Systematic Review with Meta-Analysis: Fecal Calprotectin as a Surrogate Marker for Predicting Relapse in Adults with Ulcerative Colitis

Jiajia Li, Xiaojing Zhao, Xueting Li, Meijiao Lu, Hongjie Zhang, Jiajia Li, Xiaojing Zhao, Xueting Li, Meijiao Lu, Hongjie Zhang

Abstract

The clinical course of ulcerative colitis (UC) is featured by remission and relapse, which remains unpredictable. Recent studies revealed that fecal calprotectin (FC) could predict clinical relapse for UC patients in remission, which has not yet been well accepted. To detect the predictive value of FC for clinical relapse in adult UC patients based on updated literature, we carried out a comprehensive electronic search of PubMed, Web of Science, Embase, and the Cochrane Library to identify all eligible studies. Diagnostic accuracy including pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and pooled area under the receiver operating characteristic (AUROC) was calculated using a random effects model. Heterogeneity across studies was assessed by the I 2 metric. Sources of heterogeneity were detected using subgroup analysis. Metaregression was used to test potential factors correlated to DOR. Publication bias was assessed using Deek's funnel plots. In our study, 14 articles enrolling a total of 1110 participants were finally included, and all articles underwent a quality assessment. Pooled sensitivity, specificity, PLR, and NLR with 95% confidence intervals (CIs) were 0.75 (95% CI: 0.70-0.79), 0.77 (95% CI: 0.74-0.80), 3.45 (95% CI: 2.31-5.14), and 0.37 (95% CI: 0.28-0.49) respectively. The area under the summary receiver operating characteristic (sROC) curve was 0.82, and the diagnostic odds ratio was 10.54 (95% CI: 6.16-18.02). Our study suggested that FC is useful in predicting clinical relapse for adult UC patients in remission as a simple and noninvasive marker.

Figures

Figure 1
Figure 1
Study flow diagram showing the process of selecting studies concerning the diagnostic accuracy of FC in predicting relapse among adult UC patients.
Figure 2
Figure 2
QUADAS-2 risk of bias assessment. +, high; −, low; ?, unclear.
Figure 3
Figure 3
Forest plots of pooled sensitivity of FC in predicting relapse of UC in one-year follow-up (a). Forest plots of pooled specificity of FC in predicting relapse of UC (b).
Figure 4
Figure 4
Symmetrical summary receiver operator curve (sROC) for all 14 studies. The size of the circle represents the sample size of each study included in the meta-analysis.
Figure 5
Figure 5
Deeks' funnel plot.

