Characterization of the stages of chronic liver disease based on plasma proteins involved in systemic inflammation

Cirrhosis is characterized by progressive fibrosis, portal hypertension, and cirrhosis-associated immune dysfunction, combining systemic inflammation and immunodeficiency. Although systemic inflammation plays a central role in disease progression and complications, current prognostic scores do not incorporate inflammatory biomarkers. This study aimed to characterize stages of chronic liver disease (CLD) according to a panel of plasma proteins involved in systemic inflammation in patients with and without bacterial infection.

Patients with CLD were classified according to clinical stages of cirrhosis and assigned to NON-INFECTION or INFECTION cohort. Baseline characteristics and routine inflammatory parameters such as CRP, IL-6, procalcitonin and MDW were evaluated. Additional plasma biomarkers related with systemic inflammation and fibrosis (S100A8/S100A9, copeptin, CD5L, sCD14, sCD163) were quantified by ELISA.

Eighty-three patients were included in the NON-INFECTION cohort and 21 in the INFECTION cohort. In infection-free patients, CRP, IL-6, procalcitonin, MDW, and sCD163 increased progressively across disease stages, with significant differences between compensated and decompensated cirrhosis. Elevated inflammatory markers were observed even in early stages. Strong correlations (r>0.7) were identified between CRP and IL-6, particularly in advanced stages. In infected patients, CRP, procalcitonin, IL-6, and S100A8/S100A9 decreased significantly after infection resolution. However, inflammatory biomarkers frequently remained above normal ranges despite clinical resolution.

Systemic inflammation biomarkers increase progressively with cirrhosis severity and remain elevated even in the absence of infection, complicating diagnostic interpretation. Selected biomarkers, particularly CRP, IL-6, procalcitonin, and S100A8/S100A9, may help characterize infection-related inflammatory changes in patients with chronic liver disease. However, their clinical utility requires validation in larger independent cohorts.