Dynamic Changes of the Frequency of Classic and Inflammatory Monocytes Subsets and Natural Killer Cells in Chronic Hepatitis C Patients Treated by Direct-Acting Antiviral Agents.

Gang Ning,Ying-Fu Zeng,Yi-Ting Li,Chao-Shuang Lin,You-Ming Chen,Ying Zhang

doi:10.1155/2017/3612403

Abstract

Objective Up to now, little was known about the immunological changes of chronic hepatitis C (CHC) patients treated with direct-acting antiviral agents (DAAs); we try to explore the effect of DAAs on the frequency of monocytes, NK cells, and cytokines that promote their activation. Methods 15 treatment-naive CHC patients and 10 healthy controls were recruited. Patients were examined before DAAs therapy (0 w) and at week 4 (4 w) and week 12 (12 w) of therapy. Percentage of monocytes and NK cells of the peripheral blood was analyzed by flow cytometry. Serum cytokines IL-12, IL-18, CXCL10, CXCL11, sCD14, and sCD163 were measured by enzyme linked immunosorbent assay. Results The frequency of CD3–CD16+CD56+ NK cells and classic CD14++CD16− monocytes decreased, while CD14+CD16+ monocytes and cytokines IL-12, IL-18, CXCL10, CXCL11, sCD14, and sCD163 increased at 0 w compared to healthy controls. During DAAs treatment, the decreased NK cells and classic monocytes gradually increased to normal levels; the increased inflammatory monocytes and cytokines IL-12 and CXCL11 decreased to normal levels, but the increased cytokines IL-18, CXCL10, sCD14, and sCD163 still remained at high levels at 12 w though they decreased rapidly from 0 w. Conclusion Our results showed that DAAs treatment attenuated the activation of monocytes and NK cells in CHC patients. Trial registration number is NCT03063723.

Highlights

Treatment of hepatitis C virus (HCV) infection has greatly advanced with the advent of the new direct-acting antivirals (DAAs) in the past 5 years
We aim to explore the effect of antiviral treatment of chronic hepatitis C (CHC) patients with DAAs on the frequency of monocytes [18], NK cells (CD3−CD16+CD56+) [19], and cytokines IL-12, IL-18, CXCL10, and CXCL11, which are necessary to activation of NK cells, and soluble CD14 and soluble CD163, which reflect monocytes activation
The frequency of classic CD14++CD16− monocytes was less than healthy controls at baseline (0 w) (59.14 ± 0.54% versus 72.75 ± 1.31%, P < 0.001) and gradually increased to HC levels (71.54 ± 2.99% versus 72.75 ± 1.31%, P > 0.05) during DAAs treatment (12 w)

Summary

Introduction

Treatment of hepatitis C virus (HCV) infection has greatly advanced with the advent of the new direct-acting antivirals (DAAs) in the past 5 years. Among all the DAAs regimens, daclatasvir/sofosbuvir and ledipasvir/ sofosbuvir are recommended for all of the genotypes except for patients with genotype 3 infection with cirrhosis by WHO. These two DAAs regimens are included in voluntary licensing agreements signed between the originator companies and generics companies. Daclatasvir/sofosbuvir and ledipasvir/sofosbuvir are already available in generic formulations in some countries. It has been report reported that the price for a 12-week regimen of generic sofosbuvir would be less than US$ 500/patient in India, and no doubt, the wide-scale implementation of HCV treatment will be facilitated by this rapid reduction in the price of daclatasvir/sofosbuvir and ledipasvir/sofosbuvir [4]

Methods

Results

Conclusion