References

    1. Burisch J., Martinato T. J. M., Lakatos P. L., ECCO -EpiCom The burden of inflammatory bowel disease in Europe. Journal of Crohn's and Colitis. 2013;7(4):322–337. doi: 10.1016/j.crohns.2013.01.010.
    1. Kappelman M. D., Rifas–Shiman S. L., Kleinman K., et al. The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clinical Gastroenterology and Hepatology. 2007;5(12):1424–1429. doi: 10.1016/j.cgh.2007.07.012.
    1. Ananthakrishnan A. N. Environmental risk factors for inflammatory bowel diseases: a review. Digestive Diseases and Sciences. 2015;60(2):290–298. doi: 10.1007/s10620-014-3350-9.
    1. Frank D. N., St. Amand A. L., Feldman R. A., Boedeker E. C., Harpaz N., Pac N. R. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(34):13780–13785. doi: 10.1073/pnas.0706625104.
    1. Cosnes J., Gower–Rousseau C., Seksik P., Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011;140(6):1785–1794.e4. doi: 10.1053/j.gastro.2011.01.055.
    1. Bunn S. K., Bisset W. M., Main M. J. C., Gray E. S., Olson S., Golden B. E. Fecal calprotectin: validation as a noninvasive measure of bowel inflammation in childhood inflammatory bowel disease. Journal of Pediatric Gastroenterology and Nutrition. 2001;33(1):14–22. doi: 10.1097/00005176-200107000-00003.
    1. Kappelman M. D., Rifas–Shiman S. L., Porter C. Q., et al. Direct health care costs of Crohn’s disease and ulcerative colitis in US children and adults. Gastroenterology. 2008;135(6):1907–1913. doi: 10.1053/j.gastro.2008.09.012.
    1. Annese V., Daperno M., Rutter M. D., et al. European evidence based consensus for endoscopy in inflammatory bowel disease. Journal of Crohns and Colitis. 2013;7(12):982–1018. doi: 10.1016/j.crohns.2013.09.016.
    1. Van Assche G., Dignass A., Bokemeyer B., et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 3: special situations. Journal of Crohn's and Colitis. 2013;7(1):1–33. doi: 10.1016/j.crohns.2012.09.005.
    1. Schoepfer A. M., Beglinger C., Straumann A., et al. Fecal calprotectin more accurately reflects endoscopic activity of ulcerative colitis than the Lichtiger Index, C-reactive protein, platelets, hemoglobin, and blood leukocytes. Inflammatory Bowel Diseases. 2013;19(2):332–341. doi: 10.1097/MIB.0b013e3182810066.
    1. Krzesiek E., Iwańczak B. Assessment of fecal calprotectin concentration as inflammatory marker in inflammatory bowel diseases in children—preliminary report. Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego. 2010;29(172):241–246.
    1. Langhorst J., Elsenbruch S., Koelzer J., Rueffer A., Michalsen A., Dobos G. J. Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN-elastase, CRP, and clinical indices. The American Journal of Gastroenterology. 2008;103(1):162–169. doi: 10.1111/j.1572-0241.2007.01556.x.
    1. van Rheenen P. F., Van de Vijver E., Fidler V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ. 2010;341(jul15 1):p. c3369. doi: 10.1136/bmj.c3369.
    1. Moher D., Liberati A., Tetzlaff J., Altman D. G., for the PRISMA Group Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339(jul21 1):p. b2535. doi: 10.1136/bmj.b2535.
    1. Whiting P. F., Weswood M. E., Rutjes A. W. S., Reitsma J. B., Bossuyt P. N. M., Kleijnen J. Evaluation of QUADAS, a tool for the quality assessment of diagnostic accuracy studies. BMC Medical Research Methodology. 2006;6(1) doi: 10.1186/1471-2288-6-9.
    1. Moses L. E., Shapiro D., Littenberg B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Statistics in Medicine. 1993;12(14):1293–1316. doi: 10.1002/sim.4780121403.
    1. Higgins J. P., Thompson S. G., Deeks J. J., Altman D. G. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–560. doi: 10.1136/bmj.327.7414.557.
    1. Mantel N., Haenszel W. Statistical Aspects of the Analysis of Data From Retrospective Studies of Disease. JNCI: Journal of the National Cancer Institute. 1959;22(4):719–748. doi: 10.1093/jnci/22.4.719.
