Background and Aims
Histologic remission has arisen as the optimal treatment outcome in Ulcerative colitis (UC). The aim of this retrospective study was to explore the diagnostic performance of the non-invasive fecal biomarkers Calprotectin (FC) and Lactoferrin (FL) compared to the histological indices Nancy Index (NI) and Riley Index (RI).
Methods
This study is a retrospective diagnostic accuracy study based on secondary analysis of patient data from 2002–2017 extracted from medical registries of our clinics in Essen-Mitte, Germany. UC patients underwent a colonoscopy, with biopsies taken from the rectum and the sigmoid scored by two experienced pathologists according to NI and RI and provided a stool sample within seven days pre- or post-colonoscopy. Diagnostic accuracy of recommended cut-offs for FC (>50μg/g) and FL (≥7.25μg/g) were tested against our reference standard (NI ≥2) in terms of specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and accuracy (effectiveness).
Results
The number of UC patients recruited was n = 226, aged 45.2 (SD 13.3). Histological indices were highly correlated (r 0.980, p <.001). Fecal biomarkers correlated moderately with NI (FC: r 0.383, p <.001; FL: r 0.420, p <.001) and RI (FC: r 0.395, p <.001; FL: r 0.424, p <.001). Fecal biomarker concentrations were increased in patients with active histological disease (NI ≥ 2), Median[IQR]; FC 69.72 [20.07–254.38]; FL 18.59 [6.06–44.42], compared to those with inactive disease (NI ≤1), FC 12.35 [3.89 – 32.16]; FL 3.14 [0.75–11.05]; z = -6.60, p < .001. Fecal biomarker concentrations differed significantly across NI Grades 0–4 (FC: H4 = 45.2; FL: H4 = 47.5, both p < .001). Patients with Grade 0 had significantly lower concentrations of fecal biomarkers than those with Grade 3 (Median; FC 10.94 vs. 72.22; FL 2.30 vs. 29.10; both p < .001) or Grade 4 (FC 10.94 vs. 67.00; FL 2.30 vs. 27.64; both p < .001), as well as Grade 2 for FC only (10.94 vs. 56.22, p = .001). Concentrations were also lower in patients with Grade 1 compared to those with Grade 3 (FC 17.49 vs. 72.22; FL 4.24 vs. 29.10; both p < .001) or Grade 4 (FC 17.49 vs. 67.00; FL 4.24 vs. 27.64; both p < .001). ROC AUC showed moderate diagnostic accuracy for both FC 0.76 (95%CI 0.70, 0.83) and FL 0.73 (95%CI 0.66, 0.80). Optimised cut-offs for FC (≥ 34.29) and FL (≥ 5.85μg/g) both had slightly improved accuracy, compared with the manufacturer’s cut-offs (FC: 69.9% vs. 65.9%; FL: 71.7% vs. 69.0%).
Conclusions
Fecal biomarkers calprotectin and lactoferrin correlate with histologic disease activity and differentiate between patients in histologic remission from those with evidence of moderate to severe disease activity. Their non-invasiveness, in addition to being inexpensive supports their use in the clinical monitoring of patients with UC.
