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Systematic review with meta-analysis: Diagnostic accuracy of Pro-C3 for hepatic fibrosis in patients with non-alcoholic fatty liver disease

Lookup NU author(s): Professor Quentin AnsteeORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2021 by the authors. Licensee MDPI, Basel, Switzerland. The prevalence and severity of non-alcoholic fatty liver disease (NAFLD) is increasing, yet adequately validated tests for care paths are limited and non-invasive markers of disease progression are urgently needed. The aim of this work was to summarize the performance of Pro-C3, a biomarker of active fibrogenesis, in detecting significant fibrosis (F ≥ 2), advanced fibrosis (F ≥ 3), cirrhosis (F4) and non-alcoholic steatohepatitis (NASH) in patients with NAFLD. A sensitive search of five databases was performed in July 2021. Studies reporting Pro-C3 measurements and liver histology in adults with NAFLD without co-existing liver diseases were eligible. Meta-analysis was conducted by applying a bivariate random effects model to produce summary estimates of Pro-C3 accuracy. From 35 evaluated reports, eight studies met our inclusion criteria; 1568 patients were included in our meta-analysis of significant fibrosis and 2058 in that of advanced fibrosis. The area under the summary curve was 0.81 (95% CI 0.77–0.84) in detecting significant fibrosis and 0.79 (95% CI 0.73–0.82) for advanced fibrosis. Our results support Pro-C3 as an important candidate biomarker for non-invasive assessment of liver fibrosis in NAFLD. Further direct comparisons with currently recommended non-invasive tests will demonstrate whether Pro-C3 panels can outperform these tests, and improve care paths for patients with NAFLD.

Publication metadata

Author(s): Mak AL, Lee J, van Dijk A-M, Vali Y, Aithal GP, Schattenberg JM, Anstee QM, Brosnan MJ, Zafarmand MH, Ramsoekh D, Harrison SA, Nieuwdorp M, Bossuyt PM, Holleboom AG

Publication type: Review

Publication status: Published

Journal: Biomedicines

Year: 2021

Volume: 9

Issue: 12

Online publication date: 15/12/2021

Acceptance date: 10/12/2021

ISSN (electronic): 2227-9059

Publisher: MDPI


DOI: 10.3390/biomedicines9121920