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P268 Fecal calprotectin correlates more highly with endoscopic disease activity than symptom-based disease activity markers in paediatric PSC-IBD

Ricciuto A., Fish J., Carman N., Crowley E., Muise A., Church P., Walters T., Kamath B.M., Griffiths A.

Hospital for Sick Children, University of Toronto, Toronto, Canada

Background

Inflammatory bowel disease (IBD) with primary sclerosing cholangitis (PSC) has a distinct phenotype, with mild symptoms despite pancolitis and frequent backwash ileitis. The well-known greater risk of colonic neoplasia (where chronic inflammatory activity is a risk factor) led us to hypothesize that symptoms might be an inaccurate reflection of endoscopic disease activity in children with PSC-IBD.

Methods

In this single-centre prospective study, Paediatric UC Activity Index (PUCAI), physician global assessment (PGA) and fecal calprotectin (FC) were measured in all PSC-IBD patients undergoing colonoscopy. Patients with colonic IBD without PSC served as controls. Colonoscopies were scored by two blinded IBD physicians using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and endoscopic PGA. Spearman correlations were calculated between variables. PUCAI and FC were compared between patients in and not in endoscopic remission (UCEIS 0–2), in both groups.

Results

24 PSC-IBD and 32 colonic IBD patients were enrolled (Table 1). Median PUCAI and FC at colonoscopy were 2.5 (range 0–70) and 348 (37–8252) μg/g in PSC-IBD patients, and 15 (range 0–75) and 1435 (range 29–16782) μg/g in colonic IBD patients, respectively. As hypothesized, the correlations between symptom-based assessments of disease activity and endoscopy were poor in PSC-IBD patients (r=0.421 for PUCAI, r=0.196 for clinical PGA vs. UCEIS) (Table 2). The correlation between FC and UCEIS was significantly better (r=0.782). FC correlated poorly with both PUCAI and clinical PGA. In contrast, PUCAI correlated well with UCEIS in controls (r=0.824); this correlation was superior to that of FC vs. UCEIS (r=0.696). The correlation between PUCAI and FC was better in controls than in PSC-IBD patients (r=0.525 vs. 0.367). FC and PUCAI differed significantly based on endoscopic remission status in controls, but only FC differed in PSC-IBD patients (Table 1).

Table 1. Patient and disease characteristics

% or median (IQR)PSC-IBD (n=24)Colonic IBD
Male67%53%
Age at IBD diagnosis (years)12.1 (4.0–13.6)12.7 (7.8–14.7)
Pancolitis79%71%
Relative rectal sparing35%12.5%
Backwash ileitis35%12.5%
Age at PSC diagnosis (years)12.6 (IQR 9.2–14.4)
Autoimmune hepatitis overlap43%
FC by endoscopic remission status (in remission vs. not)92 (IQR 42–32) vs. 2539 (IQR 2205–7606), p=0.002282 (IQR 75–760) vs. 2795 (IQR 1896–13585), p=0.002
PUCAI by endoscopic remission status (in remission vs. not)0 (IQR 0–10) vs. 17.5 (IQR 0–30), p=0.150 (IQR 0–0) vs. 35 (IQR 24–42.5), p≤0.001

Table 2. Spearman correlations between symptom-, biomarker- and endoscopy-based markers of disease activity in paediatric PSC-IBD

PUCAIClinical PGAFCCRPUCEISEndoscopic PGA
PUCAI1.00.73 (p=0.0018)0.37 (p=0.27)0.64 (p=0.008)0.42 (p=0.07)0.40 (p=0.08)
Clinical PGA0.73 (p=0.002)1.0−0.03 (p=0.95)0.32 (p=0.31)0.20 (p=0.50)0.25 (p=0.36)
FC0.37 (p=0.27)−0.03 (p=0.95)1.00.76 (p=0.02)0.78 (p=0.004)0.82 (p=0.002)
CRP0.64 (p=0.008)0.32 (p=0.31)0.76 (p=0.02)1.00.85 (p<0.001)0.80 (p<0.001)
UCEIS0.42 (p=0.07)0.20 (p=0.50)0.78 (p=0.004)0.85 (p<0.001)1.00.98 (p<0.001)
Endoscopic PGA0.40 (p=0.08)0.25 (p=0.36)0.82 (p=0.002)0.80 (p<0.0010.98 (p<0.001)1.0

Conclusion

Absence of symptoms cannot be relied on to reflect endoscopic activity in paediatric PSC-IBD. FC appears to be more accurate in this setting. Given the emerging importance of the gut-liver axis in PSC, increasing attention must be paid to achieving mucosal healing, particularly in children in early phases of PSC, where the possibility of altering biliary disease progression may be greatest.