Details for Performance of the PRO-C3 Collagen Neo-Epitope Biomarker in Non-Alcoholic Fatty Liver Disease

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Name:Performance of the PRO-C3 Collagen Neo-Epitope Biomarker in Non-Alcoholic Fatty Liver Disease
Description:

Background & Aim:
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.

Methods:
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.

Results:
Plasma PRO-C3 levels correlated with grade of histological steatohepatitis (rs = 0.367, p ≪0.0001) and stage of fibrosis (rs = 0.462, p ≪0.0001), exhibiting similar performance to current fibrosis scores such as FIB4 for the detection of F≥3 fibrosis. FIBC3 exhibited substantially improved accuracy (AUROC 0.89 and 0.83 in the discovery and validation sets, respectively) and outperformed FIB4 and other similar diagnostic panels. The simplified version, ABC3D, was concurrently developed and had comparable diagnostic accuracy (AUROC 0.88 and 0.81 in the discovery and validation sets, respectively).

Conclusion:
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.

Authors:Boyle, M. et al
Journal Title:JHEP Reports
Journal Year:2019
Volume / Issue No.:1(3)
Digital Object Identifier:http://dx.doi.org/10.1016/j.jhepr.2019.06.004
Filename:Boyle_JHEP Reports_Sep2019.pdf
Filesize: 898.52 kB
Filetype:pdf (Mime Type: application/pdf)
Creator:ixscient
Created On: 12/23/2019 10:59
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Maintained by:ixscient
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Last updated on: 12/23/2019 11:01
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