele Dragoni
- IBD Referral Center, Department of Gastroenterology, Careggi University Hospital, Florence, Italy
- Gastroenterology Research Unit, Department of Experimental and Clinical Biochemical Sciences 'Mario Serio', University of Florence, Florence, Italy
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy
| | - Pär Myrelid
- Department of Surgery, Linköping University Hospital and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Nurulamin M Noor
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Nassim Hammoudi
- Gastroenterology Department, Hôpital Saint-Louis - APHP, Université Paris Cité, INSERM U1160, Paris, France
| | - Pauline Rivière
- Department of Gastroenterology and Hepatology, Centre Médico-chirurgical Magellan, Hôpital Haut-Lévêque, CHU de Bordeaux, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | - Yves Panis
- Paris IBD Center, Groupe Hospitalier Privé Ambroise Paré-Hartmann, Neuilly/Seine, France
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Translational Research in Gastrointestinal Disorders [TARGID], Department of Chronic Diseases and Metabolism [CHROMETA], KU Leuven, Leuven, Belgium
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Shimoyama T, Yamamoto T, Yoshiyama S, Nishikawa R, Umegae S. Leucine-Rich Alpha-2 Glycoprotein Is a Reliable Serum Biomarker for Evaluating Clinical and Endoscopic Disease Activity in Inflammatory Bowel Disease. Inflamm Bowel Dis 2023; 29:1399-1408. [PMID: 36334015 DOI: 10.1093/ibd/izac230] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Leucine-rich alpha-2 glycoprotein (LRG) is a novel serum biomarker for inflammation in inflammatory bowel disease (IBD). This prospective study aimed to compare the value of LRG with C-reactive protein (CRP) and fecal calprotectin for evaluating clinical and endoscopic disease activity in patients with IBD. METHODS At entry, clinical and endoscopic disease activity was assessed in 267 patients with IBD (ulcerative colitis [UC] 203; Crohn's disease [CD] 64), and the levels of LRG, CRP and fecal calprotectin were measured. The accuracy of the biomarkers for the detection of clinical and endoscopic disease activity was determined by the area under the receiver operating characteristic curve. RESULTS Leucine-rich alpha-2 glycoprotein showed a significant relationship with the clinical and endoscopic severity in both UC and CD (both diseases, P < .0001). In the clinical assessment of UC, the accuracy of LRG was significantly higher than that of CRP (0.73 vs 0.63; P < .001). In the endoscopic assessment of UC, the accuracy of LRG was significantly higher than that of CRP (P = .01), but it was significantly lower than that of fecal calprotectin (P = .009; LRG, 0.80; CRP, 0.72; fecal calprotectin, 0.91). In the clinical and endoscopic assessment of CD, the accuracy was not significantly different between the biomarkers (clinical activity: LRG, 0.71; CRP, 0.64; fecal calprotectin, 0.66; in endoscopic activity: LRG, 0.79; CRP, 0.78; fecal calprotectin, 0.81). CONCLUSIONS Leucine-rich alpha-2 glycoprotein is a reliable serum biomarker for the assessment of clinical and endoscopic disease activity in patients with IBD. It can be an alternative to CRP for the assessment of UC.
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Affiliation(s)
- Takahiro Shimoyama
- Inflammatory Bowel Disease Center, Yokkaichi Hazu Medical Center, Yokkaichi, Mie, Japan
| | - Takayuki Yamamoto
- Inflammatory Bowel Disease Center, Yokkaichi Hazu Medical Center, Yokkaichi, Mie, Japan
| | - Shigeyuki Yoshiyama
- Inflammatory Bowel Disease Center, Yokkaichi Hazu Medical Center, Yokkaichi, Mie, Japan
| | - Ryutaro Nishikawa
- Inflammatory Bowel Disease Center, Yokkaichi Hazu Medical Center, Yokkaichi, Mie, Japan
| | - Satoru Umegae
- Inflammatory Bowel Disease Center, Yokkaichi Hazu Medical Center, Yokkaichi, Mie, Japan
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11
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Li T, Click B, Bachour S, Sachs M, Barnes EL, Cohen BL, Contreras S, Axelrad J. Suboptimal Guideline Adherence and Biomarker Underutilization in Monitoring of Post-operative Crohn's Disease. Dig Dis Sci 2023; 68:3596-3604. [PMID: 37548896 DOI: 10.1007/s10620-023-08044-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 07/13/2023] [Indexed: 08/08/2023]
Abstract
BACKGROUND Crohn's disease recurrence after ileocecal resection is common. Guidelines suggest colonoscopy within 6-12 months of surgery to assess for post-operative recurrence, but use of adjunctive monitoring is not protocolized. We aimed to describe the state of monitoring in post-operative Crohn's. METHODS We conducted a retrospective study of patients with Crohn's after ileocolic resection with ≥ 1-year follow-up. Patients were stratified into high and low risk based on guidelines. Post-operative biomarker (C-reactive protein, fecal calprotectin), cross-sectional imaging, and colonoscopy use were assessed. Biomarker, radiographic, and endoscopic post-operative recurrence were defined as elevated CRP/calprotectin, active inflammation on imaging, and Rutgeerts ≥ i2b, respectively. Data were stratified by surgery year to assess changes in practice patterns over time. P-values were calculated using Wilcoxon test and Fisher exact test. RESULTS Of 901 patients, 53% were female and 78% high risk. Median follow-up time was 60 m for LR and 50 m for high risk. Postoperatively, 18% low and 38% high risk had CRPs, 5% low and 10% high risk had calprotectins, and half of low and high risk had cross-sectional imaging. 29% low and 38% high risk had colonoscopy by 1 year. Compared to pre-2015, time to first radiography (584 days vs. 398 days) and colonoscopy (421 days vs. 296 days) were significantly shorter for high-risk post-2015 (P < 0.001). Probability of colonoscopy within 1 year increased over time (0.48, 2011 vs. 0.92, 2019). CONCLUSION Post-operative colonoscopy completion by 1 year is low. The use of CRP and imaging are common, whereas calprotectin is infrequently utilized. Practice patterns are shifting toward earlier monitoring.
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Affiliation(s)
- Terry Li
- Department of Internal Medicine, NYU Grossman School of Medicine, New York University Langone Health, 550 First Avenue, New York, NY, USA.
| | - Benjamin Click
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Salam Bachour
- Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Michael Sachs
- Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark
| | - Edward L Barnes
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Benjamin L Cohen
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH, USA
| | - Susell Contreras
- Inflammatory Bowel Disease Center, New York University Langone Health, New York, NY, USA
| | - Jordan Axelrad
- Inflammatory Bowel Disease Center, New York University Langone Health, New York, NY, USA
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12
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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: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [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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13
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Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignaß A, Ehehalt R, Germer C, Grunert PC, Helwig U, Herrlinger K, Kienle P, Kreis ME, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – August 2021 – AWMF-Registernummer: 021-004. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:332-418. [PMID: 35263784 DOI: 10.1055/a-1713-3941] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Axel Dignaß
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Christoph Germer
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Deutschland
| | - Philip C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Martin E Kreis
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | | | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
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14
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Veyre F, Boschetti G, Meunier C, Cuerq C, Gay C, Charlois AL, Duclaux-Loras R, Danion P, Cotte E, Kepenekian V, Mialon A, Faure M, Roblin X, Flourie B, Nancey S. Low Levels of Fecal Calprotectin 3 Months After Surgery Predict Subsequent Endoscopic Postoperative Remission in Crohn's Disease. Dig Dis Sci 2021; 66:4429-4435. [PMID: 33387123 DOI: 10.1007/s10620-020-06751-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Accepted: 11/25/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS In Crohn's disease (CD) few data are available on the usefulness of monitoring fecal calprotectin (FC) in the early postoperative setting. We assessed prospectively the accuracy of FC measured 3 months after surgery to predict the risk of endoscopic postoperative recurrence (POR) within 1 year after resection. METHODS In 55 consecutive CD patients who had undergone ileocolonic resection samples were collected 3 months after surgery for measuring serum CRP and FC. Endoscopic POR was assessed by ileocolonoscopy within 6-12 months (median 7 months). Receiver operating characteristic (ROC) curves were generated to assess accuracy of the markers, to determine the best threshold and to calculate sensitivity, specificity, positive and negative predictive values. RESULTS In contrast with median CRP levels, median FC concentrations measured 3 months after surgery were significantly higher in patients who later experienced endoscopic POR (Rutgeerts ≥ i2) compared with those who stayed in endoscopic remission within the following 6-12 months (205 μg/g IQR [106-721] vs. 103 μg/g IQR [60-219], p = 0.008). Area under the ROC curve for FC was 0.71. The best cutoff value of FC to identify patients in subsequent endoscopic remission 3 months after surgery was 65 μg/g (96% sensitivity, 31% specificity, 50% positive and 91% negative predictive values). In multivariate analysis, FC < 65 µg/g at 3 months was the only factor associated with subsequent endoscopic remission. CONCLUSION FC measured 3 months after surgery below 65 μg/g is an accurate marker to identify CD patients who will later stay in endoscopic remission within 1 year after resection.
