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Armas-Ingavélez MP, Galárraga-Pérez EA. Utility of fecal calprotectin in the diagnosis of inflammatory bowel diseases. SALUD, CIENCIA Y TECNOLOGÍA 2025; 5:1125. [DOI: 10.56294/saludcyt20251125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Introduction: Inflammatory bowel disease involves two main disorders: Crohn's disease and ulcerative colitis. Colonoscopy with biopsy is considered the gold standard for the diagnosis of IBD, although these are invasive and costly techniques. In recent years, fecal calprotectin has gained relevance as a non-invasive biomarker with significant clinical utility. The effectiveness of fecal calprotectin has been demonstrated in distinguishing between IBD and irritable bowel syndrome, predicting endoscopic and histological activity, as well as disease recurrence.Objective: Review the current literature on the clinical utility of fecal calprotectin in the diagnosis and management of inflammatory bowel diseases.Methods: Systematic review based on the PRISMA method, of studies obtained through searches in Scopus, PubMed, Virtual Health Library, Web of Science, Latindex, and Google Scholar. Primary and secondary studies published in the last five years in English and Spanish were included.Results: Nineteen studies were analyzed, describing high sensitivity and specificity in distinguishing IBD from IBS, helping to reduce the rate of unnecessary colonoscopies in patients with non-specific gastrointestinal symptoms. Additionally, fecal calprotectin was found to significantly correlate with endoscopic and histological activity.Conclusions: Fecal calprotectin is a reliable biomarker of mucosal inflammation, capable of identifying patients with a higher likelihood of having IBD, allowing for better management of colonoscopy resources and reducing associated costs.
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Biedermann L, Doulberis M, Schreiner P, Nielsen OH, The FO, Brand S, Burk S, Hruz P, Juillerat P, Krieger-Grübel C, Leu K, Leventhal GE, Misselwitz B, Scharl S, Schoepfer A, Seibold F, Herfarth H, Rogler G. Efficacy and Safety of Anthocyanin-Rich Extract in Patients with Ulcerative Colitis: A Randomized Controlled Trial. Nutrients 2024; 16:4197. [PMID: 39683589 PMCID: PMC11644667 DOI: 10.3390/nu16234197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 11/29/2024] [Accepted: 12/02/2024] [Indexed: 12/18/2024] Open
Abstract
Background: Bilberries are effective in inducing clinical, endoscopic, and biochemical improvement in ulcerative colitis (UC) patients. The aim of this study was to investigate the efficacy of anthocyanin-rich extract (ACRE), the bioactive ingredient of bilberries, in a controlled clinical trial in moderate-to-severe UC. Methods: A multi-center, randomized, placebo-controlled, double-blind study with a parallel group was conducted. Initially, the study was planned for 100 patients; nevertheless, it prematurely ended due to COVID-19. Patients had moderate-to-severe active UC at screening (a Mayo score of 6-12, an endoscopic sub-score ≥ 2) and were randomized at baseline. The primary endpoint was a clinical response (week 8, a total Mayo score reduction ≥ 3 points). Fecal calprotectin (FC) and a centrally read endoscopic response were among the secondary endpoints. Results: Out of 48 patients (6 Swiss centers), 34 were randomized. Eighteen ACRE and eight placebo patients could be analyzed (per protocol set). Half (9/18) of ACRE patients and 3/8 of placebo patients responded clinically (p = 0.278). An improvement in the Mayo score was observed in the ACRE arm (77.8% vs. 62.5% placebo). FC dropped from 1049 ± 1139 to 557 ± 756 μg/g for ACRE but not for the placebo group (947 ± 1039 to 1040 ± 1179; p = 0.035). Serious adverse events were rare. Conclusions: ACRE treatment did not yield significant superiority to the placebo. Furthermore, the placebo response was unusually high. Moreover, there was a significant calprotectin decrease at the end of treatment, indicative of ACRE efficacy in UC.
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Affiliation(s)
- Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (L.B.); (M.D.); (P.S.); (F.O.T.); (S.B.); (K.L.); (S.S.)
| | - Michael Doulberis
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (L.B.); (M.D.); (P.S.); (F.O.T.); (S.B.); (K.L.); (S.S.)
- Gastroklinik, Private Gastroenterological Practice, 8810 Horgen, Switzerland
- Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, 5001 Aarau, Switzerland
| | - Philipp Schreiner
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (L.B.); (M.D.); (P.S.); (F.O.T.); (S.B.); (K.L.); (S.S.)
| | - Ole Haagen Nielsen
- Department of Gastroenterology, Herlev and Gentofte Hospital, University of Copenhagen, 2730 Herlev, Denmark;
| | - Frans Olivier The
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (L.B.); (M.D.); (P.S.); (F.O.T.); (S.B.); (K.L.); (S.S.)
| | - Stephan Brand
- Department of Gastroenterology and Hepatology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland; (S.B.); (C.K.-G.)
| | - Sabine Burk
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (L.B.); (M.D.); (P.S.); (F.O.T.); (S.B.); (K.L.); (S.S.)
| | - Petr Hruz
- Department of Gastroenterology, Clarunis-University Center for Gastrointestinal and Liver Diseases, 4052 Basel, Switzerland;
| | - Pascal Juillerat
- Intesto Crohn and Colitis Center, 3012 Bern, Switzerland; (P.J.); (F.S.)
| | - Claudia Krieger-Grübel
- Department of Gastroenterology and Hepatology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland; (S.B.); (C.K.-G.)
| | - Kristin Leu
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (L.B.); (M.D.); (P.S.); (F.O.T.); (S.B.); (K.L.); (S.S.)
| | - Gabriel E. Leventhal
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (L.B.); (M.D.); (P.S.); (F.O.T.); (S.B.); (K.L.); (S.S.)
| | - Benjamin Misselwitz
- Department of Visceral Surgery and Medicine, Inselspital Bern University Hospital, University of Bern, 3010 Bern, Switzerland;
| | - Sylvie Scharl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (L.B.); (M.D.); (P.S.); (F.O.T.); (S.B.); (K.L.); (S.S.)
| | - Alain Schoepfer
- Department of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland;
| | - Frank Seibold
- Intesto Crohn and Colitis Center, 3012 Bern, Switzerland; (P.J.); (F.S.)
| | - Hans Herfarth
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA;
| | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland; (L.B.); (M.D.); (P.S.); (F.O.T.); (S.B.); (K.L.); (S.S.)
