Molecular Quantification of Fibrogenesis and Macrophage Activation Associate With Clinical Worsening in Patients With Cirrhosis

Knowledge of the potential of biomarkers for monitoring clinical improvement, assessing trajectory or disease progression in advanced chronic liver disease is still insufficient. This study investigated biomarkers of fibrosis and macrophage activation over time in newly diagnosed patients with cirrhosis and their potential association with hospital admissions. Biomarkers were measured in plasma from 74 patients with cirrhosis and portal hypertension. The biomarkers included the fibrogenesis marker nordicPRO‐C3, the endotrophin marker nordicPRO‐C6 and the macrophage activation markers nordicVICM, sCD163 and sCD206. Samples and clinical data were collected at baseline and at 3 and 6 months after. Patients with high PRO‐C6 levels (above Q3) at baseline had a 2.4‐fold higher risk of hospital admissions (HR = 2.43, 95% CI: 1.04–5.70, p < 0.05), and above sCD163 Q3 levels had a 2.4‐fold higher risk (HR = 2.40, 95% CI: 1.02–5.62, p < 0.05) compared to patients with low levels (below Q3). Following enrollment, PRO‐C3 and PRO‐C6 concentrations decreased from baseline to 3 months ( p < 0.05), and PRO‐C6 decreased from 3 months to 6 months ( p < 0.01). VICM and sCD206 decreased from baseline to 6 months ( p < 0.05), and VICM decreased from 3 months to 6 months after enrollment ( p < 0.05). There was no change in sCD163 levels. The fibroblast activity marker PRO‐C6 and the macrophage activation marker sCD163 are associated with the rate of hospital admissions in cirrhosis and portal hypertension. The fibrogenesis markers, PRO‐C3 and PRO‐C6, and the macrophage activity markers, VICM and sCD206, all decreased following diagnosis and enrollment. These markers may provide knowledge on the trajectory in patients with cirrhosis.