Performance of the PRO-C3 collagen neo-epitope biomarker in non-alcoholic fatty liver disease.

Biomarker NAFLD NASH PRO-C3 Steatohepatitis fibrosis

Journal

JHEP reports : innovation in hepatology
ISSN: 2589-5559
Titre abrégé: JHEP Rep
Pays: Netherlands
ID NLM: 101761237

Informations de publication

Date de publication:
Sep 2019
Historique:
received: 02 05 2019
revised: 28 05 2019
accepted: 22 06 2019
entrez: 11 2 2020
pubmed: 11 2 2020
medline: 11 2 2020
Statut: epublish

Résumé

There is an unmet need for non-invasive biomarkers in non-alcoholic fatty liver disease (NAFLD) that can diagnose advanced disease and identify patients suitable for clinical trials. The PRO-C3 collagen neo-epitope is a putative direct marker of fibrogenesis. We assessed the performance of PRO-C3 in a large, well-characterised international NAFLD cohort and report the development and validation of 2 novel panels for the diagnosis of advanced fibrosis (F≥3) in NAFLD, including a simplified clinical score which eliminates the need for online calculators. Plasma PRO-C3 levels were determined in a prospectively recruited international cohort of 449 patients with biopsy diagnosed NAFLD across the full disease spectrum (F0: n = 90; F1: 100; F2: 92; F3: 101; F4: 66). The cohort was divided into a discovery group (n = 151) and a validation group (n = 298). Logistic regression was performed to establish complex (FIBC3) and simplified (ABC3D) diagnostic scores that accurately identify advanced fibrosis. Performance for each was compared to established non-invasive fibrosis scoring systems. Plasma PRO-C3 levels correlated with grade of histological steatohepatitis (r Plasma PRO-C3 levels correlate with severity of steatohepatitis and fibrosis stage. The FIBC3 panel is an accurate tool with a single threshold value that maintains both sensitivity and specificity for the identification of F≥3 fibrosis in NAFLD, eliminating indeterminate results and outperforming commonly used non-invasive tools. A greatly simplified version (ABC3D) that is readily amenable to use in the clinic has been validated and shown to perform with similar accuracy, and may prove a useful tool in routine clinical practice. We performed a comprehensive, independent evaluation of a collagen biomarker (PRO-C3) to detect and quantify liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). We report the development of 2 diagnostic panels using PRO-C3 to identify patients with advanced fibrosis, one optimal but more complex to calculate (FIBC3), the other easier to use (ABC3D) whilst still performing well.

Identifiants

pubmed: 32039369
doi: 10.1016/j.jhepr.2019.06.004
pii: S2589-5559(19)30061-8
pmc: PMC7001575
doi:

Types de publication

Journal Article

Langues

eng

Pagination

188-198

Informations de copyright

© 2019 The Authors.

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Auteurs

Marie Boyle (M)

Newcastle Liver Research Group, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom.

Dina Tiniakos (D)

Newcastle Liver Research Group, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
Department of Pathology, Aretaieion Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Jorn M Schattenberg (JM)

I. Department of Medicine, University Medical Centre, Mainz, Germany.

Vlad Ratziu (V)

Institute of Cardiometabolism and Nutrition, Pitié-Salpêtrière Hospital, Paris, France.

Elisabetta Bugianessi (E)

Division of Gastroenterology, Department of Medical Sciences, University of Torino, Torino, Italy.

Salvatore Petta (S)

Sezione di Gastroenterologia, Di.Bi.M.I.S., University of Palermo, Italy.

Claudia P Oliveira (CP)

Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil.

Olivier Govaere (O)

Newcastle Liver Research Group, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.

Ramy Younes (R)

Newcastle Liver Research Group, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
Division of Gastroenterology, Department of Medical Sciences, University of Torino, Torino, Italy.

Stuart McPherson (S)

Newcastle Liver Research Group, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom.

Pierre Bedossa (P)

Newcastle Liver Research Group, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.

Mette J Nielsen (MJ)

Nordic Bioscience A/S, Biomarkers and Research, Herlev, Denmark.

Morten Karsdal (M)

Nordic Bioscience A/S, Biomarkers and Research, Herlev, Denmark.

Diana Leeming (D)

Nordic Bioscience A/S, Biomarkers and Research, Herlev, Denmark.

Stuart Kendrick (S)

GlaxoSmithKline Research & Development Ltd, Stevenage, UK.

Quentin M Anstee (QM)

Newcastle Liver Research Group, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom.

Classifications MeSH