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Affiliation(s)
- Florian Veyre
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud University Hospital, 165 Chemin du Grand Revoyet, 69495, Pierre Benite, France
| | - Gilles Boschetti
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud University Hospital, 165 Chemin du Grand Revoyet, 69495, Pierre Benite, France
- CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France
- Equipe Labellisée par la Fondation pour la Recherche Médicale, FRM, Montpellier, France
| | - Camille Meunier
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud University Hospital, 165 Chemin du Grand Revoyet, 69495, Pierre Benite, France
| | - Charlotte Cuerq
- Laboratory of Biochemistry, Hospices Civils de Lyon, Lyon-Sud University Hospital, Pierre-Bénite, France
| | - Claire Gay
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud University Hospital, 165 Chemin du Grand Revoyet, 69495, Pierre Benite, France
| | - Anne-Laure Charlois
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud University Hospital, 165 Chemin du Grand Revoyet, 69495, Pierre Benite, France
| | - Remi Duclaux-Loras
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud University Hospital, 165 Chemin du Grand Revoyet, 69495, Pierre Benite, France
- CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France
- Equipe Labellisée par la Fondation pour la Recherche Médicale, FRM, Montpellier, France
| | - Pauline Danion
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud University Hospital, 165 Chemin du Grand Revoyet, 69495, Pierre Benite, France
| | - Eddy Cotte
- Department of Surgery, Hospices Civils de Lyon, Lyon-Sud University Hospital, Pierre-Bénite, France
| | - Vahan Kepenekian
- Department of Surgery, Hospices Civils de Lyon, Lyon-Sud University Hospital, Pierre-Bénite, France
| | - Anne Mialon
- Laboratory of Biochemistry, Hospices Civils de Lyon, Lyon-Sud University Hospital, Pierre-Bénite, France
| | - Mathias Faure
- CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France
- Equipe Labellisée par la Fondation pour la Recherche Médicale, FRM, Montpellier, France
| | - Xavier Roblin
- Department of Gastroenterology, EA-30 64, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Faculty of Medicine of Saint-Etienne, Saint-Etienne University Hospital, Saint-Etienne, France
| | - Bernard Flourie
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud University Hospital, 165 Chemin du Grand Revoyet, 69495, Pierre Benite, France
- CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France
- Equipe Labellisée par la Fondation pour la Recherche Médicale, FRM, Montpellier, France
| | - Stéphane Nancey
- Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud University Hospital, 165 Chemin du Grand Revoyet, 69495, Pierre Benite, France.
- CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.
- Equipe Labellisée par la Fondation pour la Recherche Médicale, FRM, Montpellier, France.
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15
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Vernia F, Viscido A, Di Ruscio M, Stefanelli G, Valvano M, Latella G. Fecal Lactoferrin and Other Putative Fecal Biomarkers in Crohn's Disease: Do They Still Have a Potential Clinical Role? Digestion 2021; 102:833-844. [PMID: 34518458 DOI: 10.1159/000518419] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 07/11/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several limits, is fecal calprotectin. This review aims to elucidate the role, if any, of all other fecal biomarkers, as alternative tools for assessing clinical and endoscopic disease activity, and predict capsule endoscopy findings, response to therapy, disease relapse, and postoperative recurrence. These fecal biomarkers included lactoferrin, S100A12, high mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, lysozyme, human beta-defensin-2, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, chitinase 3-like-1, M2-pyruvate kinase, myeloperoxidase, and eosinophil proteins. METHODS A systematic electronic search in the medical literature was performed up to April 2020. Seventy eligible studies were identified out of 859 citations. Data were grouped according to the assessment of clinical and endoscopic disease activity, capsule endoscopy findings, response to therapy, prediction of relapse, and postoperative recurrence. RESULTS The overall correlation between lactoferrin and clinical indexes is poor, while performance is good with endoscopic scores. Lactoferrin seems to represent a reasonably good surrogate marker of response to therapy and to be potentially useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence. The evaluation of the performance of all other fecal markers is limited by the lack of adequate data. CONCLUSIONS None of the fecal markers so far represents an acceptable alternative to calprotectin in clinical practice. Fecal lactoferrin is the only possible exception, but a more extensive investigation is still required.
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Affiliation(s)
- Filippo Vernia
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Angelo Viscido
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Mirko Di Ruscio
- IBD Unit of IRCCS Ospedale Sacro Cuore - Don Calabria, Verona, Italy
| | - Gianpiero Stefanelli
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Marco Valvano
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Giovanni Latella
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
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16
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Primas C, Hopf G, Reinisch S, Baumann L, Novacek G, Reinisch W, Vogelsang H. Role of fecal calprotection in predicting endoscopic recurrence in postoperative Crohn's disease. Scand J Gastroenterol 2021; 56:1169-1174. [PMID: 34314308 DOI: 10.1080/00365521.2021.1955965] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [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 (fCP) has been shown to correlate with endoscopic disease activity in Crohn's disease (CD). The aim of this study was to evaluate its role in predicting early endoscopic recurrence in postoperative CD. METHODS Patients who underwent CD-related intestinal resection with ileocolonic anastomosis were prospectively followed up until ileocolonoscopy was performed around 12 months post-surgery. Endoscopic recurrence (ER) was defined as modified Rutgeerts score i2b or higher. Endoscopic still images were reviewed by 2 independent reviewers blinded to fCP results. Stool specimens were collected 6 months post-surgery and a multivariate logistic regression model was established to explore the predictive value of fCP for ER. RESULTS 79 patients were included. FCP was significantly associated with endoscopic recurrence (p = .036). A cut-off value of fCP of 267 µg/g at 6 months post-surgery predicted ER with a sensitivity of 61.8% and a specificity of 72.7% (AUC 0.669). A prediction model subsuming age at diagnosis and fCP 6 months post-surgery were significantly associated with ER (fCP at 6 months [p = .007] and age at diagnosis [p = .004], multivariate analysis). CONCLUSIONS FCP 6 months after surgery and age at diagnosis predict early ER at 1 year postoperatively. However, the low sensitivity of fCP still suggests the necessity of endoscopy as a gold standard for the assessment of postoperative recurrence of CD.KEY SUMMARYWhat is already known? Fecal calprotectin (fCP) correlates with endoscopic disease activity. Endoscopic recurrence occurs in up to 70% of patients after intestinal resection within 1 year.What are the significant and/or new findings of this study? Fecal calprotectin 6 months post-surgery and age at diagnosis significantly predict endoscopic recurrence at 1 year. Due to low sensitivity fCP cannot replace the necessity of endoscopy for accurate assessment of postoperative recurrence.