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Bahaa A, Elbaz T, Elmakhzangy H, Shehata M, Abd El-Kareem D, Gaber A, Hashem MB, El Raziky M. Assessment of IBD disease activity by Interleukin-6 and serum amyloid A in relation with fecal calprotectin and endoscopic indices. Arab J Gastroenterol 2024; 25:299-305. [PMID: 39039004 DOI: 10.1016/j.ajg.2024.07.003] [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: 03/14/2024] [Accepted: 07/05/2024] [Indexed: 07/24/2024]
Abstract
BACKGROUND AND STUDY AIMS Close monitoring of disease activity in IBD patients is essential to avoid long term complications. Although endoscopic assessment is the ideal monitoring tool, the usage of noninvasive biomarkers is more practical and patient friendly. We aimed to study the performance of Interleukin-6(IL-6) and Serum Amyloid A(SAA) as serum biomarkers in assessment of the disease activity of IBD patients in correlation to C-reactive protein (CRP), Fecal Calprotectin (FC) and endoscopic indices. METHODS 83 IBD (26 CD and 57 UC) patients on stable treatment regimen were recruited. Serum markers included CRP, CBC, IL-6, SAA were analyzed, together with FC. These markers were compared with the endoscopic and clinical disease parameters. Harvey-Bradshaw Index (HBI) and the Simple Clinical Colitis Activity Index (SCCAI) were used to assess clinical activity in CD and UC patients, respectively. Endoscopic activity was recorded using the Simple Endoscopic Score (SES) for Crohn's disease or the Mayo Endoscopic Score (MES) for ulcerative colitis. RESULTS In prediction of disease activity, IL-6, SAA and CRP demonstrated good area under receiver operating characteristics (AUC) (>0.7), with FC being the best (0.94) for endoscopically active disease (P < 0.01). Combining FC and IL-6 or SAA improved its discriminative accuracy with an AUC (∼0.96). CONCLUSIONS FC most accurately predicts endoscopic disease activity in IBD patients, in comparison to other studied serological biomarkers. The serum IL-6 and SAA are potential predictors of endoscopic disease activity, and they might be valuable for assessment of disease activity. Finally, a composite score of FC and SAA or IL-6 can increased its diagnostic accuracy.
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Affiliation(s)
- Ahmed Bahaa
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt; Integrated Clinical and Research Centre for Intestinal Disorders (ICRID), Faculty of Medicine, Cairo University, Egypt
| | - Tamer Elbaz
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt; Integrated Clinical and Research Centre for Intestinal Disorders (ICRID), Faculty of Medicine, Cairo University, Egypt
| | - Hesham Elmakhzangy
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt
| | - Mohammed Shehata
- Chemical Pathology Department, Faculty of Medicine, Cairo University, Egypt
| | | | - AbdelAziz Gaber
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt; Integrated Clinical and Research Centre for Intestinal Disorders (ICRID), Faculty of Medicine, Cairo University, Egypt
| | - Mohamed B Hashem
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt; Integrated Clinical and Research Centre for Intestinal Disorders (ICRID), Faculty of Medicine, Cairo University, Egypt
| | - Maissa El Raziky
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt
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Shen JD, Yuan B, Zhang A, Zhou XM, Chen SJ, Deng JL, Zhang X, Jiang HY, Yu Q, Wu Q. Fecal calprotectin is a novel biomarker to predict the clinical outcomes of patients with ruptured intracranial aneurysm. J Stroke Cerebrovasc Dis 2024; 33:107634. [PMID: 38342274 DOI: 10.1016/j.jstrokecerebrovasdis.2024.107634] [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: 08/28/2023] [Revised: 01/25/2024] [Accepted: 02/09/2024] [Indexed: 02/13/2024] Open
Abstract
BACKGROUND Intracranial aneurysm (IA) is a common cerebrovascular disease and the leading cause of spontaneous subarachnoid hemorrhage. Recent evidence suggests that gut microbiota is involved in the pathophysiological process of IA through the gut-brain axis. However, the role of gut inflammation in the development of IA has yet to be clarified. Our study aimed to investigate whether fecal calprotectin (FC) level, a sensitive marker of gut inflammation, is correlated with the development of IA and the prognosis of patients with ruptured IA (RIA). METHODS 182 patients were collected from January 2022 to January 2023, including 151 patients with IA and 31 healthy individuals. 151 IA patients included 109 patients with unruptured IA (UIA) and 42 patients with RIA. The FC level was measured by enzyme-linked immunosorbent assay. Other detailed information was obtained from an electronic medical record system. RESULTS Compared with healthy controls, the FC levels in patients with IA were increased (P < 0.0001). Patients with RIA had significantly higher FC levels than UIA patients (P < 0.0001). Moreover, the FC level in RIA patients with unfavorable outcomes was higher than in RIA patients with favorable outcomes. Logistic regression analysis showed that the elevated FC level was an independent risk factor for a 3-month poor prognosis in patients with RIA (OR=1.005, 95% CI = 1.000 -1.009, P = 0.044). CONCLUSION Fecal calprotectin level is significantly elevated in IA patients, especially those with RIA. FC is a novel biomarker of 3-month poor outcomes in RIA patients.
