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血浆白介素-6 和白介素-9 可预测 HIV/HCV 合并感染患者干扰素-α联合利巴韦林治疗的失败。

Plasma IL-6 and IL-9 predict the failure of interferon-α plus ribavirin therapy in HIV/HCV-coinfected patients.

机构信息

Laboratorio de Epidemiología Molecular de Enfermedades Infecciosas, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.

出版信息

J Antimicrob Chemother. 2012 May;67(5):1238-45. doi: 10.1093/jac/dkr595. Epub 2012 Jan 31.

DOI:10.1093/jac/dkr595
PMID:22294644
Abstract

BACKGROUND

The cytokine profile plays an important role in treatment outcome of hepatitis C virus (HCV) infection, and probably modulates the immune response against HCV. The aim of this study was to evaluate which cytokines affect the response to interferon-α (IFN-α) and ribavirin therapy and how these cytokines change 72 weeks after starting anti-HCV therapy in HIV/HCV-coinfected patients.

METHODS

We carried out a retrospective follow-up study of 65 patients on anti-HCV therapy. A sustained virological response (SVR) was defined as an undetectable HCV viral load up to 24 weeks after the end of treatment. Cytokines were measured using a multiplex immunoassay kit.

RESULTS

On starting anti-HCV therapy, non-responder (NR) patients had higher levels of interleukin (IL)-6, IL-9, IL-10 and tumour necrosis factor (TNF)-α (P < 0.05), while IL-17A levels were increased in SVR patients (P = 0.058). However, only patients with high levels of IL-6 and IL-9 had decreased odds to achieve SVR (P < 0.05). Plasma levels of IL-6 and IL-9 had a high predictive value for SVR failure [area under the ROC curve (AUC) 0.839 (95% CI 0.733-0.945) and AUC 0.769 (95% CI 0.653-0.884)]. In addition, during anti-HCV therapy, IL-1β showed an increase in NR patients (P = 0.015) and IL-10 decreased in SVR patients (P = 0.049). After clearing HCV infection, low levels of TNF-α, IL-6, IL-9, IL-10, IL-13 and IL-22 were found in SVR patients (P < 0.05), as well as IL-1β, but only near statistical significance (P = 0.073).

CONCLUSIONS

High plasma levels of IL-6 and IL-9 had a high predictive value for SVR failure. Furthermore, clearing of HCV infection was associated with low inflammatory and T helper (Th)2/Th9/Th22 cytokine levels.

摘要

背景

细胞因子谱在丙型肝炎病毒 (HCV) 感染的治疗结果中发挥重要作用,并可能调节针对 HCV 的免疫反应。本研究旨在评估哪些细胞因子影响干扰素-α (IFN-α) 和利巴韦林治疗的反应,以及在 HIV/HCV 合并感染患者开始抗 HCV 治疗 72 周后这些细胞因子如何变化。

方法

我们对 65 例接受抗 HCV 治疗的患者进行了回顾性随访研究。持续病毒学应答 (SVR) 定义为治疗结束后 24 周内无法检测到 HCV 病毒载量。使用多重免疫测定试剂盒测量细胞因子。

结果

在开始抗 HCV 治疗时,无应答 (NR) 患者的白细胞介素 (IL)-6、IL-9、IL-10 和肿瘤坏死因子 (TNF)-α 水平较高 (P<0.05),而 SVR 患者的 IL-17A 水平升高 (P=0.058)。然而,只有高水平的 IL-6 和 IL-9 的患者获得 SVR 的几率降低 (P<0.05)。IL-6 和 IL-9 的血浆水平对 SVR 失败具有很高的预测价值[ROC 曲线下面积 (AUC) 0.839(95%CI 0.733-0.945)和 AUC 0.769(95%CI 0.653-0.884)]。此外,在抗 HCV 治疗期间,NR 患者的 IL-1β 增加 (P=0.015),而 SVR 患者的 IL-10 减少 (P=0.049)。清除 HCV 感染后,SVR 患者的 TNF-α、IL-6、IL-9、IL-10、IL-13 和 IL-22 水平较低 (P<0.05),IL-1β 也较低,但仅接近统计学意义 (P=0.073)。

结论

高血浆水平的 IL-6 和 IL-9 对 SVR 失败具有很高的预测价值。此外,清除 HCV 感染与低炎症和辅助性 T (Th)2/Th9/Th22 细胞因子水平相关。

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