Ishii Koji, Shinohara Mie, Kogame Michio, Shiratori Misato, Higami Katsuya, Kanayama Kaori, Shiozawa Kazue, Wakui Noritaka, Nagai Hidenari, Watanabe Manabu, Sumino Yasukiyo
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Faculty of Medicine, Toho University School of Medicine, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan.
Hepatol Int. 2012 Apr;6(2):468-74. doi: 10.1007/s12072-011-9305-8. Epub 2011 Aug 6.
BACKGROUND/AIM: The number of amino acid (AA) mutations in the interferon sensitivity determining region (ISDR) of NS5A is reported to affect the response to interferon (IFN) therapy in patients with chronic hepatitis C (CHC). The aim of this study was to clarify whether host immunity is influenced by the number of AA mutations in the ISDR.
Subjects included 44 patients with CHC infected with genotype 1b and high viral load. The number of AA mutations in the ISDR was retrospectively determined using stored serum samples taken immediately before starting therapy. All patients received IFN-alpha 2b or pegylated-IFN (PEG-IFN)-alpha 2b and ribavirin. When serum hepatitis C virus-ribonucleic acid (HCV-RNA) was negative at 4 or 12 weeks after starting therapy, the patient was defined as having rapid viral response (RVR) or early viral response (EVR), respectively. CD4(+) T cell (Th1 or Th2) in peripheral blood (PB) before and until day 56 of treatment was analyzed.
Rates of RVR and EVR were 0 (0/21) and 14% (3/21), respectively, in patients with one or fewer AA mutations in the ISDR (ISDR0-1), and 30 (7/23), and 74% (17/23), respectively, with two or more AA mutations in the ISDR (ISDR > 2). Although the percentage of PB Th1 cells did not differ between the two groups during the study period, the percentage of PB Th2 cells was significantly lower in the ISDR0-1 group than in the ISDR > 2 group at baseline and on days 3, 7, 14, and 28 of treatment.
The number of AA mutations in the ISDR influenced PB Th2 cells before and until day 28, and was associated with higher RVR and EVR rates.
背景/目的：据报道，NS5A的干扰素敏感性决定区（ISDR）中的氨基酸（AA）突变数量会影响慢性丙型肝炎（CHC）患者对干扰素（IFN）治疗的反应。本研究的目的是阐明ISDR中的AA突变数量是否会影响宿主免疫力。
研究对象包括44例感染1b型基因型且病毒载量高的CHC患者。使用治疗开始前即刻采集并储存的血清样本，回顾性确定ISDR中的AA突变数量。所有患者均接受α-2b干扰素或聚乙二醇化干扰素（PEG-IFN）-α-2b与利巴韦林治疗。治疗开始后4周或12周时血清丙型肝炎病毒核糖核酸（HCV-RNA）呈阴性的患者，分别被定义为具有快速病毒应答（RVR）或早期病毒应答（EVR）。分析治疗前及治疗至第56天外周血（PB）中的CD4(+) T细胞（Th1或Th2）。
ISDR中AA突变数量为1个或更少（ISDR0-1）的患者，RVR和EVR发生率分别为0（0/21）和14%（3/21）；ISDR中AA突变数量为2个或更多（ISDR > 2）的患者，RVR和EVR发生率分别为30%（7/23）和74%（17/23）。尽管在研究期间两组的PB Th1细胞百分比无差异，但在基线以及治疗第3、7、14和28天，ISDR0-1组的PB Th2细胞百分比显著低于ISDR > 2组。
ISDR中的AA突变数量在治疗前及治疗至第28天影响PB Th2细胞，并与较高的RVR和EVR发生率相关。
