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Successful DAA therapy for chronic hepatitis C reduces HLA-DR on monocytes and circulating immune mediators: a long-term follow-up study.
Immunology Letters ( IF 3.3 ) Pub Date : 2020-09-15 , DOI: 10.1016/j.imlet.2020.09.002
Natalia Fonseca Rosário 1 , Geórgia do Nascimento Saraiva 1 , Thalia Medeiros 1 , Mariana Gandini 2 , Gilmar Lacerda 3 , Paulo Emílio Corrêa Leite 4 , Thaís Guaraná Andrade 5 , Elzinandes Leal Azeredo 6 , Analúcia Rampazzo Xavier 3 , Andrea Alice Silva 3
Affiliation  

Introduction

After DAA treatment for chronic hepatitis C infection, peripheral monocyte subsets from patients who achieved sustained virological response (SVR) reduced compared to healthy control. Improvement in inflammatory parameters and liver stiffness has been observed. However, little is known about the long-term impact of DAA treatment on peripheral monocyte subsets and immune mediators levels.

Objectives

We aimed to examine peripheral monocyte subsets and immune mediators levels in Brazilian chronic HCV patients after long-term successful IFN-free SOF-based treatment.

Material and methods

We analyzed CD14++CD16-, CD14++CD16+ and CD14+CD16++ monocytes and 27 immune mediators by flow cytometry and analysis of multiple secreted proteins assay, respectively, in monoinfected chronic HCV patients receiving IFN-free sofosbuvir-based regimens followed before treatment, at SVR and one year after the end of treatment (1y).

Results

Twenty-one biomarkers decreased significantly at 1y and 55–80 % of patients this reduction at 1y. Experimented patients presented a greater modulation of immune mediators at 1y. HLA-DR expression significantly decreased on CD14++CD16- and CD14++CD16+ monocytes at 1y when compared to SVR.

Conclusions

Successful DAA therapy did not modify monocyte subsets frequency but reduced monocyte activation at 1y and sustained the downregulation and restoration of circulating immune mediators, indicating that long-term reversal of inflammation status could occur after HCV eradication.



中文翻译:

慢性丙型肝炎的成功 DAA 治疗可减少单核细胞和循环免疫介质上的 HLA-DR:一项长期随访研究。

介绍

在对慢性丙型肝炎感染进行 DAA 治疗后,与健康对照相比,获得持续病毒学应答 (SVR) 的患者的外周单核细胞亚群减少。已观察到炎症参数和肝脏硬度的改善。然而,关于 DAA 治疗对外周单核细胞亚群和免疫介质水平的长期影响知之甚少。

目标

我们旨在检查长期成功的无干扰素 SOF 治疗后巴西慢性 HCV 患者的外周单核细胞亚群和免疫介质水平。

材料与方法

我们分别通过流式细胞术和多种分泌蛋白分析分析了 CD14++CD16-、CD14++CD16+ 和 CD14+CD16++ 单核细胞和 27 种免疫介质,在治疗前接受无干扰素的基于索非布韦的方案的单一感染慢性 HCV 患者中, 在 SVR 和治疗结束后一年 (1y)。

结果

21 种生物标志物在第 1 年显着下降,55-80% 的患者在第 1 年下降。实验患者在 1 年时表现出更大的免疫介质调节。与 SVR 相比,CD14++CD16- 和 CD14++CD16+ 单核细胞上的 HLA-DR 表达在 1 年时显着降低。

结论

成功的 DAA 治疗不会改变单核细胞亚群频率,但会在 1 年时降低单核细胞活化并持续下调和恢复循环免疫介质,表明在根除 HCV 后炎症状态可能发生长期逆转。

更新日期:2020-09-30
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