Assessing Histological Inflammatory Activity in Patients With Ulcerative Colitis: A Diagnostic Accuracy Study Testing Fecal Biomarkers Lactoferrin and Calprotectin
Authors: Langhorst Jost , Kairey Lana , Oberle Angela , Boone James , Dobos Gustav , Juette Hendrik , Tannapfel Andrea , Rueffer Andreas 
Published: June 2020

Background and Aims

Histological 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 noninvasive 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 to 2017 extracted from medical registries of our clinics in Essen-Mitte, Germany. Patients with UC underwent a colonoscopy, with biopsies taken from the rectum and the sigmoid scored by 2 experienced pathologists according to NI and RI and provided a stool sample within 7 days pre- or post-colonoscopy. Diagnostic accuracy of recommended cutoffs for FC (&gt;50 μg/g) and FL (≥7.25 μg/g) were tested against our reference standard (NI ≥2) in terms of specificity, sensitivity, positive predictive value, negative predictive value, and accuracy (effectiveness).

Results

The number of patients with UC recruited was n = 226, aged 45.2 (SD 13.3). Histological indices were highly correlated (r = 0.980, P &lt; 0.001). Fecal biomarkers correlated moderately with NI (FC: r = 0.383, P &lt; 0.001; FL: r = 0.420, P &lt; 0.001) and RI (FC: r = 0.395, P &lt; 0.001; FL: r = 0.424, P &lt; 0.001). 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 &lt; 0.001. Fecal biomarker concentrations differed significantly across NI grades 0–4 (FC: H4 = 45.2; FL: H4 = 47.5, both P &lt; 0.001). 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 &lt; 0.001) or grade 4 (FC 10.94 vs 67.00; FL 2.30 vs 27.64; both P &lt; 0.001), as well as grade 2 for FC only (10.94 vs 56.22, P = 0.001). 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 ≤ 0.001) or grade 4 (FC 17.49 vs 67.00; FL 4.24 vs 27.64; both P &lt; 0.001).

Receiver operating characteristics area under the curve showed moderate diagnostic accuracy for both FC 0.76 (95% confidence interval [CI] 0.70–0.83) and FL 0.73 (95% CI 0.66–0.80). Optimized cutoffs for both FC (≥34.29) and FL (≥5.85 μg/g) had slightly improved accuracy, compared with the manufacturer’s cutoffs (FC: 69.9% vs 65.9%; FL: 71.7% vs 69.0%).

Conclusions

Fecal biomarkers calprotectin and lactoferrin correlate with histological disease activity and differentiate between patients in histological remission from those with evidence of moderate to severe disease activity. Their noninvasiveness, in addition to being inexpensive, supports their use in the clinical monitoring of patients with UC.