Fecal Calprotectin Predicts the Clinical Course of Acute Severe Ulcerative Colitis R2 이 홍 주 Am J Gastroenterol 2009 ; 104 : 673 ~ 678

INTRODUCTION ASUC (Acute severe ulcelative colitis) profuse bloody diarrhea + systemic upset (fever, tachycardia, and weight loss) major cause of morbidity and mortality in IBD 15% of patients with UC 30~40% of severe attacks : fail to medical therapy → emergency colectomy. overall 3-year mortality rates : 13 % second-line medical therapy (infliximab or cyclosporin) in ASUC surgery (emergency colectomy)

INTRODUCTION Prognostic models (Ho-index, Travis and Lindgren criteria) identifying patients at high risk of failed medical therapy and thereby requiring early surgical intervention → reliable biomarkers Calprotectin (normal value<50ug/g) 36kDa calcium and zinc-binding protein 60% of the protein in the cytosol of neutrophils Active UC and Crohn’s disease : ↑migration of neutrophils (> X10) from circulation to intestine FC : attractive noninvasive candidate biomarker in ASUC diagnostic assay to identify infammatory diarrhea index of therapeutic response in IBD

INTRODUCTION failure to reduce FC = inadequate medical therapy = strong predictor of relapse in both UC and Crohn’s disease within 1 year of follow-up sensitivity : 90 % specificity : 83 % Hypothesis : high FC levels can predict failure of medical therapy in ASUC

METHODS Patients / settings 550,000 Patients : recruited IBD center of Western General Hospital in-patient management of ASUC January 2005 ~ September patients (FC data : 90 patients) Management IV corticosteroid therapy (MPD 60 mg/24 h) high Ho-index or satisfying Travis criteria at day 3 clinical response early surgery (colectomy) or SC therapy : 5 – 7 days second-line medical therapy (infliximab) oral PDL : 40 mg/day

Data collection and case definitions ASUC (modified Truelove and Witts criteria) ≥ 6 episodes of bloody diarrhea/24 h + one or more of the following features anemia (Hb<10.5 g / dl) fever (>37.8 °C) tachycardia (pulse >90/min) elevated ESR (>30 mm/h)) Definition of outcomes Outcome 1 : Colectomy vs. no colectomy. Outcome 2 : Corticosteroid nonresponders vs. responders. Outcome 3 : Infliximab nonresponders vs. responders.METHODS

Statistical analysis Univariate analyses - Mann-Whitney and Fisher’s exact tests P value < 0.05 → significant ROC analysis - sensitivity, specificity, likelihood ratio for FC Kaplan-Meier survival analysis multivariate analysis and conjunction with significant univariate parameters SPSS(Minitab Version 13 and GraphPad InStat)METHODS

RESULTS Patient details Table 1a. The demographics and management of current cohort of acute severe UC 11 (52.4 %):emergency colectomy (median time following infliximab to colectomy : 5 days)

Table 1b. Univariate analysis of the clinical parameters between patients who responded to medical therapy (no colectomy) and patients who had to undergo colectomy during hospitalization (colectomy) Median value (On adm.) ( ) 10.3 ( ) ( ) 27.5 ( ) 36.0 ( ) 40.0 ( ) 4.3 ( )

Figure 1. Scatterplot of fecal calprotectin levels, median calprotectin was 1,020.0ug/g (interquartile range, IQR: – 1,617.5).

Table 2. Fecal calprotectin levels in the three major outcome groups (no colectomy vs. colectomy, corticosteroid responders vs. nonresponders, and infl iximab responders vs. nonresponders)

Figure 2. Receiver – operator characteristic(ROC) curve for fecal calprotectin levels in predicting colectomy within hospitalization (area under the curve = 0.65; P = 0.04).

Table 3. The utility of FC and albumin/CRP measurements in predicting colectomy

CONCLUSIONS This is the first data set to demonstrate that FC levels are dramatically elevated in severe UC. These data raise the possibility that this biomarker can predict response to first or second-line medical therapy in this setting.