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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 |
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