Systematic Review with Meta-Analysis: Diagnostic Accuracy of Pro-C3 for Hepatic Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease
Anne Linde Mak,
Jenny Lee,
Anne-Marieke van Dijk,
Yasaman Vali,
Guruprasad P. Aithal,
Jörn M. Schattenberg,
Quentin M. Anstee,
M. Julia Brosnan,
Mohammad Hadi Zafarmand,
Dewkoemar Ramsoekh,
Stephen A. Harrison,
Max Nieuwdorp,
Patrick M. Bossuyt,
Adriaan G. Holleboom
Affiliations
Anne Linde Mak
Department of Vascular Medicine, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
Jenny Lee
Department of Epidemiology and Data Science, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
Anne-Marieke van Dijk
Department of Vascular Medicine, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
Yasaman Vali
Department of Epidemiology and Data Science, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
Guruprasad P. Aithal
NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK
Jörn M. Schattenberg
Metabolic Liver Research Program, Department of Medicine, University Medical Centre, Johannes Gutenberg University, 55131 Mainz, Germany
Quentin M. Anstee
The Newcastle Liver Research Group, Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
M. Julia Brosnan
Internal Medicine Research Unit, Pfizer Inc., Cambridge, MA 02139, USA
Mohammad Hadi Zafarmand
Department of Epidemiology and Data Science, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
Dewkoemar Ramsoekh
Department of Gastroenterology and Hepatology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
Stephen A. Harrison
Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK
Max Nieuwdorp
Department of Vascular Medicine, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
Patrick M. Bossuyt
Department of Epidemiology and Data Science, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
Adriaan G. Holleboom
Department of Vascular Medicine, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands
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.
