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巨噬细胞炎性蛋白-1α(MIP-1α)、MIP-1β 和正常 T 细胞表达和分泌的调节激活因子(RANTES)的快速趋化因子反应与慢性丙型肝炎治疗中的持续病毒学应答相关。

A rapid chemokine response of macrophage inflammatory protein (MIP)-1α, MIP-1β and the regulated on activation, normal T expressed and secreted chemokine is associated with a sustained virological response in the treatment of chronic hepatitis C.

机构信息

Laboratory of Gastroenterology and Nutrition, Institute of Clinical Medicine, University of Tromsø, Norway.

出版信息

Clin Microbiol Infect. 2011 Feb;17(2):204-9. doi: 10.1111/j.1469-0691.2010.03206.x.

Abstract

The role of chemokines in chronic hepatitis C virus (HCV) infection is not fully understood. The present study aimed to characterize the baseline serum concentrations and the initial β-chemokine response to treatment with interferon-α and ribavirin with respect to the final clinical outcome of virological response to treatment. Serum concentrations of alanine aminotransferase (ALT) and of the CC subfamily chemokines [macrophage inflammatory protein (MIP)-1α, MIP-1β, monocyte chemoattractant protein (MCP)-1 and the regulated on activation, normal T expressed and secreted (RANTES) chemokine] were measured in patients with chronic HCV infection and in healthy individuals. Necroinflammation and fibrosis were scored in liver biopsies. Treatment outcomes were classified as with or without a sustained virological response after a full-course treatment according to the genotypes. The main treatment group consisted of 72 patients with chronic hepatitis C, whereas 24-h blood samples were available for 42 patients. Increased baseline levels of all CC chemokines were found in the two responder groups compared to the healthy controls, although significant levels were reached only for MIP-1α and MCP-1. No correlation was observed between chemokine levels and serum ALT levels, any histological necroinflammatory parameters, or the fibrosis grade. After 24 h of treatment, increases in MIP-1α, MIP-1β and RANTES levels were exclusively observed in the group with sustained virological response. MCP-1 was also significantly increased after 24 h in both responder groups, although no differences were observed between the two responder groups. In conclusion, an early MIP-1α, MIP-1β, and RANTES response may predict a sustained response to virological treatment.

摘要

趋化因子在慢性丙型肝炎病毒(HCV)感染中的作用尚未完全阐明。本研究旨在描述基线血清浓度以及对干扰素-α和利巴韦林治疗的初始β-趋化因子反应与治疗的最终病毒学应答临床结果之间的关系。在慢性 HCV 感染患者和健康个体中测量了丙氨酸转氨酶(ALT)血清浓度和 CC 亚家族趋化因子[巨噬细胞炎症蛋白(MIP)-1α、MIP-1β、单核细胞趋化蛋白(MCP)-1和调节激活、正常 T 细胞表达和分泌(RANTES)趋化因子]的浓度。在肝活检中对坏死性炎症和纤维化进行评分。根据基因型,将治疗结果分为完全疗程后是否有持续病毒学应答。主要治疗组包括 72 例慢性丙型肝炎患者,其中 42 例有 24 小时的血液样本。与健康对照组相比,两个应答组的所有 CC 趋化因子的基线水平均升高,尽管仅 MIP-1α和 MCP-1 达到显著水平。趋化因子水平与血清 ALT 水平、任何组织学坏死性炎症参数或纤维化等级之间未观察到相关性。治疗 24 小时后,仅在持续病毒学应答组中观察到 MIP-1α、MIP-1β 和 RANTES 水平的增加。在两个应答组中,MCP-1 在治疗 24 小时后也显著增加,但两组之间无差异。总之,早期 MIP-1α、MIP-1β 和 RANTES 反应可能预测对病毒学治疗的持续应答。

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