Evidence map›Paper›PMID 27861569›Full record

ArticlePloS one2016

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.

Katharine M Irvine, Leesa F Wockner, Isabell Hoffmann, Leigh U Horsfall, Kevin J Fagan, Veonice Bijin, Bernett Lee, Andrew D Clouston, Guy Lampe, John E Connolly and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

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  18. Molecular characterization of a precision-cut rat liver slice model for the evaluation of antifibrotic compounds.American journal of physiology. Gastrointestinal and liver physiology · 2019
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 3 countries.

Katharine M IrvineCentre for Liver Disease Research, School of Medicine, The University of Queensland, Brisbane, Australia.
Leesa F WocknerStatistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Isabell HoffmannStatistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Leigh U HorsfallCentre for Liver Disease Research, School of Medicine, The University of Queensland, Brisbane, Australia.
Kevin J FaganCentre for Liver Disease Research, School of Medicine, The University of Queensland, Brisbane, Australia.
Veonice BijinInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673; Singapore Immunology Network, Singapore 138648; and Institute of Biomedical Studies, Baylor University, Waco, Texas, 76798, United States of America.
Bernett LeeInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673; Singapore Immunology Network, Singapore 138648; and Institute of Biomedical Studies, Baylor University, Waco, Texas, 76798, United States of America.
Andrew D CloustonCentre for Liver Disease Research, School of Medicine, The University of Queensland, Brisbane, Australia.
Guy LampePathology Queensland, Princess Alexandra Hospital, Brisbane, Australia.
John E ConnollyInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673; Singapore Immunology Network, Singapore 138648; and Institute of Biomedical Studies, Baylor University, Waco, Texas, 76798, United States of America.
Elizabeth E PowellCentre for Liver Disease Research, School of Medicine, The University of Queensland, Brisbane, Australia.
The University of Queensland · AUBaylor University · USPrincess Alexandra Hospital · AUQIMR Berghofer Medical Research Institute · AUInstitute of Molecular and Cell Biology · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsNon-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.

methodsWe 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.

resultsSeventeen 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).

conclusionsWe 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.

Indexed as

Blood ProteinsAdultBiomarkersCross-Sectional StudiesEnzyme-Linked Immunosorbent AssayFemaleHumansLiver CirrhosisLogistic ModelsMaleMiddle AgedReproducibility of ResultsRetrospective StudiesSeverity of Illness IndexBiomarkersBlood Proteins

Identifiers

PMID27861569
PMCPMC5115865
OpenAlexW2556346141

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.