Serum markers of fibroinflammatory activity PRO-C3 and CPa9-HNE are associated with liver-related outcomes in patients with Chronic Hepatitis C

BACKGROUND: Chronic hepatitis C (CHC) infection remains a global health burden, contributing to the risk of long-term complications such as progressive fibrosis, cirrhosis, and hepatocellular carcinoma, particularly in undiagnosed or untreated individuals. Novel biomarkers for the assessment of disease progression and prognosis are required for fibroinflammatory chronic liver disease. Our study population from the Hepatitis C Antiviral Long Term Treatment Against Cirrhosis (HALT-C) trial was used to investigate the association of neoepitope fibroinflammatory biomarkers with clinical outcomes in patients with CHC infection.

METHODS: Baseline serum samples from 339 patients with advanced CHC from the HALT-C cohort were included and assessed for liver-related clinical outcomes. We assessed the fibrogenesis marker nordicPRO-C3™ and the neutrophil activity marker nordicCPa9-HNE™.

RESULTS: The active fibrogenesis marker PRO-C3 was associated with disease progression and liver-related outcomes in patients with CHC, with a 4-fold increased hazard (95% CI: 1.91-8.30) of liver-related outcomes in patients with high compared with low PRO-C3 levels at baseline. Grouping patients with a combination of high or low active fibrogenesis, PRO-C3, and high and low neutrophil activity, CPa9-HNE, revealed that the patient endotype with high fibrogenesis and low neutrophil activity had the highest risk of developing liver-related outcomes in patients with CHC.

CONCLUSIONS: PRO-C3 was associated with the risk of liver-related outcomes in patients with CHC infection in our HALT-C subpopulation. Grouping patients based on neoepitope biomarkers reflecting active fibrogenesis and neutrophil activity could provide fibroinflammatory disease endotype classification that may be applicable to other chronic liver diseases with appropriate validation.