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Affiliation(s)
- Christian Primas
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Gertrud Hopf
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Sieglinde Reinisch
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Lukas Baumann
- Section for Medical Statistics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria
| | - Gottfried Novacek
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Walter Reinisch
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Harald Vogelsang
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
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17
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Hedin CRH, Sonkoly E, Eberhardson M, Ståhle M. Inflammatory bowel disease and psoriasis: modernizing the multidisciplinary approach. J Intern Med 2021; 290:257-278. [PMID: 33942408 DOI: 10.1111/joim.13282] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 01/11/2021] [Accepted: 01/18/2021] [Indexed: 12/11/2022]
Abstract
Psoriasis and inflammatory bowel disease (IBD) are immune-mediated diseases occurring in barrier organs whose main task is to protect the organism from attack. These disorders are highly prevalent especially in northern Europe where psoriasis has a prevalence of around 3-4% and IBD around 0.3%. The prevalence of IBD in North America has been estimated at around 0.4%. The total incidence rates in northern Europe have been estimated at around 6 for Crohn's disease and 11 for ulcerative colitis per 100 000 person-years, compared with an incidence rate of around 280 per 100 000 person-years for psoriasis. Both diseases are less common in countries with a lower index of development. The rise in IBD appears to occur as populations adopt a westernized lifestyle, whereas psoriasis seems more stable and prevalence differences may derive more from variation in genetic susceptibility. The gut microbiota is clearly an important driver of IBD pathogenesis; in psoriasis, changes in gut and skin microbiota have been reported, but it is less clear whether and how these changes contribute to the pathogenesis. Large studies show that most identified genes are involved in the immune system. However, psoriasis and IBD are highly heterogeneous diseases and there is a need for more precise and deeper phenotyping to identify specific subgroups and their genetic, epigenetic and molecular signatures. Epigenetic modifications of DNA such as histone modifications, noncoding RNA effects on transcription and translation and DNA methylation are increasingly recognized as the mechanism underpinning much of the gene-environment interaction in the pathogenesis of both IBD and psoriasis. Our understanding of underlying pathogenetic mechanisms has deepened fundamentally over the past decades developing hand in hand with novel therapies targeting pathways and proinflammatory cytokines incriminated in disease. There is not only substantial overlap between psoriasis and IBD, but also there are differences with implication for therapy. In psoriasis, drugs targeting interleukin-23 and interleukin-17 have shown superior efficacy compared with anti-TNFs, whilst in IBD, drugs targeting interleukin-17 may be less beneficial. The therapeutic toolbox for psoriasis is impressive and is enlarging also for IBD. Still, there are unmet needs reflecting the heterogeneity of both diseases and there is a need for closer molecular diagnostics to allow for the development of precise therapeutics.
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Affiliation(s)
- C R H Hedin
- From the, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.,Division of Gastroenterology, Medical Unit Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - E Sonkoly
- From the, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.,Division of Dermatology, Medical Unit Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - M Eberhardson
- From the, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.,Department of Gastroenterology, University Hospital in Linkoping, Linkoping, Sweden
| | - M Ståhle
- From the, Department of Medicine, Karolinska Institutet, Solna, Stockholm, Sweden.,Division of Dermatology, Medical Unit Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
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18
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Etiology of Colitis-Complex Diarrhea in Growing Pigs: A Review. Animals (Basel) 2021; 11:ani11072151. [PMID: 34359279 PMCID: PMC8300613 DOI: 10.3390/ani11072151] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 07/13/2021] [Accepted: 07/14/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Diarrhea in growing pigs is a challenge for the pig industry since it is associated with reduced animal welfare, retarded growth, increased feed conversion ratio, and is often treated with antibiotics. One of the major causes of diarrhea in the growing period is large intestinal inflammation, often referred to as colitis. The exact causes of colitis-complex diarrhea are still to be understood, but dietary factors and/or pathogens have been recognized as the major factors in developing colitis-complex diarrhea. In this review, a thorough picture of pathogens, dietary factors, and a number of possible biomarkers related to colitis-complex diarrhea is presented. Abstract Colitis-complex diarrhea (CCD) in pigs can be defined as a type of diarrhea, which is associated with colonic inflammation and disrupted colonic gut barrier functionality in growing pigs (4–16 weeks post-weaning). It is a challenge for the pig industry as it is associated with the high use of antibiotics, reduced animal welfare, and depressed growth rate. The exact etiology of CCD is still unclear; however, pathogens including Brachyspira (B.) hyodysenteriae, B. pilosicoli, and swine whipworms such as Trichuris (T.) suis have been involved in specific colitis (SC). In the absence of specific pathogens, dietary factors, such as high levels of protein, pelleted feedstuffs, and lack of sufficient antioxidants, can result in non-specific colitis (NSC). On the other hand, supplement of polyunsaturated fatty acids (PUFA) and polyphenols, sufficient supply of essential amino acids (e.g., threonine, cysteine, and proline), short-chain fatty acids (SCFA; especially butyrate), and resistant starch have shown to confer preventing/ameliorating effects on CCD. Different putative biomarkers associated with CCD have been presented. It is anticipated that a comprehensive picture of the possible causes of CCD and potential dietary interventions could cast light on the direction of future studies aimed at developing preventive and curative strategies against CCD in growing pigs.
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Lo Sasso G, Khachatryan L, Kondylis A, Battey JND, Sierro N, Danilova NA, Grigoryeva TV, Markelova MI, Khusnutdinova DR, Laikov AV, Salafutdinov II, Romanova YD, Siniagina MN, Vasiliev IY, Boulygina EA, Solovyeva VV, Garanina EE, Kitaeva KV, Ivanov KY, Chulpanova DS, Kletenkov KS, Valeeva AR, Odintsova AK, Ardatskaya MD, Abdulkhakov RA, Ivanov NV, Peitsch MC, Hoeng J, Abdulkhakov SR. Inflammatory Bowel Disease-Associated Changes in the Gut: Focus on Kazan Patients. Inflamm Bowel Dis 2021; 27:418-433. [PMID: 32766755 PMCID: PMC7885336 DOI: 10.1093/ibd/izaa188] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Several studies have highlighted the role of host-microbiome interactions in the pathogenesis of inflammatory bowel disease (IBD), resulting in an increasing amount of data mainly focusing on Western patients. Because of the increasing prevalence of IBD in newly industrialized countries such as those in Asia, the Middle East, and South America, there is mounting interest in elucidating the gut microbiota of these populations. We present a comprehensive analysis of several IBD-related biomarkers and gut microbiota profiles and functions of a unique population of patients with IBD and healthy patients from Kazan (Republic of Tatarstan, Russia). METHODS Blood and fecal IBD biomarkers, serum cytokines, and fecal short-chain fatty acid (SCFA) content were profiled. Finally, fecal microbiota composition was analyzed by 16S and whole-genome shotgun sequencing. RESULTS Fecal microbiota whole-genome sequencing confirmed the presence of classic IBD dysbiotic features at the phylum level, with increased abundance of Proteobacteria, Actinobacteria, and Fusobacteria and decreased abundance of Firmicutes, Bacteroidetes, and Verrucomicrobia. At the genus level, the abundance of both fermentative (SCFA-producing and hydrogen (H2)-releasing) and hydrogenotrophic (H2-consuming) microbes was affected in patients with IBD. This imbalance was confirmed by the decreased abundance of SCFA species in the feces of patients with IBD and the change in anaerobic index, which mirrors the redox status of the intestine. CONCLUSIONS Our analyses highlighted how IBD-related dysbiotic microbiota-which are generally mainly linked to SCFA imbalance-may affect other important metabolic pathways, such as H2 metabolism, that are critical for host physiology and disease development.
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Affiliation(s)
- Giuseppe Lo Sasso
- Philip Morris International Research and Development, Philip Morris Products S.A., Neuchâtel, Switzerland
| | - Lusine Khachatryan
- Philip Morris International Research and Development, Philip Morris Products S.A., Neuchâtel, Switzerland
| | - Athanasios Kondylis
- Philip Morris International Research and Development, Philip Morris Products S.A., Neuchâtel, Switzerland
| | - James N D Battey
- Philip Morris International Research and Development, Philip Morris Products S.A., Neuchâtel, Switzerland
| | - Nicolas Sierro
- Philip Morris International Research and Development, Philip Morris Products S.A., Neuchâtel, Switzerland
| | - Natalia A Danilova
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Tatiana V Grigoryeva
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Maria I Markelova
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Dilyara R Khusnutdinova
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Alexander V Laikov
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Ilnur I Salafutdinov
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Yulia D Romanova
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Mariia N Siniagina
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Ilya Yu Vasiliev
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Eugenia A Boulygina
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Valeriya V Solovyeva
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Ekaterina E Garanina
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Kristina V Kitaeva
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Konstantin Y Ivanov
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Darja S Chulpanova
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Konstantin S Kletenkov
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
| | - Alina R Valeeva
- Department of Clinical Immunology and Allergology, Kazan State Medical University, Kazan, Tatarstan, Russian Federation
| | - Alfiya Kh Odintsova
- Department of Gastroenterology, Republican Clinical Hospital of Tatarstan Republic, Kazan, Tatarstan, Russian Federation
| | - Maria D Ardatskaya
- Central State Medical Academy of Administrative Department of the President of the Russian Federation, Moscow, Russian Federation
| | - Rustam A Abdulkhakov
- Department of Clinical Immunology and Allergology, Kazan State Medical University, Kazan, Tatarstan, Russian Federation
| | - Nikolai V Ivanov
- Philip Morris International Research and Development, Philip Morris Products S.A., Neuchâtel, Switzerland
| | - Manuel C Peitsch
- Philip Morris International Research and Development, Philip Morris Products S.A., Neuchâtel, Switzerland
| | - Julia Hoeng
- Philip Morris International Research and Development, Philip Morris Products S.A., Neuchâtel, Switzerland
| | - Sayar R Abdulkhakov
- Kazan Federal University, Institute of Fundamental Medicine and Biology, Kazan, Tatarstan, Russian Federation
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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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21
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Asad S, Wegler C, Ahl D, Bergström CAS, Phillipson M, Artursson P, Teleki A. Proteomics-Informed Identification of Luminal Targets For In Situ Diagnosis of Inflammatory Bowel Disease. J Pharm Sci 2020; 110:239-250. [PMID: 33159915 DOI: 10.1016/j.xphs.2020.11.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 11/01/2020] [Accepted: 11/02/2020] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic condition resulting in impaired intestinal homeostasis. Current practices for diagnosis of IBD are challenged by invasive, demanding procedures. We hypothesized that proteomics analysis could provide a powerful tool for identifying clinical biomarkers for non-invasive IBD diagnosis. Here, the global intestinal proteomes from commonly used in vitro and in vivo models of IBD were analyzed to identify apical and luminal proteins that can be targeted by orally delivered diagnostic agents. Global proteomics analysis revealed upregulated plasma membrane proteins in intestinal segments of proximal- and distal colon from dextran sulfate sodium-treated mice and also in inflamed human intestinal Caco-2 cells pretreated with pro-inflammatory agents. The upregulated colon proteins in mice were compared to the proteome of the healthy ileum, to ensure targeting of diagnostic agents to the inflamed colon. Promising target proteins for future investigations of non-invasive diagnosis of IBD were found in both systems and included Tgm2/TGM2, Icam1/ICAM1, Ceacam1/CEACAM1, and Anxa1/ANXA1. Ultimately, these findings will guide the selection of appropriate antibodies for surface functionalization of imaging agents aimed to target inflammatory biomarkers in situ.
