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索磷布韦诱导慢性丙型肝炎病毒清除后炎症介质平衡的恢复。

Restoring Inflammatory Mediator Balance after Sofosbuvir-Induced Viral Clearance in Patients with Chronic Hepatitis C.

机构信息

Laboratório Multiusuário de Apoio à Pesquisa em Nefrologia e Ciências Médicas, Faculdade de Medicina, Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niterói, Brazil.

Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Mediators Inflamm. 2018 May 27;2018:8578051. doi: 10.1155/2018/8578051. eCollection 2018.

Abstract

This study aimed at analyzing circulating levels of inflammatory and profibrogenic cytokines in patients with hepatitis C virus (HCV) chronic infection undergoing therapy with direct-acting antiviral agents (DAA) and correlating these immune biomarkers with liver disease status. We studied 88 Brazilian monoinfected chronic hepatitis C patients receiving interferon- (IFN-) free sofosbuvir-based regimens for 12 or 24 weeks, followed-up before therapy initiation and three months after the end of treatment. Liver disease was determined by transient elastography, in addition to APRI and FIB-4 indexes. Analysis of 30 immune mediators was carried out by multiplex or enzymatic immunoassays. Sustained virological response rate was 98.9%. Serum levels of cytokines were increased in HCV-infected patients when compared to control group. CCL-2, CCL-3, CCL-4, CXCL-8, CXCL-10, IL-1, IL-15, IFN-, IL-4, IL-10, TGF-, FGFb, and PAI-1 decreased significantly after antiviral therapy, reaching values similar to noninfected controls. TGF- and suPAR levels were associated with fibrosis/cirrhosis. Also, we observed amelioration in hepatic parameters after DAA treatment. Together, our results suggest that viral control induced by IFN-free DAA therapy restores inflammatory mediators in association with improvement in liver function.

摘要

本研究旨在分析丙型肝炎病毒 (HCV) 慢性感染患者接受直接作用抗病毒药物 (DAA) 治疗时循环中炎症和纤维生成细胞因子的水平,并将这些免疫生物标志物与肝病状况相关联。我们研究了 88 名接受无干扰素 (IFN) 的索磷布韦为基础的方案治疗 12 或 24 周的巴西单感染慢性丙型肝炎患者,在治疗前和治疗结束后三个月进行随访。通过瞬时弹性成像以及 APRI 和 FIB-4 指数来确定肝病。通过多重或酶免疫分析对 30 种免疫介质进行分析。持续病毒学应答率为 98.9%。与对照组相比,HCV 感染患者的血清细胞因子水平升高。抗病毒治疗后,CCL-2、CCL-3、CCL-4、CXCL-8、CXCL-10、IL-1、IL-15、IFN-γ、IL-4、IL-10、TGF-β、FGFb 和 PAI-1 显著降低,达到与未感染对照相似的水平。TGF-β和 suPAR 水平与纤维化/肝硬化相关。此外,我们还观察到 DAA 治疗后肝参数的改善。综上所述,我们的结果表明,无干扰素 DAA 治疗诱导的病毒控制与肝功能改善相关联,可恢复炎症介质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfd7/5994301/76a96504cb98/MI2018-8578051.001.jpg

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