Discovery, validation and sequencing of urinary peptides for diagnosis of liver fibrosis—A multicentre study

Autor: Ayman S. Bannaga, Jochen Metzger, Ioannis Kyrou, Torsten Voigtländer, Thorsten Book, Jesus Melgarejo, Agnieszka Latosinska, Martin Pejchinovski, Jan A. Staessen, Harald Mischak, Michael P. Manns, Ramesh P. Arasaradnam
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: EBioMedicine, Vol 62, Iss , Pp 103083- (2020)
Druh dokumentu: article
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2020.103083
Popis: Background: Liver fibrosis is a consequence of chronic inflammation and is associated with protein changes within the hepatocytes structure. In this study, we aimed to investigate if this is reflected by the urinary proteome and can be explored to diagnose liver fibrosis in patients with chronic liver disease. Methods: In a multicentre combined cross-sectional and prospective diagnostic test validation study, 129 patients with varying degrees of liver fibrosis and 223 controls without liver fibrosis were recruited. Additionally, 41 patients with no liver, but kidney fibrosis were included to evaluate interference with expressions of kidney fibrosis. Urinary low molecular weight proteome was analysed by capillary electrophoresis coupled to mass spectrometry (CE-MS) and a support vector machine marker model was established by integration of peptide markers for liver fibrosis. Findings: CE-MS enabled identification of 50 urinary peptides associated with liver fibrosis. When combined into a classifier, LivFib-50, it separated patients with liver fibrosis (N = 31) from non-liver disease controls (N = 123) in cross-sectional diagnostic phase II evaluation with an area under the curve (AUC) of 0.94 (95% confidence intervals (CI): 0.89–0.97, p
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