    1. Deeks J. J., Macaskill P., Irwig L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. Journal of Clinical Epidemiology. 2005;58(9):882–893. doi: 10.1016/j.jclinepi.2005.01.016.
    1. Nakarai A., Hiraoka S., Takahashi S., et al. Simultaneous measurements of faecal calprotectin and the faecal immunochemical test in quiescent ulcerative colitis patients can stratify risk of relapse. Journal of Crohn’s and colitis. 2018;12(1):71–76. doi: 10.1093/ecco-jcc/jjx118.
    1. Yamamoto T., Shimoyama T., Umegae S., Matsumoto K. Endoscopic score vs. fecal biomarkers for predicting relapse in patients with ulcerative colitis after clinical remission and mucosal healing. Clinical and Translational Gastroenterology. 2018;9(3):p. 136. doi: 10.1038/s41424-018-0006-7.
    1. Keshteli A. H., van den Brand F. F., Madsen K. L., et al. Dietary and metabolomic determinants of relapse in ulcerative colitis patients: a pilot prospective cohort study. World Journal of Gastroenterology. 2017;23(21):3890–3899. doi: 10.3748/wjg.v23.i21.3890.
    1. Ferreiro-Iglesias R., Barreiro-de Acosta M., Otero Santiago M., et al. Fecal calprotectin as predictor of relapse in patients with inflammatory bowel disease under maintenance infliximab therapy. Journal of Clinical Gastroenterology. 2016;50(2):147–151. doi: 10.1097/MCG.0000000000000312.
    1. Theede K., Holck S., Ibsen P., Kallemose T., Nordgaard-Lassen I., Nielsen A. M. Fecal calprotectin predicts relapse and histological mucosal healing in ulcerative colitis. Inflammatory Bowel Diseases. 2016;22(5):1042–1048. doi: 10.1097/MIB.0000000000000736.
    1. Hosseini S. V., Jafari P., Taghavi S. A., et al. Fecal calprotectin is an accurate tool and correlated to Seo index in prediction of relapse in Iranian patients with ulcerative colitis. Iranian Red Crescent Medical Journal. 2015;17(2) doi: 10.5812/ircmj.22796.
    1. Scaioli E., Scagliarini M., Cardamone C., et al. Clinical application of faecal calprotectin in ulcerative colitis patients. European Journal of Gastroenterology & Hepatology. 2015;27(12):1418–1424. doi: 10.1097/MEG.0000000000000461.
    1. Yamamoto T., Shimoyama T., Matsumoto K. Consecutive monitoring of faecal calprotectin during mesalazine suppository therapy for active rectal inflammation in ulcerative colitis. Alimentary Pharmacology and Therapeutics. 2015;42(5):549–558. doi: 10.1111/apt.13308.
    1. Jauregui-Amezaga A., López-Cerón M., Aceituno M., et al. Accuracy of advanced endoscopy and fecal calprotectin for prediction of relapse in ulcerative colitis: a prospective study. Inflammatory Bowel Diseases. 2014;20(7):1187–1193. doi: 10.1097/MIB.0000000000000069.
    1. Yamamoto T., Shiraki M., Bamba T., Umegae S., Matsumoto K. Fecal calprotectin and lactoferrin as predictors of relapse in patients with quiescent ulcerative colitis during maintenance therapy. International Journal of Colorectal Disease. 2014;29(4):485–491. doi: 10.1007/s00384-013-1817-3.
    1. De Vos M., Louis E. J., Jahnsen J., et al. Consecutive Fecal Calprotectin Measurements to Predict Relapse in Patients with Ulcerative Colitis Receiving Infliximab Maintenance Therapy. Inflammatory Bowel Diseases. 2013;19(10):2111–2117. doi: 10.1097/MIB.0b013e31829b2a37.
    1. Costa F., Mumolo M. G., Ceccarelli L., et al. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn’s disease. Gut. 2005;54(3):364–368. doi: 10.1136/gut.2004.043406.
    1. Gisbert J. P., Bermejo F., Pérez-Calle J. L., et al. Fecal calprotectin and lactoferrin for the prediction of inflammatory bowel disease relapse. Inflammatory Bowel Diseases. 2009;15(8):1190–1198. doi: 10.1002/ibd.20933.
    1. García-Sánchez V., Iglesias-Flores E., González R., et al. Does fecal calprotectin predict relapse in patients with Crohn’s disease and ulcerative colitis? Journal of Crohn’s and colitis. 2010;4(2):144–152. doi: 10.1016/j.crohns.2009.09.008.
