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

Publication ,  Journal Article
Nielsen, MJ; Dolman, GE; Harris, R; Frederiksen, P; Chalmers, J; Grove, JI; Irving, WL; Karsdal, MA; Patel, K; Leeming, DJ; Guha, IN
Published in: JHEP Reports
June 1, 2023

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.

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Published In

JHEP Reports

DOI

EISSN

2589-5559

Publication Date

June 1, 2023

Volume

5

Issue

6

Related Subject Headings

  • 3202 Clinical sciences
 

Citation

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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). https://doi.org/10.1016/j.jhepr.2023.100743
Nielsen, M. J., G. E. Dolman, R. Harris, P. Frederiksen, J. Chalmers, J. I. Grove, W. L. Irving, et al. “PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease.” JHEP Reports 5, no. 6 (June 1, 2023). https://doi.org/10.1016/j.jhepr.2023.100743.
Nielsen MJ, Dolman GE, Harris R, Frederiksen P, Chalmers J, Grove JI, et al. PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease. JHEP Reports. 2023 Jun 1;5(6).
Nielsen, M. J., et al. “PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease.” JHEP Reports, vol. 5, no. 6, June 2023. Scopus, doi:10.1016/j.jhepr.2023.100743.
Nielsen MJ, Dolman GE, Harris R, Frederiksen P, Chalmers J, Grove JI, Irving WL, Karsdal MA, Patel K, Leeming DJ, Guha IN. PRO-C3 is a predictor of clinical outcomes in distinct cohorts of patients with advanced liver disease. JHEP Reports. 2023 Jun 1;5(6).
Journal cover image

Published In

JHEP Reports

DOI

EISSN

2589-5559

Publication Date

June 1, 2023

Volume

5

Issue

6

Related Subject Headings

  • 3202 Clinical sciences