Dynamic changes in the frequency of classical CD14HighCD16- and inflammatory CD14++CD16+ monocyte subsets in patients with advanced liver fibrosis.

UNLABELLED: Hepatitis C is a global health problem, with approximately 71 million individuals chronically infected worldwide. During chronic inflammatory processes, the elevated expression of inflammatory mediators appears to influence the phenotype of circulating monocytes. Our objective was to investigate changes in the phenotypes of peripheral monocyte subsets and the profile of circulating mediators in patients from the Brazilian Amazon during chronic hepatitis C and associated with different degrees of liver fibrosis.

MATERIAL AND

METHODS

This is an observational study involving 30 individuals treated with DAAs and 15 healthy controls, tested for liver function, fibrosis scores (AST/platelet ratio index, FIB-4), percentage of peripheral blood monocyte subsets assessed with based on CD14/CD16 expression. The analysis of soluble immunological biomarkers was performed using the flow cytometry methodology.

RESULTS

Chronic HCV patients showed decreased platelet counts and increased viral load, ALT, AST, alkaline phosphatase in individuals with high fibrosis scores (FIB-4 ≥ F2). Data analysis demonstrated a lower frequency of CD14HighCD16-HLA-DR+ cells, while inflammatory CD14++CD16+HLA-DR+ monocytes increased the expression of CD11a and CD11b integrins, CD49d activation markers, and the inflammatory receptor P2X7. Serum cytokine expression showed that liver fibrosis is associated with higher serum levels of IL-6, CXCL8, and CXCL9 compared to mild liver disease.

CONCLUSIONS

In conclusion, our findings demonstrated that Chronic HCV infection alters the frequency of peripheral inflammatory monocyte subsets, impacting cellular markers and activation in severe liver impairment (FIB-4 ≥ F2). Soluble biomarkers modulate pro-inflammatory monocyte phenotypes, linked to inflammation and fibrosis.