    1. Solberg I. C., Lygren I., Jahnsen J., et al. Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study) Scandinavian Journal of Gastroenterology. 2009;44(4):431–440. doi: 10.1080/00365520802600961.
    1. Casati J., Toner B. B., de Rooy E. C., Drossman D. A., Maunder R. G. Concerns of patients with inflammatory bowel disease—a review of emerging themes. Digestive Diseases and Sciences. 2000;45(1):26–31. doi: 10.1023/A:1005492806777.
    1. Lehmann F. S., Burri E., Beglinger C. The role and utility of faecal markers in inflammatory bowel disease. Therapeutic Advances in Gastroenterology. 2014;8(1):23–36. doi: 10.1177/1756283X14553384.
    1. Mao R., Xiao Y. L., Gao X., et al. Fecal calprotectin in predicting relapse of inflammatory bowel diseases: a meta-analysis of prospective studies. Inflammatory Bowel Diseases. 2012;18(10):1894–1899. doi: 10.1002/ibd.22861.
    1. Bitton A., Peppercorn M. A., Antonioli D. A., et al. Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis. Gastroenterology. 2001;120(1):13–20. doi: 10.1053/gast.2001.20912.
    1. Diamanti A., Colistro F., Basso M. S., et al. Clinical role of calprotectin assay in determining histological relapses in children affected by inflammatory bowel diseases. Inflammatory Bowel Diseases. 2008;14(9):1229–1235. doi: 10.1002/ibd.20472.
    1. Zhulina Y., Cao Y., Amcoff K., Carlson M., Tysk C., Halfvarson J. P430. Prognostic significance of serial faecal calprotectin in inflammatory bowel disease. Journal of Crohn’s and Colitis. 2016;10:S315–S318.
    1. Benchimol E. I., Fortinsky K. J., Gozdyra P., Van den Heuvel M., Van Limbergen J., Griffiths A. M. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflammatory Bowel Diseases. 2011;17(1):423–439. doi: 10.1002/ibd.21349.
    1. Krzesiek E. Fecal Calprotectin as an activity marker of inflammatory bowel disease in children. Advances in Clinical and Experimental Medicine. 2015;24(5):815–822. doi: 10.17219/acem/26003.
    1. Berni Canani R., Rapacciuolo L., Romano M. T., et al. Diagnostic value of faecal calprotectin in paediatric gastroenterology clinical practice. Digestive and Liver Disease. 2004;36(7):467–470. doi: 10.1016/j.dld.2004.02.009.
    1. Walkiewicz D., Werlin S. L., Fish D., Scanlon M., Hanaway P., Kugathasan S. Fecal calprotectin is useful in predicting disease relapse in pediatric inflammatory bowel disease. Inflammatory Bowel Diseases. 2008;14(5):669–673. doi: 10.1002/ibd.20376.
    1. Joshi S., Lewis S. J., Creanor S., Ayling R. M. Age-related faecal calprotectin, lactoferrin and tumour M2-PK concentrations in healthy volunteers. Annals of Clinical Biochemistry. 2010;47(3):259–263. doi: 10.1258/acb.2009.009061. Pt 3.
    1. Kato J., Hiraoka S., Nakarai A., Takashima S., Inokuchi T., Ichinose M. Fecal immunochemical test as a biomarker for inflammatory bowel diseases: can it rival fecal calprotectin? Intestinal Research. 2016;14(1):5–14. doi: 10.5217/ir.2016.14.1.5.
    1. Hiraoka S., Kato J., Nakarai A., et al. 1075 Consecutive Measurements by Fecal Immunochemical Test in Quiescent Ulcerative Colitis Patients Can Detect Subclinical Relapse. Gastroenterology. 2016;150(4):p. S213. doi: 10.1016/S0016-5085(16)30790-9.
    1. Nakarai A., Kato J., Hiraoka S., et al. Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results, mucosal healing, and risk of relapse. World Journal of Gastroenterology. 2016;22(21):5079–5087. doi: 10.3748/wjg.v22.i21.5079.
    1. Hiraoka S., Kato J., Nakarai A., et al. Consecutive measurements by faecal immunochemical test in quiescent ulcerative colitis patients can detect clinical relapse. Journal of Crohns and Colitis. 2016;10(6):687–694. doi: 10.1093/ecco-jcc/jjw025.
    1. Bodelier A. G. L., Jonkers D., van den Heuvel T., et al. High percentage of IBD patients with indefinite fecal calprotectin levels: additional value of a combination score. Digestive Diseases and Sciences. 2017;62(2):465–472. doi: 10.1007/s10620-016-4397-6.

Source: PubMed

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