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Affiliation(s)
- Shno Asad
- Department of Pharmacy, Science for Life Laboratory, Uppsala University, SE-75123 Uppsala, Sweden
| | - Christine Wegler
- Department of Pharmacy, Uppsala University, SE-75123 Uppsala, Sweden; Department of Pharmacy, Uppsala University Drug Optimization and Pharmaceutical Profiling Platform (UDOPP), SE-75123 Uppsala, Sweden
| | - David Ahl
- Department of Medical Cell Biology, Uppsala University, SE-75123 Uppsala, Sweden
| | - Christel A S Bergström
- Department of Pharmacy, Uppsala University, SE-75123 Uppsala, Sweden; The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, SE-75123 Uppsala, Sweden
| | - Mia Phillipson
- Department of Medical Cell Biology, Uppsala University, SE-75123 Uppsala, Sweden
| | - Per Artursson
- Department of Pharmacy, Uppsala University, SE-75123 Uppsala, Sweden
| | - Alexandra Teleki
- Department of Pharmacy, Science for Life Laboratory, Uppsala University, SE-75123 Uppsala, Sweden.
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22
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Fecal calprotectin: current and future perspectives for inflammatory bowel disease treatment. Eur J Gastroenterol Hepatol 2020; 32:1091-1098. [PMID: 32282400 DOI: 10.1097/meg.0000000000001731] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Fecal calprotectin has been widely studied in inflammatory bowel disease (IBD) under clinical and therapeutic settings. It showed a good correlation with clinical, endoscopic, and histologic findings. For these reasons, fecal calprotectin is currently one of the most useful tools in IBD care, both in diagnosis and in clinical management. The development of biologic drugs allowed a deeper control of disease, which sometimes reaches histological healing; this is associated with a reduced risk of relapses and complications. The management of IBD treatment is currently carried out with a treat-to-target approach, and mucosal healing is considered at present to be the optimal therapeutic target, but the future is going through histologic remission. Fecal calprotectin is probably the best marker of mucosal healing, but it is correlated also with histologic remission: moreover, it has been recently studied as a possible therapeutic target in the CALM study. We carried out a comprehensive literature review in order to evaluate the role of fecal calprotectin at present and in the future in the management of IBD therapies.
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Yamamoto T, Lightner AL, Spinelli A, Kotze PG. Perioperative management of ileocecal Crohn's disease in the current era. Expert Rev Gastroenterol Hepatol 2020; 14:843-855. [PMID: 32729736 DOI: 10.1080/17474124.2020.1802245] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION The ileocecal region is most commonly involved in patients with Crohn's disease (CD). AREAS COVERED In the management of ileocecal CD, this review discusses the underlying clinical issues with perioperative management and surgical intervention. EXPERT OPINION Despite advances in medical treatments, surgery is required in a proportion of patients. Preoperative optimization including weaning of corticosteroids, initiation of enteral feeds, venous thromboembolism prophylaxis and smoking cessation may lead to improved postoperative outcomes. Several surgical approaches regarding anastomotic technique and range of mesentery division are now attempted to reduce the incidence of postoperative recurrence. Disease recurrence is common after surgery for CD. Early endoscopic assessment and subsequent treatment adjustment are optimal strategies for the prevention of recurrence after ileocolonic resection.
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Affiliation(s)
- Takayuki Yamamoto
- Inflammatory Bowel Disease Center & Department of Surgery, Yokkaichi Hazu Medical Center , Yokkaichi, Japan
| | - Amy Lee Lightner
- Department of Colorectal Surgery, Cleveland Clinic Foundation , Cleveland, OH, USA
| | - Antonino Spinelli
- Division of Colon and Rectal Surgery, Humanitas Clinical and Research Center, IRCCS , Rozzano, Italy.,Department of Biomedical Sciences, Humanitas University , Rozzano, Italy
| | - Paulo Gustavo Kotze
- IBD Outpatient Clinics, Colorectal Surgery Unit, Catholic University of Parana (PUCPR) , Curitiba, Brazil
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24
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Dai C, Jiang M, Sun MJ, Cao Q. Fecal Lactoferrin for Assessment of Inflammatory Bowel Disease Activity: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2020; 54:545-553. [PMID: 30994521 DOI: 10.1097/mcg.0000000000001212] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Persistent disease activity is associated with a poor prognosis in inflammatory bowel disease (IBD) patients. Therefore, monitoring of IBD activity can avoid the poor prognosis. Serum biomarkers reflect a summation of systemic host responses rather than being specific for intestinal inflammation. And endoscopic monitoring is invasive, costly, and time consuming. The objective of our study was to perform a meta-analysis evaluating the diagnostic accuracy of fecal lactoferrin (FL) in assessing IBD activity. METHODS We systematically searched the databases from inception to May 2018 that evaluated IBD activity. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. The extracted data were pooled using a summary receiver operating characteristic curve model. Random-effects model was used to summarize the diagnostic odds ratio, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. RESULTS Ten studies comprising 773 IBD patients were included in the meta-analysis. The pooled sensitivity and specificity values for assessing ulcerative colitis (UC) activity were 0.81 [95% confidence interval (CI), 0.64-0.92] and 0.82 (95% CI, 0.61-0.93), respectively. And the pooled sensitivity and specificity values for assessing Crohn's disease (CD) activity were 0.82 (95% CI, 0.73-0.88) and 0.71 (95% CI, 0.63-0.78), respectively. The diagnostic performance of the FL assay in the UC patients appeared to be superior to that in the CD patients. CONCLUSION Our meta-analysis has found that FL is an inexpensive, simple, stable, and useful screening marker with high sensitivity and modest specificity for assessing IBD activity, appearing to have greater ability to evaluate UC rather than CD.
