Itose Ichiyo, Kanto Tatsuya, Inoue Michiyo, Miyazaki Masanori, Miyatake Hideki, Sakakibara Mitsuru, Yakushijin Takayuki, Oze Tsugiko, Hiramatsu Naoki, Takehara Tetsuo, Kasahara Akinori, Katayama Kazuhiro, Kato Michio, Hayashi Norio
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Japan.
J Med Virol. 2007 May;79(5):511-21. doi: 10.1002/jmv.20809.
A combination of pegylated interferon alpha (PEG-IFNalpha) and ribavirin has been used widely. Enhancement of immune response against hepatitis C virus (HCV) is known to be involved in the efficacy of the combination therapy. The aim of the study was to elucidate whether the frequency or function of immunocompetent blood cells is related to the outcome of the therapy. Twenty-five chronic hepatitis C patients with high viral load of HCV genotype 1 who underwent 48 weeks of PEG-IFNalpha2b and ribavirin therapy were examined. During the treatment, frequencies of dendritic cell subsets, helper T cell subsets, and NK cells were phenotypically determined. In some patients, the ability of dendritic cells to stimulate allogeneic CD4(+)T cells was examined at the end and after the therapy. Among the 25 patients, 11 showed a sustained virological response, 11 a transient response, and 3 no response. In comparison with sustained virological responders, non-sustained virological responders showed impaired dendritic cell function at the end and after the treatment. The transient responders showed a decline of plasmacytoid dendritic cell frequency from Weeks 1-12 and impaired dendritic cell function as well. Even in patients who attained negative serum HCV RNA at Week 12, the transient responders showed a significant decrease of plasmacytoid dendritic cell frequency and impaired dendritic cell function. In conclusion, in PEG-IFNalpha and ribavirin combination therapy for chronic hepatitis C patients, the early-phase plasmacytoid dendritic cell frequency and/or end-of-treatment dendritic cell function are related to the virological outcome of the therapy.
聚乙二醇化干扰素α（PEG-IFNα）和利巴韦林的联合疗法已被广泛应用。已知增强针对丙型肝炎病毒（HCV）的免疫反应与联合疗法的疗效有关。本研究的目的是阐明免疫活性血细胞的频率或功能是否与治疗结果相关。对25例HCV基因型1病毒载量高的慢性丙型肝炎患者进行了48周的PEG-IFNα2b和利巴韦林治疗并进行了检查。在治疗期间，通过表型分析确定树突状细胞亚群、辅助性T细胞亚群和自然杀伤细胞的频率。在一些患者中，在治疗结束时和治疗后检查了树突状细胞刺激同种异体CD4(+)T细胞的能力。在这25例患者中，11例显示持续病毒学应答，11例显示短暂应答，3例无应答。与持续病毒学应答者相比，非持续病毒学应答者在治疗结束时和治疗后树突状细胞功能受损。短暂应答者在第1至12周浆细胞样树突状细胞频率下降，树突状细胞功能也受损。即使在第12周血清HCV RNA转阴的患者中，短暂应答者也显示浆细胞样树突状细胞频率显著下降，树突状细胞功能受损。总之，在PEG-IFNα和利巴韦林联合治疗慢性丙型肝炎患者中，早期浆细胞样树突状细胞频率和/或治疗结束时树突状细胞功能与治疗的病毒学结果相关。
