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三种不同方案干扰素治疗慢性丙型肝炎早期的抗病毒作用及病毒动力学:干扰素-β每日两次给药与干扰素-α联合利巴韦林联合治疗之间的差异

Anti-viral actions and viral dynamics in the early phase of three different regimens of interferon treatment for chronic hepatitis C: differences between the twice-daily administration of interferon-beta treatment and the combination therapy with interferon-alpha plus ribavirin.

作者信息

Nakajima Hirofumi, Shimomura Hiroyuki, Iwasaki Yoshiaki, Ikeda Fusao, Umeoka Fumi, Chengyu Piao, Taniguchi Hideaki, Ohnishi Yasuhiro, Takagi Shin-jirou, Fujioka Shin-ichi, Shiratori Yasushi

机构信息

Department of Medicine and Medical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.

出版信息

Acta Med Okayama. 2003 Oct;57(5):217-25. doi: 10.18926/AMO/32825.

Abstract

To improve the efficacy of interferon (IFN) treatment for chronic hepatitis C, we have proposed the twice-daily administration of IFN-beta as a promising induction therapy. In this study, we demonstrated differences between the clearance of circulating HCV-RNA and the induction of anti-viral actions during the first 2 weeks of treatment. Nine patients with a high viral load and genotype 1b were randomly assigned to 3 groups: group A received 3MU of IFN-beta twice a day at intervals of 5 and 19 h; group B received 3MU of IFN-beta twice a day at intervals of 10 and 14 h; group C received 6MU of IFN-alpha once a day with ribavirin. The expression of OAS2, PKR, and MxA in peripheral blood mononuclear cells (PBMCs) were quantified by real-time polymerase chain reaction method. The viral clearance showed a bi-phasic pattern, and those in the second phase of groups A and B were significantly steeper than that of group C. The peak level of OAS2 during the first phase was correlated with the first phase decay. The MxA expression tended to be higher in group A and B than in group C. The expression of these 3 proteins tended to decrease at day 6 in group C, but increase in groups A and B. These might make differences in the viral decay during the second phase

摘要

为提高干扰素(IFN)治疗慢性丙型肝炎的疗效,我们提出将β-干扰素每日两次给药作为一种有前景的诱导疗法。在本研究中,我们证明了治疗前2周循环HCV-RNA清除率和抗病毒作用诱导之间的差异。9例高病毒载量且基因型为1b的患者被随机分为3组:A组每隔5小时和19小时接受3MUβ-干扰素,每日两次;B组每隔10小时和14小时接受3MUβ-干扰素,每日两次;C组每天接受6MUα-干扰素联合利巴韦林治疗。采用实时聚合酶链反应法定量外周血单个核细胞(PBMC)中OAS2、PKR和MxA的表达。病毒清除呈现双相模式,A组和B组第二阶段的清除率明显比C组更陡。第一阶段OAS2的峰值水平与第一阶段的衰减相关。A组和B组的MxA表达倾向于高于C组。这3种蛋白的表达在C组第6天时趋于下降,但在A组和B组中升高。这些可能导致第二阶段病毒衰减的差异

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