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Affiliation(s)
- Cong Dai
- Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China
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25
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Optimal strategies to prevent recrudescent Crohn's disease after resection. SEMINARS IN COLON AND RECTAL SURGERY 2020. [DOI: 10.1016/j.scrs.2020.100746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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26
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Gottlieb ZS, Ungaro R. Could a Blood Marker of T-Cell Exhaustion be Inflammatory Bowel Disease's New Crystal Ball? Gastroenterology 2020; 158:1168-1170. [PMID: 31954112 PMCID: PMC7062560 DOI: 10.1053/j.gastro.2020.01.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Indexed: 12/02/2022]
Affiliation(s)
- Zoë S. Gottlieb
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Ryan Ungaro
- The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
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27
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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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28
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Cerrillo E, Moret I, Iborra M, Pamies J, Hervás D, Tortosa L, Sáez-González E, Nos P, Beltrán B. A Nomogram Combining Fecal Calprotectin Levels and Plasma Cytokine Profiles for Individual Prediction of Postoperative Crohn's Disease Recurrence. Inflamm Bowel Dis 2019; 25:1681-1691. [PMID: 30925193 DOI: 10.1093/ibd/izz053] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The aims of this study were to characterize the immune response profile in patients with Crohn's disease (CD) and early postoperative recurrence (POR), to identify predictive biomarkers, and to develop a noninvasive predictive tool for individual estimation of POR risk. METHODS Sixty-one patients who had undergone ileocolonic resection for CD were prospectively included and followed up for 24 months. Fecal calprotectin (FC), analytical parameters, and plasma cytokines were obtained before surgery and at various time points during postoperative follow-up. Morphological recurrence was assessed by ileocolonoscopy or magnetic resonance enterography within 6-12 months after surgery. Clinical activity was scored using the Harvey-Bradshaw Index. RESULTS Twenty-seven patients (44.3%) had morphological recurrence during follow-up. Fecal calprotectin values were significantly associated with POR risk over time. The receiver operating characteristic curve for FC provided an area under the curve (AUC) of 0.88 (95% confidence interval, 0.75-0.96), and morphological recurrence was best predicted by FC ≥160 μg/g at 6 months after surgery (85% sensitivity, 70% specificity, 26% predictive positive value, 98% negative predictive value [NPV]). The plasma cytokine profile showed higher presurgery interleukin (IL)-13 plasma levels and higher IL-6 and interferon (IFN)-γ levels at 6 months after surgery in patients with POR compared with patients without recurrence. The combination of FC, IL-6, and IFN-γ values at 6 months gave an AUC of 0.90 for predicting an early recurrence. CONCLUSIONS FC values <160 μg/g at 6 months have a high NPV to rule out early lesions. Combined values of FC, IL-6, and IFN-γ levels at 6 months postsurgery constitute a prognostic index with a high predictive capacity to assess the risk of early POR.
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Affiliation(s)
- Elena Cerrillo
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - Inés Moret
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - Marisa Iborra
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - José Pamies
- Radiology Department, La Fe University and Polytechnic Hospital, Valencia, Spain
| | - David Hervás
- Biostatistics Unit, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
| | - Luis Tortosa
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
| | - Esteban Sáez-González
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
| | - Pilar Nos
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
| | - Belén Beltrán
- Inflammatory Bowel Disease Unit, Gastroenterology Department, La Fe University and Polytechnic Hospital, Valencia, Spain.,Inflammatory Bowel Disease Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.,Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III, Madrid, Spain
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29
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Maaser C, Sturm A, Vavricka SR, Kucharzik T, Fiorino G, Annese V, Calabrese E, Baumgart DC, Bettenworth D, Borralho Nunes P, Burisch J, Castiglione F, Eliakim R, Ellul P, González-Lama Y, Gordon H, Halligan S, Katsanos K, Kopylov U, Kotze PG, Krustinš E, Laghi A, Limdi JK, Rieder F, Rimola J, Taylor SA, Tolan D, van Rheenen P, Verstockt B, Stoker J. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis 2019; 13:144-164. [PMID: 30137275 DOI: 10.1093/ecco-jcc/jjy113] [Citation(s) in RCA: 1117] [Impact Index Per Article: 186.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Christian Maaser
- Outpatients Department of Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | - Andreas Sturm
- Department of Gastroenterology, DRK Kliniken Berlin I Westend, Berlin, Germany
| | | | - Torsten Kucharzik
- Department of Internal Medicine and Gastroenterology, Hospital Lüneburg, Lüneburg, Germany
| | - Gionata Fiorino
- Department of Gastroenterology, Humanitas Clinical and Research Institute, Milan, Italy
| | - Vito Annese
- Department of Gastroenterology, Valiant Clinic & American Hospital, Dubai, UAE
| | - Emma Calabrese
- Department of Systems Medicine, University of Rome, Tor Vergata, Italy
| | - Daniel C Baumgart
- Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada
| | - Dominik Bettenworth
- Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany
| | - Paula Borralho Nunes
- Department of Anatomic Pathology, Hospital Cuf Descobertas; Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital; Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark
| | - Fabiana Castiglione
- Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Rami Eliakim
- Department of Gastroenterology, Sheba Medical Center, Sackler School of Medicine, Tel Aviv, Israel
| | - Pierre Ellul
- Department of Medicine, Mater Dei Hospital, Msida, Malta
| | - Yago González-Lama
- Department of Gastroenterology, University Hospital Puerta De Hierro, Majadahonda [Madrid], Spain
| | - Hannah Gordon
- Department of Gastroenterology, Royal London Hospital, London, UK
| | - Steve Halligan
- Centre for Medical Imaging, University College London, London, UK
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center, Sackler School of Medicine, Tel Aviv, Israel
| | - Paulo G Kotze
- Colorectal Surgery Unit, Catholic University of Paraná [PUCPR], Curitiba, Brazil
| | - Eduards Krustinš
- Department of of Gastroenterology, Hepatology and Nutrition, Pauls Stradins Clinical University Hospital, Riga, Latvia
| | - Andrea Laghi
- Department of Clinical and Surgical Translational Medicine, Sapienza University of Rome, Rome, Italy
| | - Jimmy K Limdi
- Department of Gastroenterology, Pennine Acute Hospitals NHS Trust, Manchester; Manchester Academic Health Sciences Centre, University of Manchester, UK
| | - Florian Rieder
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Jordi Rimola
- Department of Radiology, Hospital Clínic Barcelona, Barcelona, Spain
| | - Stuart A Taylor
- Centre for Medical Imaging, University College London, London, UK
| | - Damian Tolan
- Clinical Radiology, St James's University Hospital, Leeds, UK
| | - Patrick van Rheenen
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, University Medical Center Groningen, Groningen, The Netherlands
| | - Bram Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven and CHROMETA - Translational Research in Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Jaap Stoker
- Department of Radiology and Nuclear Medicine, Academic Medical Center [AMC], University of Amsterdam, Amsterdam, The Netherlands
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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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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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Mumolo MG, Bertani L, Ceccarelli L, Laino G, Di Fluri G, Albano E, Tapete G, Costa F. From bench to bedside: Fecal calprotectin in inflammatory bowel diseases clinical setting. World J Gastroenterol 2018; 24:3681-3694. [PMID: 30197475 PMCID: PMC6127662 DOI: 10.3748/wjg.v24.i33.3681] [Citation(s) in RCA: 120] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 06/05/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Fecal calprotectin (FC) has emerged as one of the most useful tools for clinical management of inflammatory bowel diseases (IBD). Many different methods of assessment have been developed and different cut-offs have been suggested for different clinical settings. We carried out a comprehensive literature review of the most relevant FC-related topics: the role of FC in discriminating between IBD and irritable bowel syndrome (IBS) and its use in managing IBD patients In patients with intestinal symptoms, due to the high negative predictive value a normal FC level reliably rules out active IBD. In IBD patients a correlation with both mucosal healing and histology was found, and there is increasing evidence that FC assessment can be helpful in monitoring disease activity and response to therapy as well as in predicting relapse, post-operative recurrence or pouchitis. Recently, its use in the context of a treat-to-target approach led to a better outcome than clinically-based therapy adjustment in patients with early Crohn’s disease. In conclusion, FC measurement represents a cheap, safe and reliable test, easy to perform and with a good reproducibility. The main concerns are still related to the choice of the optimal cut-off, both for differentiating IBD from IBS, and for the management of IBD patients.
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Affiliation(s)
- Maria Gloria Mumolo
- Department of General Surgery and Gastroenterology, Gastroenterology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa 56124, Italy
| | - Lorenzo Bertani
- Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Linda Ceccarelli
- Department of General Surgery and Gastroenterology, Gastroenterology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa 56124, Italy
| | - Gabriella Laino
- Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Giorgia Di Fluri
- Department of General Surgery and Gastroenterology, Gastroenterology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa 56124, Italy
| | - Eleonora Albano
- Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Gherardo Tapete
- Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Francesco Costa
- Department of General Surgery and Gastroenterology, Gastroenterology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa 56124, Italy
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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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Reenaers C, Bossuyt P, Hindryckx P, Vanpoucke H, Cremer A, Baert F. Expert opinion for use of faecal calprotectin in diagnosis and monitoring of inflammatory bowel disease in daily clinical practice. United European Gastroenterol J 2018; 6:1117-1125. [PMID: 30288273 DOI: 10.1177/2050640618784046] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Accepted: 05/09/2018] [Indexed: 12/20/2022] Open
Abstract
Background Despite many publications regarding the role of faecal calprotectin (FC) in inflammatory bowel disease (IBD), clear recommendations for its use in clinical practice are currently lacking in the literature. Aim The aim of this article is to provide practical guidance for clinicians for the use of FC in the detection and management of patients with IBD. Methods All relevant publications were analysed and practical statements were proposed based on a Delphi consensus approach. Results Different commercial assays have been developed but international standardisation is lacking. FC can help in the diagnosis process of IBD. In IBD, FC can predict response to therapy, detect subclinical inflammation and help to drive treatment decisions to achieve better endoscopic and clinical outcomes. After Crohn's surgery FC can identify patients with early endoscopic recurrence. Conclusion Although major therapeutic changes should not be based on FC alone, FC is a valuable tool to optimise the care for IBD patients.