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Affiliation(s)
- Jun-Da Shen
- Department of Neurosurgery, Jinling Hospital, Nanjing Medical University, Nanjing, China
| | - Bin Yuan
- Department of Neurosurgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, China
| | - An Zhang
- Department of Neurosurgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, China
| | - Xiao-Ming Zhou
- Department of Neurosurgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, China
| | - Shu-Juan Chen
- Department of Neurosurgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, China
| | - Jin-Long Deng
- Department of Neurosurgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, China
| | - Xin Zhang
- Department of Neurosurgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, China
| | - Hai-Yang Jiang
- Department of Surgery, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China
| | - Qing Yu
- Department of Clinical Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing 210002, China.
| | - Qi Wu
- Department of Neurosurgery, Jinling Hospital, Nanjing Medical University, Nanjing, China; Department of Neurosurgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, China.
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Oka A, Kawashima K, Kishimoto K, Kotani S, Fukunaga M, Fukuba N, Mishima Y, Oshima N, Ishimura N, Awoniyi M, Ishihara S. Validation of rapid fecal calprotectin assay using particle enhanced turbidimetric immunoassay for inflammatory bowel disease. Sci Rep 2024; 14:1653. [PMID: 38238442 PMCID: PMC10796650 DOI: 10.1038/s41598-024-51580-z] [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: 04/15/2023] [Accepted: 01/07/2024] [Indexed: 01/22/2024] Open
Abstract
Fecal calprotectin (FC) is a promising biomarker for diagnosis and treatment of inflammatory bowel disease, ulcerative colitis (UC), and Crohn's disease. An enzyme immunoassay (EIA) is widely used for FC detection, though the considerable lag time, up to several days, causes clinical management delay. This study was performed to examine the new rapid kit fCAL-turbo, which is based on a particle-enhanced turbidimetric immunoassay (15 min), by comparing FC values with other EIAs (EliA, PhiCal, Bühlmann) and endoscopic scores. Using 94 samples, fCAL-turbo showed strong significant positive correlations with the other kits (Spearman's r = 0.9178-0.9886). Of 74 UC patients, 69 underwent an endoscopy and fCAL-turbo reflected endoscopic activity with a moderate correlation with Mayo endoscopic subscore (MES) (r = 0.6945, others r = 0.6682-0.7013). Receiver operating characteristic analyses based on MES 0 versus 1-3 showed a similar efficacy as compared to the other kits (cut-off and area under the curve: 89.70 µg/g and 0.8592, respectively, others 62.35-138.4 µg/g and 0.8280-0.8611, respectively). Furthermore, multiple regression analysis confirmed that fCAL-turbo results significantly contributed to prediction of MES 0 with a higher t-value as compared to the other biomarkers. fCAL-turbo showed strong correlations with the other kits and also demonstrated excellent performance for predicting endoscopic remission of UC.
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Affiliation(s)
- Akihiko Oka
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Kousaku Kawashima
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan.
- Inflammatory Bowel Disease Center, Shimane University Hospital, Izumo, Shimane, Japan.
- Department of Internal Medicine, Matsue Seikyo General Hospital, Matsue, Shimane, Japan.
| | - Kenichi Kishimoto
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Satoshi Kotani
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Mai Fukunaga
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Nobuhiko Fukuba
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Yoshiyuki Mishima
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Naoki Oshima
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Norihisa Ishimura
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
| | - Muyiwa Awoniyi
- Department of Inflammation and Immunity, Digestive Disease and Surgery Institute, Division of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA
| | - Shunji Ishihara
- Department of Internal Medicine II, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane, 693-8501, Japan
- Inflammatory Bowel Disease Center, Shimane University Hospital, Izumo, Shimane, Japan
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Clinton JW, Cross RK. Personalized Treatment for Crohn's Disease: Current Approaches and Future Directions. Clin Exp Gastroenterol 2023; 16:249-276. [PMID: 38111516 PMCID: PMC10726957 DOI: 10.2147/ceg.s360248] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 12/04/2023] [Indexed: 12/20/2023] Open
Abstract
Crohn's disease is a complex, relapsing and remitting inflammatory disorder of the gastrointestinal tract with a variable disease course. While the treatment options for Crohn's disease have dramatically increased over the past two decades, predicting individual patient response to treatment remains a challenge. As a result, patients often cycle through multiple different therapies before finding an effective treatment which can lead to disease complications, increased costs, and decreased quality of life. Recently, there has been increased emphasis on personalized medicine in Crohn's disease to identify individual patients who require early advanced therapy to prevent complications of their disease. In this review, we summarize our current approach to management of Crohn's disease by identifying risk factors for severe or disabling disease and tailoring individual treatments to patient-specific goals. Lastly, we outline our knowledge gaps in implementing personalized Crohn's disease treatment and describe the future directions in precision medicine.
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Affiliation(s)
- Joseph William Clinton
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Raymond Keith Cross
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USA
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Li J, Xu M, Qian W, Ling F, Chen Y, Li S, Cheng Y, Zhu L. Clinical value of fecal calprotectin for evaluating disease activity in patients with Crohn's disease. Front Physiol 2023; 14:1186665. [PMID: 37324392 PMCID: PMC10267473 DOI: 10.3389/fphys.2023.1186665] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 05/24/2023] [Indexed: 06/17/2023] Open
Abstract
Objective: To explore the clinical value of fecal calprotectin (FC) for evaluating disease activity in patients with Crohn's disease (CD) and its relationship with disease location. Methods: Patients with CD were enrolled retrospectively, and clinical data, including FC levels, were collected. Clinical activity was assessed using the Crohn's disease activity index (CDAI). Endoscopic activity was assessed using a simple endoscopic score for Crohn's disease (SES-CD). The partial SES-CD (pSES-CD) was scored for the size of ulcers in each segment as defined by the SES-CD and was calculated as the sum of segmental ulcer scores. Results: This study included 273 CD patients. The FC level was significantly positively correlated with the CDAI and SES-CD, with correlation coefficients of 0.666 and 0.674, respectively. The median FC levels in patients with clinical remission and mildly active and moderately-severely active disease were 41.01, 164.20, and 444.45 μg/g. These values were 26.94, 66.77, and 327.22 μg/g during endoscopic remission and mildly and moderately-severely active stages, respectively. Compared with c-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and other biomarker parameters, FC was better at predicting disease activity for CD patients. For an FC <74.52 μg/g, the area under the curve (AUC) for predicting clinical remission was 0.86, with a sensitivity of 89.47% and a specificity of 71.70%. Moreover, endoscopic remission was predicted with a sensitivity of 68.02% and a specificity of 85.53%. The AUC was 0.83, and the cutoff value was 80.84 μg/g. In patients with ileal and (ileo) colonic CD, FC was significantly correlated with the CDAI, SES-CD, and pSES-CD. The correlation coefficients were 0.711 (CDAI), 0.473 (SES-CD), and 0.369 (pSES-CD) in patients with ileal CD and 0.687, 0.745, and 0.714 in patients with (ileo) colonic CD, respectively. For patients in remission, those in the active stage, and those with large or very large ulcers, differences in FC levels were not significant between patients with ileal and (ileo) colonic CD. Conclusion: FC is a reliable predictor of disease activity in patients with CD, including those with ileal CD. FC is thus recommended for the routine follow-up of patients with CD.
