Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Daclatasvir and Sofosbuvir Therapy Enhance Monocyte Phenotypic Changes in Naive Chronic Hepatitis C Patients: A Prospective Cohort Study.

Abstract

Background: Liver inflammation influences monocyte function, recruitment, and consequently inflammatory and fibrogenic responses. We aimed to investigate changes in the circulating monocyte phenotypes in response to Daclatasvir-Sofosbuvir (SOF/DCV) therapy in chronic hepatitis C (CHC) and relate findings to the viral kinetics and the fibrosis score. Methods: A longitudinal study involving 100 treatment-naïve patients and 30 healthy controls, tested for liver function, fibrosis scores (AST to platelet ratio index, FIB-4), and blood monocyte subsets based on CD14/CD16 expression by flow cytometer. Results: CHC patients had significantly lower albumin, higher ALT, AST, alkaline phosphatase, and increased fibrosis scores [Fib-4 (1.85±0.98) and AST to platelet ratio index (APRI) (0.6±0.35)], higher monocyte and eosinophil counts and lowered neutrophil to monocyte ratio (NMR), and lymphocyte to monocyte ratio (LMR) compared to week 12 and control. CHC patients had significantly increased median [classical (52.2% versus 25.8%, P=0.004) and inflammatory CD16+ monocytes (23.1% versus 13.58%, P=0.035)]. Therapy results in achievement of sustained virological response in 92% of cases, liver function improvement, and normalization of the inflammatory monocytes subsets. Monocyte counts showed positive correlation with viral load, calculated fibrosis scores (APRI and FIB-4 score), AST, ALT, ANC, and inverse correlations with serum albumin, leukocyte, eosinophil, NMR, and LMR. Multivariate regression found eosinophil count as predictors of CD16+ monocyte count in CHC patients. Conclusion: CHC infection promotes a proinflammatory and profibrotic monocytes profile. SOF/DCV therapy efficiently decreases viral load, reduces fibrosis potentials, attenuates monocyte activation, normalizes monocytes phenotypic abnormalities, and modulates monocyte subsets recruitment and differentiation later in the liver.