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Affiliation(s)
| | - Peter Bossuyt
- Department of Gastroenterology, Imelda General Hospital, Bonheiden, Belgium
| | - Pieter Hindryckx
- Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Hilde Vanpoucke
- Department of Laboratory Medicine, AZ Delta, Roeselare-Menen, West-Vlaanderen, Belgium
| | - Anneline Cremer
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Filip Baert
- Department of Gastroenterology, AZ Delta, Roeselare, Belgium
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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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Chen JM, Liu T, Gao S, Tong XD, Deng FH, Nie B. Efficacy of noninvasive evaluations in monitoring inflammatory bowel disease activity: A prospective study in China. World J Gastroenterol 2017; 23:8235-8247. [PMID: 29290660 PMCID: PMC5739930 DOI: 10.3748/wjg.v23.i46.8235] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Revised: 09/28/2017] [Accepted: 11/01/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To optimize the efficacy of noninvasive evaluations in monitoring the endoscopic activity of inflammatory bowel disease (IBD).
METHODS Fecal calprotectin (FC), clinical activity index (CDAI or CAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT) were measured for 136 IBD patients. Also, FC was measured in 25 irritable bowel syndrome (IBS) patients that served as controls. Then, endoscopic activity was determined by other two endoscopists for colonic or ileo-colonic Crohn’s disease (CICD) with the “simple endoscopic score for Crohn’s disease” (SES-CD), CD-related surgery patients with the Rutgeerts score, and ulcerative colitis (UC) with the Mayo score. The efficacies of these evaluations to predict the endoscopic disease activity were assessed by Mann-Whitney test, χ2 test, Spearman’s correlation, and multiple linear regression analysis.
RESULTS The median FC levels in CD, UC, and IBS patients were 449.6 (IQR, 137.9-1344.8), 497.9 (IQR, 131.7-118.0), and 9.9 (IQR, 049.7) μg/g, respectively (P < 0.001). For FC, CDAI or CAI, CRP, and ESR differed significantly between endoscopic active and remission in CICD and UC patients, but not in CD-related surgery patients. The SES-CD correlated closely with levels of FC (r = 0.802), followed by CDAI (r = 0.734), CRP (r = 0.658), and ESR (r = 0.557). The Mayo score also correlated significantly with FC (r = 0.837), CAI (r = 0.776), ESR (r = 0.644), and CRP (r = 0.634). For FC, a cut-off value of 250 μg/g indicated endoscopic active inflammation with accuracies of 87.5%, 60%, and 91.1%, respectively, for CICD, CD-related surgery, and UC patients. Moreover, clinical FC activity (CFA) calculated as 0.8 × FC + 4.6 × CDAI showed higher area under the curve (AUC) of 0.962 for CICD and CFA calculated as 0.2 × FC + 50 × CAI showed higher AUC (0.980) for UC patients than the FC. Also, the diagnostic accuracy of FC in identifying patients with mucosal inflammation in clinical remission was reflected by an AUC of 0.91 for CICD and 0.96 for UC patients.
CONCLUSION FC is the most promising noninvasive evaluation for monitoring the endoscopic activity of CICD and UC. CFA might be more accurate for IBD activity evaluation.
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Affiliation(s)
- Jin-Min Chen
- Department of Gastroenterology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Tao Liu
- Department of Gastroenterology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510665, Guangdong Province, China
| | - Shan Gao
- Department of Gastroenterology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Xu-Dong Tong
- Department of Gastroenterology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Fei-Hong Deng
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Biao Nie
- Department of Gastroenterology, the First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510630, Guangdong Province, China
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Yamamoto T, Shimoyama T. Monitoring and detection of disease recurrence after resection for Crohn's disease: the role of non-invasive fecal biomarkers. Expert Rev Gastroenterol Hepatol 2017; 11:899-909. [PMID: 28708427 DOI: 10.1080/17474124.2017.1356226] [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: 12/19/2022]
Abstract
Ileocolonoscopy is the gold standard for the diagnosis and assessment of postoperative recurrence in Crohn's disease (CD). Nevertheless, endoscopy is time-consuming and invasive. A minimally invasive and simple screening test would improve patient adherence to examination and provide greater clinical benefit. A number of fecal biomarkers have been evaluated for their utility for the diagnosis and monitoring of inflammatory bowel disease as alternative tests to endoscopy. Area covered: In this review, we focused on the utility of fecal biomarkers in the management of postoperative CD. Our major endeavor was to present an evidence-based assessment of the results of clinical trials on the available data. A literature search was conducted using the Medline. Expert commentary: Calprotectin and lactoferrin, both neutrophil-derived proteins, are the two most frequently used fecal biomarkers in clinical trials and practice. Several studies evaluated the role of these fecal biomarkers in patients with postoperative CD. These studies suggest that fecal calprotectin, and to a lesser degree lactoferrin, are useful in assessing endoscopic severity and in predicting future clinical recurrence after resection for CD. However, large scale, well-designed studies are necessary to rigorously evaluate the role of fecal biomarkers in postoperative CD.
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Affiliation(s)
- Takayuki Yamamoto
- a Inflammatory Bowel Disease Center , Yokkaichi Hazu Medical Center , Yokkaichi , Japan.,b Department of Surgery , Yokkaichi Hazu Medical Center , Yokkaichi , Japan
| | - Takahiro Shimoyama
- a Inflammatory Bowel Disease Center , Yokkaichi Hazu Medical Center , Yokkaichi , Japan.,b Department of Surgery , Yokkaichi Hazu Medical Center , Yokkaichi , Japan
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Shimoyama T, Yamamoto T, Umegae S, Matsumoto K. Faecal biomarkers for screening small bowel inflammation in patients with Crohn's disease: a prospective study. Therap Adv Gastroenterol 2017; 10:577-587. [PMID: 28835772 PMCID: PMC5557189 DOI: 10.1177/1756283x17717683] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Accepted: 05/11/2017] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND The value of faecal biomarkers for screening small bowel inflammation in patients with Crohn's disease (CD) remains to be elucidated. This prospective study was to evaluate the utility of faecal biomarkers for detecting small intestinal inflammation. METHODS A total of 122 consecutive patients with a diagnosis of CD in the small intestine were screened for eligibility. Computed tomography enterography (CTE) was undertaken to evaluate small bowel inflammation followed by colonoscopy to confirm no large bowel involvement. Seventy eligible patients with inflammation confined to the small intestine were included. Faecal samples were collected for assaying calprotectin, lactoferrin and haemoglobin. For assessing the degree of small bowel inflammation, a semi-quantitative scoring system (CTE0, normal; CTE1, mild; CTE2, moderate; CTE3, severe) was applied. RESULTS The median calprotectin, lactoferrin and haemoglobin levels were significantly higher in patients with small bowel inflammation, CTE scores 1-3 (n = 42) versus 0 (n = 28): calprotectin, 330 versus 40 ng/ml, p < 0.0001; lactoferrin, 14 versus 3 ng/ml, p < 0.0001; haemoglobin, 29.5 versus 6.5 ng/ml, p = 0.005. There was a strong positive relationship between the faecal biomarkers and CTE score: calprotectin, p < 0.0001; lactoferrin, p < 0.0001; haemoglobin, p = 0.0004. A cutoff value of 140 ng/ml for calprotectin had a sensitivity of 69% and a specificity of 82% with an area under the receiver operating characteristic curve (AUC) of 0.82 to detect small bowel inflammation (CTE scores 1-3), while lactoferrin 6 ng/ml had a sensitivity of 69% and a specificity of 79% with an AUC of 0.83, and haemoglobin 9 ng/ml showed a sensitivity of 71% and a specificity of 39% with an AUC of 0.70. CONCLUSIONS Faecal calprotectin, lactoferrin, and to a lesser degree haemoglobin are relevant biomarkers for screening small bowel inflammation in CD patients without large bowel involvement. Further well-designed large-scale studies in this clinical setting should strengthen our findings.