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Sood A, Singh A, Mahajan R, Midha V, Bernstein CN, Rubin DT. (Re)Appraising Remission in Ulcerative Colitis. Inflamm Bowel Dis 2022:6653351. [PMID: 35917172 DOI: 10.1093/ibd/izac170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Indexed: 12/09/2022]
Abstract
As the therapeutic targets in ulcerative colitis (UC) shift from control of symptoms to mucosal healing and prevention of disease complications like disability, colectomy, and cancer, the definition of remission has evolved. The current definition of clinical remission is variable and is determined by the clinical context in which it is being used. This results in skepticism and uncertainty about the true meaning of the term "clinical remission." In this review, the authors reexamine the definition of clinical remission and propose a novel approach to define remission in UC.
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Affiliation(s)
- Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Charles N Bernstein
- IBD Clinical and Research Centre and Section of Gastroenterology, Department of Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - David T Rubin
- Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA
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Sasidharan S, Sasson AN, Shannon KM, Ananthakrishnan AN. Fecal Calprotectin Is a Predictor of Need for Rescue Therapy in Hospitalized Severe Colitis. Inflamm Bowel Dis 2022; 28:1833-1837. [PMID: 35134899 PMCID: PMC9713501 DOI: 10.1093/ibd/izac011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Up to one-third of patients hospitalized for acute severe colitis secondary to inflammatory bowel diseases (IBD) do not adequately respond to intravenous steroids. There is an unmet need to identify a useful predictor for rescue treatment in this cohort of patients. AIMS The aim of this study was to assess the predictive efficacy of fecal calprotectin in identifying the need for medical or surgical therapy in patients with acute severe colitis. METHODS We conducted a multicenter retrospective cohort study including patients with ulcerative colitis (UC) who were hospitalized for severe exacerbation of colitis. The primary outcome was the need for in-hospital medical or surgical rescue therapy. Univariate and multivariate logistic regression was performed to identify predictors of rescue therapy. RESULTS Our study included 147 patients with UC. One-third (33%) required rescue therapy, and 13% underwent colectomy. Patients requiring rescue therapy had significantly higher fecal calprotectin (mean 1748 mcg/g vs 1353 mcg/g, P = .02) compared with those who did not. A fecal calprotectin >800 mcg/g independently predicted the need for inpatient medical rescue therapy (odds ratio, 2.61; 95% CI, 1.12-6.12). An admission calprotectin >800 mcg/g independently predicted surgery within 3 months (odds ratio, 2.88; 95% CI, 1.01-8.17). CONCLUSIONS Fecal calprotectin levels may serve as a useful noninvasive predictor of medical and surgical risk in individuals with UC presenting with acute severe colitis. This approach can facilitate earlier therapeutic interventions and improve outcomes.
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Affiliation(s)
- Saranya Sasidharan
- Division of Gastroenterology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States
| | - Alexa N Sasson
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States
| | - Kevin M Shannon
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States
| | - Ashwin N Ananthakrishnan
- Address correspondence to: Ashwin N. Ananthakrishnan, MD, MPH, 165 Cambridge Street, 9th Floor, Boston, MA 02114 ()
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Park SY, Lee SP, Kim WJ. Fecal Calprotectin Is Increased in Stroke. J Clin Med 2021; 11:jcm11010159. [PMID: 35011900 PMCID: PMC8745495 DOI: 10.3390/jcm11010159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 12/23/2021] [Accepted: 12/28/2021] [Indexed: 12/14/2022] Open
Abstract
Background: While there have been major advances in unveiling the mechanisms comprising the ischemic cascade of CNS, stroke continues to be a significant burden. There is a need to extend the focus toward peripheral changes, and the brain–gut axis has recently gained much attention. Our study aimed to evaluate gut inflammation and its association with blood variables in stroke using fecal calprotectin (FC). Methods: Fecal samples were obtained from 27 stroke patients and 27 control subjects. FC was quantitatively measured using a commercial ELISA. Laboratory data on the fecal sample collection were also collected, including CBC, ESR, glucose, creatinine, total protein, albumin, transaminases, and CRP. Results: There was a significant increase in FC levels in stroke patients compared to the controls. Furthermore, FC in stroke patients was negatively correlated with the Glasgow Coma Scale. Moreover, FC in stroke patients was positively correlated with CRP and negatively correlated with lymphocyte count and albumin. Conclusions: Our findings show that increased FC is associated with consciousness and systemic response in stroke and warrants further studies to elucidate the usefulness of FC in the management of stroke.
