Accuracy of Faecal Calprotectin and Neutrophil Gelatinase B-associated Lipocalin in Evaluating Subclinical Inflammation in UlceRaTIVE Colitis-the ACERTIVE study.
OBJECTIVE
Mucosal healing and histological remission are different targets for patients with ulcerative colitis, but both rely on an invasive endoscopic procedure. This study aimed to assess faecal calprotectin and neutrophil gelatinase B-associated lipocalin as biomarkers for disease activity in asymptomatic ulcerative colitis patients.


METHODS
This was a multicentric cross-sectional study including 371 patients, who were classified according to their endoscopic and histological scores. These results were evaluated alongside the faecal levels of both biomarkers.


RESULTS
Macroscopic lesions [i.e. endoscopic Mayo score ≥1] were present in 28% of the patients, and 9% had active disease according to fht Ulcerative Colitis Endoscopic Index of Severity. Moreover, 21% presented with histological inflammation according to the Geboes index, whereas 15% and 5% presented with focal and diffuse basal plasmacytosis, respectively. The faecal levels of calprotectin and neutrophil gelatinase B-associated lipocalin were statistically higher for patients with endoscopic lesions and histological activity. A receiver operating characteristic-based analysis revealed that both biomarkers were able to indicate mucosal healing and histological remission with an acceptable probability, and cut-off levels of 150-250 μg/g for faecal calprotectin and 12 μg/g for neutrophil gelatinase B-associated lipocalin were proposed.


CONCLUSIONS
Faecal calprotectin and neutrophil gelatinase B-associated lipocalin levels are a valuable addition for assessment of disease activity in asymptomatic ulcerative colitis patients. Biological levels of the analysed biomarkers below the proposed thresholds can rule out the presence of macroscopic and microscopic lesions with a probability of 75-93%. However, caution should be applied whenever interpreting positive results, as these biomarkers present consistently low positive predictive values.
Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar São João, Porto, Portugal.|Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.|MedInUP, Centre for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal.
Fernando
F
Magro
Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar São João, Porto, Portugal.
Susana
S
Lopes
Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar São João, Porto, Portugal.
Rosa
R
Coelho
Department of Gastroenterology, Hospital da Senhora da Oliveira, Guimarães, Portugal.
José
J
Cotter
Department of Gastroenterology, Hospital da Senhora da Oliveira, Guimarães, Portugal.
Francisca
F
Dias de Castro
Department of Gastroenterology, Centro Hospitalar do Algarve - Portimão Unit, Portimão, Portugal.|Departament of Medicine and Medical Biosciences, University of Algarve, Faro, Portugal.
Helena
H
Tavares de Sousa
Department of Gastroenterology, Centro Hospitalar do Porto, Hospital de Santo António, Portugal.
Marta
M
Salgado
Department of Gastroenterology, Faculty of Medicine, Centro Hospitalar São João, Porto, Portugal.
Patrícia
P
Andrade
Department of Gastroenterology, Hospital Garcia de Orta, Almada, Portugal.
Ana Isabel
AI
Vieira
Department of Gastroenterology, Hospital Garcia de Orta, Almada, Portugal.
Pedro
P
Figueiredo
Department of Gastroenterology, Centro Hospitalar do Algarve, Faro, Portugal.
Paulo
P
Caldeira
Department of Gastroenterology, Centro Hospitalar do Algarve, Faro, Portugal.
A
A
Sousa
Department of Gastroenterology, Divino Espírito Santo Hospital, Ponta Delgada, Portugal.
Maria A
MA
Duarte
Department of Gastroenterology, Divino Espírito Santo Hospital, Ponta Delgada, Portugal.
Filipa
F
Ávila
Department of Gastroenterology, Instituto Português do Oncologia de Lisboa, Lisboa, Portugal.
João
J
Silva
Department of Gastroenterology, Instituto Português do Oncologia de Lisboa, Lisboa, Portugal.
Joana
J
Moleiro
Department of Gastroenterology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
Sofia
S
Mendes
Department of Gastroenterology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
Sílvia
S
Giestas
Department of Gastroenterology, Centro Hospitalar Tondela-Viseu, Viseu, Portugal.
Paula
P
Ministro
Department of Gastroenterology, Centro Hospitalar Tondela-Viseu, Viseu, Portugal.
Paula
P
Sousa
Department of Gastroenterology, Hospital de Braga, Braga, Portugal.
Raquel
R
Gonçalves
Department of Gastroenterology, Hospital de Braga, Braga, Portugal.
Bruno
B
Gonçalves
Department of Gastroenterology, Hospital Fernando Fonseca, Amadora, Portugal.
Ana
A
Oliveira
Department of Gastroenterology, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal.
Cristina
C
Chagas
Department of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal.
Joana
J
Torres
CIDES - Department of Health Information and Decision Sciences, Faculty of Medicine, University of Porto, Porto, Portugal.|CINTESIS, Center for Health Technology and Services Research, Porto, Portugal.
Cláudia Camila
CC
Dias
Department of Pathology, Centro Hospitalar São João, Porto, Portugal.
Joanne
J
Lopes
Institute of Pathology, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
Paula
P
Borralho
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.|MedInUP, Centre for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal.
Joana
J
Afonso
Department of Pathology, University Hospital of KU Leuven and UZ Gent, Leuven, Belgium.
Karel
K
Geboes
Department of Pathology, Centro Hospitalar São João, Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto [Ipatimup], University of Porto, Porto, Portugal.
Fátima
F
Carneiro
D000328:Adult; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000473:pathology; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis* / Q000378:metabolism; D000071068:Lipocalin-2 / Q000032:analysis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000737:chemistry* / Q000378:metabolism
D039841:Leukocyte L1 Antigen Complex; D000071068:Lipocalin-2
Endoscopic and histological remission; faecal markers; ulcerative colitis