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Affiliation(s)
- Takahiro Shimoyama
- Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Mie, Japan
| | | | - Satoru Umegae
- Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Mie, Japan
| | - Koichi Matsumoto
- Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Mie, Japan
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Abstract
Over the last thirty years knowledge on fecal biomarkers (FM) has substantially increased. Nowadays these non-invasive inflammation markers are used in the daily management of inflammatory bowel disease (IBD). The interest in investigating FM was motivated by the need of a simple, quick, disposable and less invasive marker of disease activity, which might remove the need for endoscopy when following up with patients. Areas covered: Current literature was reviewed for articles regarding the role of FM in IBD diagnosis, activity, flare prediction, medication and surgical treatment response as well as how FM may differ in adult and paediatric IBD patient populations. Expert commentary: Although FM is relevant in IBD patient follow-up, there isn't enough data regarding FM reference values for different ages, different disease subtypes, disease localization/extension or response to therapy. Serial measurements of FM for each patient may be useful in accessing relapse in most patients. FM presented more consistent results when used as a predictive tool of relapse after ileocecal surgery in Crohn's disease. Ongoing research will clarify FM role in decision-making IBD daily practice.
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Affiliation(s)
- Paula Ministro
- a Gastroenterology Department , Tondela - Viseu Hospital Center , Viseu , Portugal
| | - Diana Martins
- a Gastroenterology Department , Tondela - Viseu Hospital Center , Viseu , Portugal
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Herranz Bachiller MT, Barrio Andres J, Fernandez Salazar L, Ruiz-Zorrilla R, Sancho Del Val L, Atienza Sanchez R. The utility of faecal calprotectin to predict post-operative recurrence in Crohńs disease. Scand J Gastroenterol 2016; 51:720-6. [PMID: 26758472 DOI: 10.3109/00365521.2015.1130164] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Endoscopic recurrence in Crohńs disease occurs in up to 80% of patients during the first year after surgery. Due to this, these patients need close monitoring. Faecal calprotectin has been proposed to be used as a non-invasive marker to monitor inflammatory activity. Up to now the use of faecal markers in endoscopic recurrence has been scarcely studied and with contradictory results. MATERIAL AND METHODS This was a cross-sectional observational study of diagnostic validity. It included all patients with Crohńs disease (CD) and ileocolic resection retrospectively who had had an ileocolonoscopy and a determination of faecal calprotectin before this colonoscopy, from 2007 to 2015. RESULTS Ninety-seven patients were included. We observed that the mean value of faecal calprotectin increased as the Rutgeerts score increased. The variable of that most statistical significance obtained in bivariate analysis was faecal calprotectin (p < 0.0001). Area under curve (AUC) of faecal calprotectin in endoscopic recurrence was 0.74 (95% CI: 0.644-0.842), and an optimal cut-off of 60 mcrgr/gr, obtained a score of 0.45 using Youden test. This indicated that calprotectin would have 88% Sensitivity and 58% Specificity in detecting any recurrence, the NPV was approximately 83,9%. None of the other variables studied had a significant correlation. CONCLUSION Faecal calprotectin predicts endoscopic recurrence in CD patients who have gone through surgery, however the cut-off point is still a problem so we cannot recommend calprotectin as a substitute of colonoscopy for CD monitoring and treatment adjustment.
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Affiliation(s)
| | - Jesus Barrio Andres
- a Department of Gastroenterology , Rio Hortega Hospital, Valladolid , Calle Dulzaina, 2 , Valladolid , Spain
| | - Luis Fernandez Salazar
- b Department of Gastroenterology, Universitary Clinic Hospital, Valladolid , Calle Ramón Y Cajal, S/N , Valladolid , Spain
| | - Rafael Ruiz-Zorrilla
- a Department of Gastroenterology , Rio Hortega Hospital, Valladolid , Calle Dulzaina, 2 , Valladolid , Spain
| | - Lorena Sancho Del Val
- a Department of Gastroenterology , Rio Hortega Hospital, Valladolid , Calle Dulzaina, 2 , Valladolid , Spain
| | - Ramon Atienza Sanchez
- a Department of Gastroenterology , Rio Hortega Hospital, Valladolid , Calle Dulzaina, 2 , Valladolid , Spain
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Yamamoto T, Shimoyama T, Kuriyama M. Letter: faecal calprotectin for the prediction of relapse in inactive inflammatory bowel disease. Aliment Pharmacol Ther 2016; 44:769-70. [PMID: 27593428 DOI: 10.1111/apt.13756] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- T Yamamoto
- Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Mie, Japan.
| | - T Shimoyama
- Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Mie, Japan
| | - M Kuriyama
- Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Mie, Japan
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42
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Yamamoto T, Shimoyama T, Umegae S, Matsumoto K. Serial monitoring of faecal calprotectin for the assessment of endoscopic recurrence in asymptomatic patients after ileocolonic resection for Crohn's disease: a long-term prospective study. Therap Adv Gastroenterol 2016; 9:664-70. [PMID: 27582878 PMCID: PMC4984325 DOI: 10.1177/1756283x16646562] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND It is recommended that ileocolonoscopy is performed within 1 year after resection for Crohn's disease (CD). Nevertheless, optimal monitoring strategies for recurrence after the ileocolonoscopy remain to be elucidated. This prospective study was to evaluate the value of serial monitoring of faecal calprotectin (FC) after ileocolonoscopy for the assessment of endoscopic recurrence in asymptomatic patients. METHODS Patients in clinical remission who had no endoscopic recurrence at ileocolonoscopy 6-12 months after ileocolonic resection were studied. FC levels were measured every 2 months up to 24 months after the ileocolonoscopy. When the FC level was elevated (⩾140 µg/g), a second ileocolonoscopy was immediately undertaken. In contrast, patients who maintained low FC levels (<140 µg/g) during the 24-month follow up underwent a second ileocolonoscopy at the end of the study. Endoscopic recurrence was defined as a Rutgeerts score ⩾i2. RESULTS A total of 30 patients were studied. In eight patients, the FC level was raised during the 24-month follow up. Six of the eight patients (75%) had endoscopic recurrence. Of 22 patients who maintained low FC levels, 20 (91%) had no endoscopic recurrence, whereas two showed endoscopic recurrence at the end of the follow up. The incidence of endoscopic recurrence was significantly higher in patients with elevation of FC levels versus those with maintained low FC levels (75% versus 9%). A cut-off value of 140 µg/g for FC had a sensitivity of 75%, a specificity of 91%, a positive predictive value of 75%, a negative predictive value of 91% and a diagnostic accuracy of 87% to detect endoscopic recurrence. CONCLUSIONS Consecutive monitoring of FC is useful for the assessment of endoscopic recurrence after the initial ileocolonoscopy. Increased FC levels indicate a need for repeat ileocolonoscopy, while sustained low FC levels predict a low risk of endoscopic recurrence. In patients maintaining low FC levels, unnecessary invasive endoscopic examinations can be avoided.
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Affiliation(s)
| | - Takahiro Shimoyama
- Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Mie, Japan
| | - Satoru Umegae
- Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Mie, Japan
| | - Koichi Matsumoto
- Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Mie, Japan
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Abstract
BACKGROUND Endoscopic recurrence after surgery for Crohn's disease (CD) is high, and it has important prognostic value. Crohn's disease will recur in the majority of patients after surgery. Fecal calprotectin (FC) and lactoferrin (FL) have attracted interest in the postoperative setting for predicting relapse. We have evaluated the accuracy of FC and FL in diagnosing endoscopic recurrence (ER) using the modified Rutgeerts score (MRS) compared with the Rutgeerts score (RS). METHODS A series of consecutive patients who underwent ileocolonic resection for Crohn's disease were evaluated. Biomarkers, clinical indexes, and fecal markers were recorded on the day of ileocolonoscopy. ER was defined as a MRS ≥ i2b or a RS ≥ i2. RESULTS Ninety-nine patients were included in this prospective cohort. The median time between surgery and colonoscopy was 87.5 months (IQR, 31-137). FC and FL levels were higher in patients with ER than in those in remission (Median FC, 196.5 μg/g [IQR, 96-634 μg/g] versus 42.1 μg/g [IQR 19-91.60 μg/g; P < 0.001]; Median FL, 23.27 μg/g [IQR 8.9-47.8 μg/g] versus 2 μg/g [IQR 0.9-7.26 μg/g; P < 0.001]). Using the MRS, 34% of patients presented with ER compared with 76% if the RS was used. The RS performed worse than the MRS with a decrease in sensitivity (74% versus 48% for FC and 85% versus 55% for FL) and in NPV (91% versus 33% for FC, and 90% versus 37% for FL). Furthermore, the accuracy of the MRS was higher than that of the RS (75% versus 55%). CONCLUSIONS Both FC and FL proved to correlate well with endoscopic findings in the evaluation of Crohn's disease after surgery. Both markers predicted recurrence with greater accuracy when the MRS was used. Fecal markers can be used to monitor disease recurrence after intestinal resection, with patients being selected to undergo further endoscopic evaluation.