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Affiliation(s)
- Shin Young Park
- Department of Clinical Laboratory Science, Cheju Halla University, 38 Halladaehak-ro, Jeju-si 63092, Korea;
| | - Sang Pyung Lee
- Brain-Neuro Center, Department of Neurosurgery, Cheju Halla General Hospital, 65 Doryeong-ro, Jeju-si 63127, Korea;
| | - Woo Jin Kim
- Department of Clinical Laboratory Science, Cheju Halla University, 38 Halladaehak-ro, Jeju-si 63092, Korea;
- Department of Laboratory Medicine, EONE Laboratories, 291 Harmony-ro, Yeonsu-gu, Incheon 22014, Korea
- Correspondence: ; Tel.: +82-32-210-2108
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11
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Safa A, Bagherifard A, Hadi Al-Baseesee H, Amini Kadijani A, Yahyazadeh H, Azizi M, Akbari A, Mirzaei A. Serum Calprotectin as a Blood-Based Biomarker for Monitoring Knee Osteoarthritis at Early but Not Late Stages. Cartilage 2021; 13:1566S-1571S. [PMID: 33000650 PMCID: PMC8808838 DOI: 10.1177/1947603520961161] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE The identification of early-stage osteoarthritis (OA) is crucial for the deceleration of its progression; however, no reliable biomarker is available for this purpose. The current study aimed to determine the role of serum calprotectin in the detection of early-stage knee OA. DESIGN In a case-control study, serum samples were collected from 84 patients with primary bilateral knee OA and 52 healthy controls. The radiographic grading of knee OA was performed using the Kellgren-Lawrence classification system. Serum concentrations of calprotectin were measured using an enzyme-linked immunosorbent assay. RESULTS The mean serum calprotectin level was 2908 ± 2516 ng/mL in OA patients and 901 ± 875 ng/mL in healthy control subjects (P < 0.001). Mean serum calprotectin levels were significantly higher in the lower stages of OA: 3740 ± 2728 ng/mL in OA grade I, 3100 ± 2084 ng/mL in OA grade II, 2246 ± 1418 ng/mL in OA grade III, and 2035 ± 765 ng/mL in OA grade IV (P = 0.047). Serum calprotectin levels were significantly higher in patients with a disease duration <42 months compared with those with a disease duration >42 months (P = 0.043). CONCLUSION Serum calprotectin level increases significantly in the early stages of OA and shows a reverse association with disease severity. Therefore, it could be suggested as a promising blood-based marker for early-stage knee OA.
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Affiliation(s)
- Amin Safa
- Institute of Research and Development,
Duy Tan University, Da Nang, Viet Nam,Department of Immunology, Ophthalmology
and ENT, School of Medicine, Complutense University, Madrid, Spain
| | - Abolfazl Bagherifard
- Bone and Joint Reconstruction Research
Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran,
Iran
| | | | - Azade Amini Kadijani
- Basic and Molecular Epidemiology of
Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology
and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran,
Iran
| | - Hooman Yahyazadeh
- Bone and Joint Reconstruction Research
Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran,
Iran
| | - Masoumeh Azizi
- Molecular Medicine Department,
Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Abolfazl Akbari
- Colorectal Research Center, Iran
University of Medical Sciences, Tehran, Iran
| | - Alireza Mirzaei
- Bone and Joint Reconstruction Research
Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran,
Iran,Alireza Mirzaei, Shafa Orthopedic Hospital,
Baharestan Square, Tehran, Iran.
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12
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Jo HH, Kim EY, Jung JT, Kwon JG, Kim ES, Lee HS, Lee YJ, Kim KO, Jang BI. Value of Fecal Calprotectin Measurement During the Initial Period of Therapeutic Anti-Tubercular Trial. Clin Endosc 2021; 55:256-262. [PMID: 34736314 PMCID: PMC8996000 DOI: 10.5946/ce.2021.061] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 07/11/2021] [Indexed: 11/14/2022] Open
Abstract
Background/Aims The diagnosis of intestinal tuberculosis (ITB) is often challenging. Therapeutic anti-tubercular trial (TATT) is sometimes used for the diagnosis of ITB. We aimed to evaluate the changing pattern of fecal calprotectin (FC) levels during TATT in patients with ITB.
Methods A retrospective review was performed on the data of 39 patients who underwent TATT between September 2015 and November 2018 in five university hospitals in Daegu, South Korea. The analysis was performed for 33 patients with serial FC measurement reports.
Results The mean age of the participants was 48.8 years. The final diagnosis of ITB was confirmed in 30 patients based on complete mucosal healing on follow-up colonoscopy performed after 2 months of TATT. Before starting TATT, the mean FC level of the ITB patients was 170.2 μg/g (range, 11.5-646.5). It dropped to 25.4 μg/g (range, 11.5-75.3) and then 23.3 μg/g (range, 11.5-172.2) after one and two months of TATT, respectively. The difference in mean FC before and one month after TATT was statistically significant (p<0.001), and FC levels decreased to below 100 μg/g in all patients after one month of TATT.
Conclusions All ITB patients showed FC decline after only 1 month of TATT, and this finding correlated with complete mucosal healing in the follow-up colonoscopy after 2 months of TATT.
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Affiliation(s)
- Hyeong Ho Jo
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Eun Young Kim
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Jin Tae Jung
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Joong Goo Kwon
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Eun Soo Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Hyun Seok Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Yoo Jin Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Kyeong Ok Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Byung Ik Jang
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
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13
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Crawford E, Gestrich C, Malay S, Young D, Perry S, Splawski J, Sferra TJ, Saab S, Moses J. Association of Fecal Calprotectin With Endoscopic and Histologic Activity in Pediatric Inflammatory Bowel Disease. JPGN REPORTS 2021; 2:e129. [PMID: 37206450 PMCID: PMC10191562 DOI: 10.1097/pg9.0000000000000129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 08/16/2021] [Indexed: 05/21/2023]
Abstract
Fecal calprotectin (FC) is a noninvasive marker of intestinal inflammation used for screening and ongoing monitoring of inflammatory bowel disease (IBD); it is unclear the association of specific FC values with disease activity. The aim of our study was to examine the association of FC values with endoscopic and histologic severity. Methods We performed a retrospective chart review of patients who had FC done between 30 days and 1 day before colonoscopy at our institution. IBD patients were graded using the simple endoscopic score for Crohn's disease or Mayo endoscopic score for ulcerative colitis. Histologic slides were graded using the Geboes method. Results Three-hundred thirty-one patients were included in the study and 107 had IBD. For endoscopy, median FC was lowest for all IBD patients with no disease (181 μg/g) and highest in severe disease (921 μg/g), with significant difference between no disease and moderate and severe disease (P = 0.019, 0.003), and between mild and severe disease (P = 0.012). For histology, median FC was lowest with no disease (328 μg/g) and highest in severe disease (895 μg/g), with significant difference between no disease and moderate and severe disease (P = 0.021, 0.018). The control population had a significantly lower median FC than the IBD population in endoscopic remission (35.5 versus 181 μg/g; P = 0.018). Conclusions There was a linear increase in FC values associated with increasing disease severity in the undifferentiated IBD cohort. Values for IBD patients in endoscopic remission were significantly different from our control population. FC may be a useful noninvasive marker to assess disease severity.
