Prediction of disease activity of Crohn's disease through fecal calprotectin evaluated by balloon-assisted endoscopy
Fumihiko Iwamoto
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorCorresponding Author
Katsuyoshi Matsuoka
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Correspondence
Mamoru Watanabe and Katsuyoshi Matsuoka, Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Email: [email protected]; [email protected]
Search for more papers by this authorMaiko Motobayashi
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorKento Takenaka
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorToru Kuno
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorKeisuke Tanaka
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorYuya Tsukui
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorShoji Kobayashi
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorTakashi Yoshida
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorToshimitsu Fujii
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorEiko Saito
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorTatsuya Yamaguchi
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorMasakazu Nagahori
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorTadashi Sato
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorKazuo Ohtsuka
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorNobuyuki Enomoto
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorCorresponding Author
Mamoru Watanabe
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Correspondence
Mamoru Watanabe and Katsuyoshi Matsuoka, Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Email: [email protected]; [email protected]
Search for more papers by this authorFumihiko Iwamoto
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorCorresponding Author
Katsuyoshi Matsuoka
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Correspondence
Mamoru Watanabe and Katsuyoshi Matsuoka, Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Email: [email protected]; [email protected]
Search for more papers by this authorMaiko Motobayashi
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorKento Takenaka
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorToru Kuno
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorKeisuke Tanaka
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorYuya Tsukui
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorShoji Kobayashi
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorTakashi Yoshida
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorToshimitsu Fujii
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorEiko Saito
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorTatsuya Yamaguchi
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorMasakazu Nagahori
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorTadashi Sato
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorKazuo Ohtsuka
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Search for more papers by this authorNobuyuki Enomoto
First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan
Search for more papers by this authorCorresponding Author
Mamoru Watanabe
Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
Correspondence
Mamoru Watanabe and Katsuyoshi Matsuoka, Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Email: [email protected]; [email protected]
Search for more papers by this authorAbstract
Background and Aim
Fecal calprotectin (FC) is a useful marker for assessing the activity of intestinal inflammation. However, most studies have used ileocolonoscopy to evaluate the association of FC with intestinal inflammation, and it is not clear whether FC is useful for the evaluation of small-bowel Crohn's disease (CD). This study aimed to determine the usefulness of FC for predicting intestinal inflammation evaluated by balloon-assisted endoscopy (BAE), which can visualize the deep small intestine.
Methods
This was a cross-sectional, observational study involving 69 CD patients, 39 of whom had only small-bowel disease. The extended simplified endoscopic activity score for Crohn's disease (eSES-CD) was calculated based on the findings of BAE. Mucosal healing was defined as an eSES-CD of 0.
Results
In all CD patients, FC levels were correlated with the eSES-CD (r = 0.663, P < 0.001). The cutoff value to predict mucosal healing was 92 mg/kg, with a sensitivity of 94%, specificity of 88%, positive predictive value of 98%, negative predictive value of 64%, and the area under the curve of 0.91. Even in small-bowel CD patients, FC levels were correlated with the eSES-CD (r = 0.607, P < 0.001). The cutoff value was 92 mg/kg, with a sensitivity of 87%, specificity of 88%, positive predictive value of 96%, negative predictive value of 64%, and area under the curve of 0.85.
Conclusions
Fecal calprotectin showed a significant correlation with the intestinal inflammation evaluated with BAE even in patients with only small intestinal disease. FC is useful for the evaluation of CD including both the small and large intestines.
Supporting Information
| Filename | Description |
|---|---|
| jgh14310-sup-0001-Supplementary tables.docxWord 2007 document , 29.2 KB |
Table S1. Definitions of extended simplified endoscopic activity score for Crohn's disease (eSES-CD). Table S2. Correlation between each variable and FC in all patients. Table S3. Accuracy of each marker to predict mucosal healing in patients with small intestinal Crohn's disease (n = 39). Table S4. Multiple linear regression analysis by each marker in patients with small intestinal Crohn's disease (n = 39). |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Lichtenstein GR, Hanauer SB, Sandborn WJ, Practice Parameters Committee of American College of G. Management of Crohn's disease in adults. Am. J. Gastroenterol. 2009; 104: 465–483 quiz 4, 84.
- 2Baert F, Moortgat L, Van Assche G et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease. Gastroenterology 2010; 138: 463–468 quiz e10–1.
- 3Schnitzler F, Fidder H, Ferrante M et al. Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn's disease. Inflamm. Bowel Dis. 2009; 15: 1295–1301.
- 4Froslie KF, Jahnsen J, Moum BA, Vatn MH. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology 2007; 133: 412–422.
- 5Moreels TG. Small bowel enteroscopy in Crohn's disease. Ann. Gastroenterol. 2012; 25: 14–20.
- 6Upchurch BR, Sanaka MR, Lopez AR, Vargo JJ. The clinical utility of single-balloon enteroscopy: a single-center experience of 172 procedures. Gastrointest. Endosc. 2010; 71: 1218–1223.