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Campbell JP, Vaughn BP. Optimal delivery of follow-up care after surgery for Crohn's disease: current perspectives. Clin Exp Gastroenterol 2016; 9:237-48. [PMID: 27540307 PMCID: PMC4982489 DOI: 10.2147/ceg.s96078] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Despite improvements in medical therapies for Crohn’s disease (CD), up to 70% of patients require surgery within 10 years of diagnosis. Surgery is not curative, and almost all patients will experience endoscopic recurrence, and many will go on to clinical recurrence. Identifying patients at high-risk of endoscopic recurrence and standardizing postoperative assessments are essential in preventing clinical recurrence of CD. In this review, we discuss the assessment, monitoring, and treatment of postoperative CD patients. We address the various individual risk factors as well as composite risk factors. Medications used for primary CD treatment can be used in the postoperative setting to prevent endoscopic or clinical recurrence with varying efficacy, although the cost-effectiveness of these approaches are not fully understood. Future directions for postoperative CD management include evaluation of newer biologic agents such as anti-integrin therapy and fecal microbiota transplant for prevention of recurrence. Development of a standard preoperative risk assessment tool to clearly stratify those at high-risk of recurrence is necessary to guide empiric therapy. Lastly, the incorporation of noninvasive testing into disease monitoring will likely lead to early detection of endoscopic recurrence that will allow for tailored treatment to prevent clinical recurrence.
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Affiliation(s)
- James P Campbell
- Department of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA
| | - Byron P Vaughn
- Department of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA
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Regueiro M, Strong SA, Ferrari L, Fichera A. Postoperative Medical Management of Crohn's Disease: Prevention and Surveillance Strategies. J Gastrointest Surg 2016; 20:1415-20. [PMID: 27230995 DOI: 10.1007/s11605-016-3172-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Accepted: 05/10/2016] [Indexed: 01/31/2023]
Affiliation(s)
- Miguel Regueiro
- University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Scott A Strong
- Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Linda Ferrari
- Department of Surgery, University of Washington Medical Center, 1959 NE Pacific St, Box 356410, Seattle, WA, 98195, USA
| | - Alessandro Fichera
- Department of Surgery, University of Washington Medical Center, 1959 NE Pacific St, Box 356410, Seattle, WA, 98195, USA.
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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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Caccaro R, Angriman I, D’Incà R. Relevance of fecal calprotectin and lactoferrin in the post-operative management of inflammatory bowel diseases. World J Gastrointest Surg 2016; 8:193-201. [PMID: 27022446 PMCID: PMC4807320 DOI: 10.4240/wjgs.v8.i3.193] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Revised: 11/28/2015] [Accepted: 01/11/2016] [Indexed: 02/06/2023] Open
Abstract
The role of fecal lactoferrin and calprotectin has been extensively studied in many areas of inflammatory bowel disease (IBD) patients’ management. The post-operative setting in both Crohn’s disease (CD) and ulcerative colitis (UC) patients has been less investigated although few promising results come from small, cross-sectional studies. Therefore, the current post-operative management still requires endoscopy 6-12 mo after intestinal resection for CD in order to exclude endoscopic recurrence and plan the therapeutic strategy. In patients who underwent restorative proctocolectomy, endoscopy is required whenever symptoms includes the possibility of pouchitis. There is emerging evidence that fecal calprotectin and lactoferrin are useful surrogate markers of inflammation in the post-operative setting, they correlate with the presence and severity of endoscopic recurrence according to Rutgeerts’ score and possibly predict the subsequent clinical recurrence and response to therapy in CD patients. Similarly, fecal markers show a good correlation with the presence of pouchitis, as confirmed by endoscopy in operated UC patients. Fecal calprotectin seems to be able to predict the short-term development of pouchitis in asymptomatic patients and to vary according to response to medical treatment. The possibility of both fecal markers to used in the routine clinical practice for monitoring IBD patients in the post-operative setting should be confirmed in multicentric clinical trial with large sample set. An algorithm that can predict the optimal use and timing of fecal markers testing, the effective need and timing of endoscopy and the cost-effectiveness of these as a strategy of care would be of great interest.
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Prata MDMG, Havt A, Bolick DT, Pinkerton R, Lima A, Guerrant RL. Comparisons between myeloperoxidase, lactoferrin, calprotectin and lipocalin-2, as fecal biomarkers of intestinal inflammation in malnourished children. ACTA ACUST UNITED AC 2016; 2:134-139. [PMID: 27746954 PMCID: PMC5061054 DOI: 10.15761/jts.1000130] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Fecal biomarkers have emerged as important tools to assess intestinal inflammation and enteropathy. The aim of this study was to investigate the correlations between the fecal markers, myeloperoxidase (MPO), lactoferrin (FL), calprotectin (FC) and lipocalin-2 (Lcn-2), and to compare differences by breastfeeding status as well as normalization by fecal protein or by fecal weight. Simultaneous, quantitative MPO, FL, FC and Lcn-2, levels were determined in frozen fecal specimens collected from 78 children (mean age 15.2 ± 5.3 months) in a case-control study of childhood malnutrition in Brazil. The biomarker concentrations were measured by enzymelinked immunosorbent assay. The correlations among all biomarkers were significant (P<0.01). There were stronger correlations of fecal MPO with fecal lactoferrin and calprotectin, with lower, but still highly significant correlations of all 3 inflammatory biomarkers with Lcn-2 likely because the latter may also reflect enterocyte damage as well as neutrophil presence. Furthermore, the biomarker results with protein normalized compared to simple fecal weight normalized values showed only a slightly better correlation suggesting that the added cost and time for protein normalization added little to carefully measured fecal weights as denominators. In conclusion, fecal MPO correlates tightly with fecal lactoferrin and calprotectin irrespective of breastfeeding status and provides a common, available biomarker for comparison of human and animal model studies.
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Affiliation(s)
- Mara de Moura Gondim Prata
- Department of Physiology and Pharmacology and INCT-Biomedicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - A Havt
- Department of Physiology and Pharmacology and INCT-Biomedicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - D T Bolick
- Center for Global Health, Division of Infectious Diseases and International Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
| | - R Pinkerton
- Department of Physiology and Pharmacology and INCT-Biomedicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - Aam Lima
- Department of Physiology and Pharmacology and INCT-Biomedicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | - R L Guerrant
- Center for Global Health, Division of Infectious Diseases and International Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; Department of Physiology and Pharmacology and INCT-Biomedicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
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Abstract
There is no gold standard for the diagnosis and monitoring of inflammatory bowel diseases (IBD). Biomarkers are useful tools for the management of patients suffering from IBD. However, they should be used only when their additional information is useful for clinical decision-making. In principal, four situations during the management of an individual IBD patient can be discriminated from a clinical standpoint in which biomarkers provide useful information. First, biomarkers may be helpful when the diagnosis of IBD is established and aid in the discrimination between ulcerative colitis (UC) and Crohn's disease (CD) is necessary. Second, biomarkers may be helpful in the prognostic evaluation of IBD severity or disease behavior and for early decisions on the best treatment. The third situation in which biomarkers are useful is the evaluation of disease activity during the disease course, for monitoring and for guidance of ongoing treatment. Finally, the fourth typical situation when biomarkers are of value is after surgery to predict or diagnose a relapse of the disease. From a clinical point of view, it may be more useful to discuss specific biomarkers and their individual value and impact in these four prototypic situations than to sum up advantages and disadvantages for each biomarker isolated from the clinical situation. Therefore, this overview is structured in chapters reflecting those four typical situations during the disease course of IBD patents to critically evaluate the potential and value of each of the biomarkers in the specific situation.
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Affiliation(s)
- Gerhard Rogler
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland,
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