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Affiliation(s)
- Erin Crawford
- From the Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UH/Rainbow Babies and Children’s Hospital, Cleveland OH
| | | | - Sindhoosha Malay
- Department of Biostatistics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland OH
| | - Denise Young
- From the Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UH/Rainbow Babies and Children’s Hospital, Cleveland OH
| | - Sharon Perry
- From the Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UH/Rainbow Babies and Children’s Hospital, Cleveland OH
| | - Judy Splawski
- From the Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UH/Rainbow Babies and Children’s Hospital, Cleveland OH
| | - Thomas J. Sferra
- From the Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UH/Rainbow Babies and Children’s Hospital, Cleveland OH
| | - Shahrazad Saab
- Department of Pathology, UH Cleveland Medical Center, Cleveland, OH
| | - Jonathan Moses
- From the Division of Pediatric Gastroenterology, Hepatology, and Nutrition, UH/Rainbow Babies and Children’s Hospital, Cleveland OH
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14
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Xiang BJ, Jiang M, Sun MJ, Dai C. Optimal Range of Fecal Calprotectin for Predicting Mucosal Healing in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Visc Med 2021; 37:338-348. [PMID: 34722717 PMCID: PMC8543348 DOI: 10.1159/000514196] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Accepted: 01/04/2021] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE Fecal calprotectin (FC) is a promising marker for assessment of inflammatory bowel disease (IBD) activity. However, the utility of FC for predicting mucosal healing (MH) of IBD patients has yet to be clearly demonstrated. The objective of our study was to perform a meta-analysis evaluating the diagnostic accuracy of FC in predicting MH of IBD patients. METHODS We systematically searched the databases for studies from inception to April 2020 that evaluated MH in IBD. 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 Sixteen studies comprising 1,682 ulcerative colitis (UC) patients and 4 studies comprising 221 Crohn's disease (CD) patients were included. The best performance of FC for predicting MH in UC was at cut-off range of 60-75 μg/g with area under the curve (AUC) of 0.88 and pooled sensitivity and specificity of 0.87 and 0.79, respectively. The pooled sensitivity and specificity values of cutoff range 180-250 μg/g for predicting MH in CD were 0.67 and 0.76, respectively. The AUC of 0.79 also revealed improved discrimination for identifying MH in CD with FC concentration. CONCLUSION Our meta-analysis has found that FC is a simple, reliable noninvasive marker for predicting MH in IBD patients. FC cutoff range 60-75 μg/g appears to have the best overall accuracy in UC patients.
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Affiliation(s)
- Bing-Jie Xiang
- Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang, China
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15
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Assessing adherence to objective disease monitoring and outcomes with adalimumab in a real-world IBD cohort. Dig Liver Dis 2021; 53:980-986. [PMID: 33640302 DOI: 10.1016/j.dld.2021.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 02/01/2021] [Accepted: 02/02/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Data suggests that tight objective monitoring may improve clinical outcomes in IBD. AIM To assess the adherence to serial tight objective monitoring(clinical and biomarkers) and its effect on clinical outcomes. METHODS We retrospectively reviewed the chart of 428 consecutive IBD patients started on adalimumab between January 1,2015-January 1,2019 [338 Crohn's disease(CD), 90 ulcerative colitis(UC)]. Clinical symptoms(assessed by Harvey-Bradshaw-Index,partial Mayo),C-Reactive Protein(CRP), and fecal calprotectin(FCAL) assessments were captured at treatment initiation and at 3,6,9, and12 months. Dose optimization and drug sustainability curves were plotted by Kaplan-Meier method. RESULTS Clinical evaluation was available in nearly all patients at 3(CD-UC:95-94%), 6(90-83%), 9(86-85%) and 12(96-89%) months. CRP testing frequency decreased in CD patients over time. Compliance to serial FCAL testing was low. Clinical remission at one-year was higher in patients adherent to early assessment visit at 3 months(p = 0.001 for CD and UC). Adherence to early follow-up resulted in earlier dose optimization in CD and UC patients(pLogrank=0.026 for UC & p = 0.09 for CD). Overall drug sustainability did not differ. CONCLUSION Clinical & CRP, but not FCAL, were frequently assessed in patients starting adalimumab. Adherence to early objective combined follow-up visits resulted in earlier dose optimization, improved one-year clinical outcomes but did not change drug sustainability.
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16
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Bromke MA, Neubauer K, Kempiński R, Krzystek-Korpacka M. Faecal Calprotectin in Assessment of Mucosal Healing in Adults with Inflammatory Bowel Disease: A Meta-Analysis. J Clin Med 2021; 10:jcm10102203. [PMID: 34069684 PMCID: PMC8161009 DOI: 10.3390/jcm10102203] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 05/12/2021] [Accepted: 05/15/2021] [Indexed: 12/12/2022] Open
Abstract
Achieving mucosal healing in patients with inflammatory bowel disease is related to a higher incidence of sustained clinical remission and it translates to lower rates of hospitalisation and surgery. The assessment methods of disease activity and response to therapy are limited and mainly rely on colonoscopy. This meta-analysis reviews the effectiveness of using faecal calprotectin as a marker for mucosal healing in inflammatory bowel disease. Two meta-analyses were conducted in parallel. The analysis on the use of faecal calprotectin in monitoring mucosal healing in colonic Crohn’s disease is based on 16 publications (17 studies). The data set for diagnostic values of faecal calprotectin in ulcerative colitis is composed of 35 original publications (total 49 studies). The DOR for the use of faecal calprotectin in Crohn’s disease is estimated to be 11.20 and the area under the sROCis 0.829. In cases of ulcerative colitis, the DOR is 14.48, while the AUC sROC is 0.858. Heterogeneity of the studies was moderatetosubstantial. Collected data show overall good sensitivity and specificity of the faecal calprotectin test, as well as a good DOR. Thus, monitoring of mucosal healing with a non-invasive faecal calprotectin test may represent an attractive option for physicians and patients with inflammatory bowel disease.
