PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease

Nielsen, Mette J.; Dolman, Grace E.; Harris, Rebecca; Frederiksen, Peder; Chalmers, Jane; Grove, Jane I.; Irving, William L.; Karsdal, Morten A.; Patel, Keyur; Leeming, Diana Julie; Guha, Indra Neil

Abstract

Background & Aims: Fibroblast activity is a key feature of fibrosis progression and organ function loss, leading to liver-related complications and mortality. The fibrogenesis marker, PRO-C3, has been shown to have prognostic significance in relation to fibrosis progression and as a treatment efficacy marker. We investigated whether PRO-C3 was prognostic for clinical outcome and mortality in two distinct cohorts of compensated cirrhosis.

Methods: Cohort 1 was a rapid fibrosis progression cohort including 104 patients with HCV and biopsy-proven Ishak fibrosis stage ≥3 without prior clinical events. Cohort 2 was a prospective cohort including 172 patients with compensated cirrhosis of mixed aetiology. Patients were assessed for clinical outcomes. PRO-C3 was assessed in serum at baseline in cohorts 1 and 2, and compared with model for end-stage liver disease and albumin–bilirubin (ALBI) scores.

Results: In cohort 1, a 2-fold increase in PRO-C3 was associated with 2.7-fold increased hazard of liver-related events (95% CI 1.6–4.6), whereas a one unit increase in ALBI score was associated with a 6.5-fold increased hazard (95% CI 2.9–14.6). In cohort 2, a 2-fold increase in PRO-C3 was associated with a 2.7-fold increased hazard (95% CI 1.8–3.9), whereas a one unit increase in ALBI score was associated with a 6.3-fold increased hazard (95% CI 3.0–13.2). A multivariable Cox regression analysis identified PRO-C3 and ALBI as being independently associated with the hazard of liver-related outcomes.

Conclusions: PRO-C3 and ALBI were independent prognostic factors for predicting liver-related clinical outcomes. Understanding the dynamic range of PRO-C3 might enhance its use for both drug development and clinical practice.

Impact and Implications: We tested novel proteins of liver scarring (PRO-C3) in two groups of liver patients with advanced disease to see if they could predict clinical events. We found that this marker and an established test called ALBI were both independently associated with future liver-related clinical outcomes.

Citation

Nielsen, M. J., Dolman, G. E., Harris, R., Frederiksen, P., Chalmers, J., Grove, J. I., …Guha, I. N. (2023). PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease. JHEP Reports, 5(6), Article 100743. https://doi.org/10.1016/j.jhepr.2023.100743

• Journal Article Type: Article
• Acceptance Date: Mar 15, 2023
• Online Publication Date: Mar 27, 2023
• Publication Date: 2023-06
• Deposit Date: Mar 28, 2023
• Publicly Available Date: Apr 25, 2023
• Journal: JHEP Reports
• Electronic ISSN: 2589-5559
• Publisher: Elsevier BV
• Peer Reviewed: Peer Reviewed
• Volume: 5
• Issue: 6
• Article Number: 100743
• DOI: https://doi.org/10.1016/j.jhepr.2023.100743
• Keywords: Cirrhosis; Biomarker; Outcome; Extracellular matrix
• Public URL: https://nottingham-repository.worktribe.com/output/18524970
• Publisher URL: https://www.jhep-reports.eu/article/S2589-5559(23)00074-5/fulltext
• Additional Information: This article is maintained by: Elsevier; Article Title: PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease; Journal Title: JHEP Reports; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.jhepr.2023.100743; Content Type: article; Copyright: © 2023 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).