Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0167001
Title: Multiplex serum protein analysis identifies novel biomarkers of advanced fibrosis in patients with chronic liver disease with the potential to improve diagnostic accuracy of established biomarkers
Authors: Irvine K.M.
Wockner L.F.
Hoffmann I.
Horsfall L.U.
Fagan K.J.
Bijin V.
Lee B.
Clouston A.D.
Lampe G.
Connolly J.E. 
Powell E.E.
Keywords: adipocytokine
alanine aminotransferase
alpha fetoprotein
aspartate aminotransferase
biological marker
cytokine
hyaluronic acid
interleukin 8
interstitial collagenase
matrilysin
platelet derived growth factor AA
procollagen type 3 aminopropeptide
tissue inhibitor of metalloproteinase 1
biological marker
plasma protein
adult
age
analytical parameters
Article
aspartate aminotransferase platelet ratio index
body mass
chronic liver disease
cohort analysis
controlled study
cross-sectional study
diabetes mellitus
diagnostic accuracy
diagnostic test accuracy study
disease activity
disease association
disease severity
enzyme linked immunosorbent assay
fatty liver
female
hepatitis
human
immunoassay analyzer
liver biopsy
liver fibrosis
major clinical study
male
middle aged
predictive value
protein analysis
protein blood level
receiver operating characteristic
retrospective study
sensitivity and specificity
blood
liver cirrhosis
reproducibility
severity of illness index
statistical model
Adult
Biomarkers
Blood Proteins
Cross-Sectional Studies
Enzyme-Linked Immunosorbent Assay
Female
Humans
Liver Cirrhosis
Logistic Models
Male
Middle Aged
Reproducibility of Results
Retrospective Studies
Severity of Illness Index
Issue Date: 2016
Publisher: Public Library of Science
Citation: Irvine K.M., Wockner L.F., Hoffmann I., Horsfall L.U., Fagan K.J., Bijin V., Lee B., Clouston A.D., Lampe G., Connolly J.E., Powell E.E. (2016). Multiplex serum protein analysis identifies novel biomarkers of advanced fibrosis in patients with chronic liver disease with the potential to improve diagnostic accuracy of established biomarkers. PLoS ONE 11 (11) : 167001. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0167001
Abstract: Background and Aims Non-invasive markers of liver fibrosis are urgently required, especially for use in non-specialist settings. The aim of this study was to identify novel serum biomarkers of advanced fibrosis. Methods We performed an unbiased screen of 120 serum analytes including cytokines, chemokines and proteases in 70 patients (35 without fibrosis, 35 with cirrhosis on biopsy), and selected a panel of 44 candidate biomarkers, which were subsequently measured in a mixed-etiology cohort of 432 patients with known serum HA, PIIINP and TIMP1 (which comprise the validated Enhanced Liver Fibrosis (ELF) test). Multivariate logistic regression modelling was used to generate models for the prediction of advanced or significant fibrosis (METAVIR ?F3 and ?F2, respectively); in addition to identifying biomarkers of disease activity and steatohepatitis. Results Seventeen analytes were significantly differentially expressed between patients with no advanced fibrosis and patients with advanced fibrosis, the most significant being hyaluronic acid (HA) and matrix metalloproteinase (MMP) 7 (p = 2.9E-41 and p = 1.0E-26, respectively). The optimal model for the prediction of advanced fibrosis comprised HA, MMP7, MMP1, alphafetoprotein (AFP) and the AST to platelet ratio index (APRI). We demonstrate enhanced diagnostic accuracy (AUROC = 0.938) compared to a model comprising HA, PIIINP and TIMP1 alone (ELF) (AUROC = 0.898, p<0.0001, De Long's test). Conclusions We have identified novel serum biomarkers of advanced liver fibrosis, which have the potential to enhance the diagnostic accuracy of established biomarkers. Our data suggest MMP7 is a valuable indicator of advanced fibrosis and may play a role in liver fibrogenesis. © 2016 Irvine et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/166034
ISSN: 19326203
DOI: 10.1371/journal.pone.0167001
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_pone_0167001.pdf1.01 MBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.