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Affiliation(s)
- Mariusz A. Bromke
- Department of Biochemistry and Immunochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland;
- Correspondence:
| | - Katarzyna Neubauer
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (K.N.); (R.K.)
| | - Radosław Kempiński
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (K.N.); (R.K.)
| | - Małgorzata Krzystek-Korpacka
- Department of Biochemistry and Immunochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland;
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17
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State M, Negreanu L, Voiosu T, Voiosu A, Balanescu P, Mateescu RB. Surrogate markers of mucosal healing in inflammatory bowel disease: A systematic review. World J Gastroenterol 2021; 27:1828-1840. [PMID: 33967560 PMCID: PMC8072191 DOI: 10.3748/wjg.v27.i16.1828] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/02/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Mucosal healing (MH) has emerged as a key therapeutic target in inflammatory bowel disease (IBD), and achievement of this goal is documented by endoscopy with biopsy. However, colonoscopy is burdensome and invasive, and substitution with an accurate noninvasive biomarker is desirable.
AIM To summarize published data regarding the performance of noninvasive biomarkers in assessing MH in IBD patients.
METHODS We conducted a systematic review of studies that reported the performance of biomarkers in diagnosing MH in patients with IBD. The main outcome measure was to review the diagnostic accuracy of serum and fecal markers that showed promising utility in assessing MH.
RESULTS We screened 1301 articles, retrieved 46 manuscripts and included 23 articles for full-text analysis. The majority of the included manuscripts referred to fecal markers (12/23), followed by circulatory markers (8/23); only 3/23 of the included manuscripts investigated combined markers (serum and/or fecal markers). Fecal calprotectin (FC) was the most investigated fecal marker for assessing MH. In ulcerative colitis, for cutoff levels ranging between 58 mcg/g and 490 mcg/g, the sensitivity was 89.7%-100% and the specificity was 62%-93.3%. For Crohn’s disease, the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g (sensitivity 50%-95.9% and specificity 52.3%-100%). The best performance for a serum marker was observed for the endoscopic healing index, which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein.
CONCLUSION Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization.
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Affiliation(s)
- Monica State
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest 020125, Romania
| | - Lucian Negreanu
- Department of Gastroenterology, Emergency University Hospital, Bucharest 050098, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
| | - Theodor Voiosu
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest 020125, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
| | - Andrei Voiosu
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest 020125, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
| | - Paul Balanescu
- Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
- Department of Internal Medicine and Research Methodology, Colentina Clinical Hospital, Bucharest 020125, Romania
| | - Radu Bogdan Mateescu
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest 020125, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
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18
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Rodrigues BL, Mazzaro MC, Nagasako CK, Ayrizono MDLS, Fagundes JJ, Leal RF. Assessment of disease activity in inflammatory bowel diseases: Non-invasive biomarkers and endoscopic scores. World J Gastrointest Endosc 2020; 12:504-520. [PMID: 33362904 PMCID: PMC7739141 DOI: 10.4253/wjge.v12.i12.504] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 10/06/2020] [Accepted: 11/05/2020] [Indexed: 02/05/2023] Open
Abstract
Inflammatory bowel diseases (IBD) comprise two major forms: Crohn's disease and ulcerative colitis. The diagnosis of IBD is based on clinical symptoms combined with results found in endoscopic and radiological examinations. In addition, the discovery of biomarkers has significantly improved the diagnosis and management of IBD. Several potential genetic, serological, fecal, microbial, histological and immunological biomarkers have been proposed for IBD, and they have been evaluated for clinical routine and clinical trials. Ileocolonoscopy, especially with biopsy collection, has been considered the standard method to diagnose IBD and to assess clinical activity of the disease, but it is limited to the colon and terminal ileum and is considered invasive. For this reason, non-invasive biomarkers are necessary for this type of chronic inflammatory disease, which affects mostly young individuals, as they are expected to have a long follow-up.
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Affiliation(s)
- Bruno Lima Rodrigues
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Márcia Carolina Mazzaro
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Cristiane Kibune Nagasako
- Department of Gastroenterology, Gastrocenter, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Maria de Lourdes Setsuko Ayrizono
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - João José Fagundes
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
| | - Raquel Franco Leal
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-878, São Paulo, Brazil
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Park SY. Age-Related Fecal Calprotectin Concentrations in Healthy Adults. KOREAN JOURNAL OF CLINICAL LABORATORY SCIENCE 2020. [DOI: 10.15324/kjcls.2020.52.3.181] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Shin Young Park
- Department of Clinical Laboratory Science, Cheju Halla University, Jeju, Korea
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20
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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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21
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Krzystek-Korpacka M, Kempiński R, Bromke M, Neubauer K. Biochemical Biomarkers of Mucosal Healing for Inflammatory Bowel Disease in Adults. Diagnostics (Basel) 2020; 10:E367. [PMID: 32498475 PMCID: PMC7344443 DOI: 10.3390/diagnostics10060367] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 05/29/2020] [Accepted: 05/30/2020] [Indexed: 02/06/2023] Open
Abstract
Mucosal healing (MH) is the key therapeutic target of inflammatory bowel disease (IBD). The evaluation of MH remains challenging, with endoscopy being the golden standard. We performed a comprehensive overview of the performance of fecal-, serum-, and urine-based biochemical markers in colonic IBD to find out whether we are ready to replace endoscopy with a non-invasive but equally accurate instrument. A Pubmed, Web of Knowledge, and Scopus search of original articles as potential MH markers in adults, published between January 2009 and March 2020, was conducted. Finally, 84 eligible studies were identified. The most frequently studied fecal marker was calprotectin (44 studies), with areas under the curves (AUCs) ranging from 0.70 to 0.99 in ulcerative colitis (UC) and from 0.70 to 0.94 in Crohn`s disease (CD), followed by lactoferrin (4 studies), matrix metalloproteinase-9 (3 studies), and lipocalin-2 (3 studies). The most frequently studied serum marker was C-reactive protein (30 studies), with AUCs ranging from 0.60 to 0.96 in UC and from 0.64 to 0.93 in CD. Fecal calprotectin is an accurate MH marker in IBD in adults; however, it cannot replace endoscopy and the application of calprotectin is hampered by the lack of standardization concerning the cut-off value. Other markers are either not sufficiently accurate or have not been studied extensively enough.