- 7Tharian B, Caddy G, Tham TC. Enteroscopy in small bowel Crohn's disease: a review. World J. Gastrointest Endosc. 2013; 5: 476–486.
- 8Fagerhol MK. Nomenclature for proteins: is calprotectin a proper name for the elusive myelomonocytic protein? Clin. Mol. Pathol. 1996; 49: M74–M79.
- 9Roseth AG, Schmidt PN, Fagerhol MK. Correlation between faecal excretion of indium-111-labelled granulocytes and calprotectin, a granulocyte marker protein, in patients with inflammatory bowel disease. Scand. J. Gastroenterol. 1999; 34: 50–54.
- 10Roseth AG, Fagerhol MK, Aadland E, Schjonsby H. Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. Scand. J. Gastroenterol. 1992; 27: 793–798.
- 11Dolwani S, Metzner M, Wassell JJ, Yong A, Hawthorne AB. Diagnostic accuracy of faecal calprotectin estimation in prediction of abnormal small bowel radiology. Aliment. Pharmacol. Ther. 2004; 20: 615–621.
- 12Roth J, Vogl T, Sorg C, Sunderkotter C. Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules. Trends Immunol. 2003; 24: 155–158.
- 13Johne B, Fagerhol MK, Lyberg T et al. Functional and clinical aspects of the myelomonocyte protein calprotectin. Mol. Pathol.: MP. 1997; 50: 113–123.
- 14Manolakis AC, Kapsoritakis AN, Tiaka EK, Potamianos SP. Calprotectin, calgranulin C, and other members of the s100 protein family in inflammatory bowel disease. Dig. Dis. Sci. 2011; 56: 1601–1611.
- 15Tibble JA, Sigthorsson G, Bridger S, Fagerhol MK, Bjarnason I. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 2000; 119: 15–22.
- 16Kallel L, Ayadi I, Matri S et al. Fecal calprotectin is a predictive marker of relapse in Crohn's disease involving the colon: a prospective study. Eur. J. Gastroenterol. Hepatol. 2010; 22: 340–345.
- 17Vermeire S, Van Assche G, Rutgeerts P. Laboratory markers in IBD: useful, magic, or unnecessary toys? Gut 2006; 55: 426–431.
- 18Falvey JD, Hoskin T, Meijer B et al. Disease activity assessment in IBD: clinical indices and biomarkers fail to predict endoscopic remission. Inflamm. Bowel Dis. 2015; 21: 824–831.
- 19Jones J, Loftus EV Jr, Panaccione R et al. Relationships between disease activity and serum and fecal biomarkers in patients with Crohn's disease. Clin. Gastroenterol. Hepatol. 2008; 6: 1218–1224.
- 20Lin WC, Wong JM, Tung CC et al. Fecal calprotectin correlated with endoscopic remission for Asian inflammatory bowel disease patients. World J. Gastroenterol. 2015; 21: 13566–13573.
- 21Sipponen T, Savilahti E, Kolho KL, Nuutinen H, Turunen U, Farkkila M. Crohn's disease activity assessed by fecal calprotectin and lactoferrin: correlation with Crohn's disease activity index and endoscopic findings. Inflamm. Bowel Dis. 2008; 14: 40–46.
- 22D'Haens G, Ferrante M, Vermeire S et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm. Bowel Dis. 2012; 18: 2218–2224.
- 23Inokuchi T, Kato J, Hiraoka S et al. Fecal immunochemical test versus fecal calprotectin for prediction of mucosal healing in Crohn's disease. Inflamm. Bowel Dis. 2016; 22: 1078–1085.
- 24Arai T, Takeuchi K, Miyamura M et al. Level of fecal calprotectin correlates with severity of small bowel Crohn's disease, measured by balloon-assisted enteroscopy and computed tomography enterography. Clin. Gastroenterol. Hepatol. 2017; 15: 56–62.
- 25Kawashima K, Ishihara S, Yuki T et al. Fecal calprotectin more accurately predicts endoscopic remission of Crohn's disease than serological biomarkers evaluated using balloon-assisted enteroscopy. Inflamm. Bowel Dis. 2017.
- 26Harvey RF, Bradshaw JM. A simple index of Crohn's-disease activity. Lancet (London, England). 1980; 1: 514.
- 27Takenaka K, Ohtsuka K, Kitazume Y et al. Comparison of magnetic resonance and balloon enteroscopic examination of the small intestine in patients with Crohn's disease. Gastroenterology 2014; 147: 334–42.e3.
- 28Daperno M, D'Haens G, Van Assche G et al. Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest. Endosc. 2004; 60: 505–512.
- 29Boon GJ, Day AS, Mulder CJ, Gearry RB. Are faecal markers good indicators of mucosal healing in inflammatory bowel disease? World J. Gastroenterol. 2015; 21: 11469–11480.
- 30Schoepfer AM, Beglinger C, Straumann A et al. Fecal calprotectin correlates more closely with the simple endoscopic score for Crohn's disease (SES-CD) than CRP, blood leukocytes, and the CDAI. Am. J. Gastroenterol. 2010; 105: 162–169.
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