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Affiliation(s)
| | - Radosław Kempiński
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland;
| | - Mariusz Bromke
- Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland;
| | - Katarzyna Neubauer
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland;
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22
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Zhang F, Ma C, Zhang B, Bi L. Dynamic changes in gut microbiota under the influence of smoking and TNF-α-blocker in patients with ankylosing spondylitis. Clin Rheumatol 2020; 39:2653-2661. [PMID: 32219620 DOI: 10.1007/s10067-020-05032-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 01/21/2020] [Accepted: 03/05/2020] [Indexed: 12/16/2022]
Abstract
OBJECTIVES This study aimed to investigate the relationship among smoking, TNF-α-blocker therapy, and the dynamic changes in gut microbiota in patients with ankylosing spondylitis (AS). METHODS Using a 16S rRNA sequence, 98 fecal samples of 20 AS patients collected after 0, 1, 3 and 6 months of anti-TNF-α treatment and from 20 matched health controls were examined. The variation in composition, abundance, and diversity of gut microbiota was analyzed. The dynamic effects of smoking and treatment on gut microbiota and therapeutic efficacy in AS patients were studied. RESULTS The increased relative abundance of microbiota in AS nonsmokers was g_Comamonas and g_Desulfovibrio, while that in AS smokers was g_Actinomyces, g_Collinsella, g_Lachnospiraceae_UCG-008, and g_Paraprevotella. The relative abundance of gut microbiota showed dynamic variation. The improvement rate of ASDAS in AS nonsmokers was higher than that in AS smokers (2.297 vs 1.736) after anti-TNF-α treatment. The β-diversity of gut microbiota in AS smokers was lower than that in AS nonsmokers and improved with treatment. CONCLUSIONS Both smoking and TNF-α-blocker had significant effects on the composition, relative abundance, and diversity of gut microbiota in AS patients. The AS smokers characteristically shared g_Collinsella and g_Dorea. The relative abundance of gut microbiota revealed high variability and was in dynamic fluctuation during treatment. The response of gut microbiota to anti-TNF-α treatment was found to be heterogeneous and selective. AS nonsmokers showed a greater improvement rate of ASDAS-CRP with treatment than AS smokers did. The AS smokers showed a lower β-diversity of gut microbiota, and improved after treatment. Key Points • Characterized the dynamic variation in gut microbiota in AS patients classified as smokers and nonsmokers during treatment with anti-TNF-α. • Confirmed the interaction between smoking, anti-TNF-α therapy, and gut microbiota.
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Affiliation(s)
- Fangze Zhang
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, 130033, Jilin, People's Republic of China
| | - Cuili Ma
- Department of Rheumatology and Immunology, China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, 130033, Jilin, People's Republic of China
| | - Bin Zhang
- Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, 130033, Jilin, People's Republic of China.
| | - Liqi Bi
- Department of Rheumatology and Immunology, China-Japan Union Hospital of Jilin University, No.126 Xiantai Street, Changchun, 130033, Jilin, People's Republic of China.
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Cha JM. Fecal calprotectin in daily practice for patients with inflammatory bowel disease: where do we stand in Korea? Korean J Intern Med 2019; 34:60-62. [PMID: 30612419 PMCID: PMC6325448 DOI: 10.3904/kjim.2018.401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 11/18/2018] [Indexed: 11/27/2022] Open
Affiliation(s)
- Jae Myung Cha
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
- Correspondence to Jae Myung Cha, M.D. Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, 892 Dongnam-ro, Gangdong-gu, Seoul 05278, Korea Tel: +82-2-440-6113 Fax: +82-2-440-7849 E-mail:
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24
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Garcia-Montoya L, Gul H, Emery P. Recent advances in ankylosing spondylitis: understanding the disease and management. F1000Res 2018; 7. [PMID: 30345001 PMCID: PMC6173104 DOI: 10.12688/f1000research.14956.1] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/11/2018] [Indexed: 12/14/2022] Open
Abstract
The term spondyloarthritis refers to a group of immune-mediated diseases characterised by inflammation of the axial skeleton, peripheral joints, and entheses. Ankylosing spondylitis (AS) is the most common and characteristic of these entities and even though it was first described over two centuries ago, the understanding of the underlying disease mechanism remains incomplete. It is known that around 40% of patients with AS have subclinical bowel inflammation, suggesting that the origin of the disease could be in the gut. Also, more genes and new molecules have demonstrated a role in the pathogenesis of AS. In this review, we analyse the latest therapies for spondyloarthritis and the most relevant discoveries over the last three years, together with their implications for different aspects of the disease.
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Affiliation(s)
- Leticia Garcia-Montoya
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK.,NIHR Leeds Musculoskeletal Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Hanna Gul
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK.,NIHR Leeds Musculoskeletal Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Paul Emery
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK.,NIHR Leeds Musculoskeletal Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK
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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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