Development of a Leukocyte Removal Filter for Hepatitis C Therapy and the Possibility of Multipurpose Treatment

Y. Fueda, H. Kotera
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Abstract

Hepatitis C virus infects and causes inflammation in extrahepatic organs and the liver. Patients with chronic hepatitis C disease receive interferon-based treatment, and both interferon and interferon-free therapies are expensive. We attempted to eliminate hepatitis C virus-infected cells using extracorporeal circulation with a unique filter. We created two types of the filters with syndiotactic polystyrene (SPS) resin sheets in a solution that dissolved hydroxypropyl cellulose (HPC) and cellulose acetate (CA) in oleyl alcohol, respectively. First, hepatitis C virus-positive cells were confirmed in the blood and mononuclear cells of hepatitis C virus-infected volunteers, showing that mononuclear cells phagocytosed the hepatitis C virus. Next, we extracted blood from three healthy volunteers and examined the blood cell removal rate using various filters. The HPC-SPS (fiber diameter, 3.5 μm) showed the highest mononuclear cell removal rate and the lowest platelet removal rate. HPC-SPS reduced hepatitis C virus-positive cells in patients with the hepatitis C virus, and the removal rate of monocytes containing the hepatitis C virus was 77.2%. Thus, HPC-SPS may serve as filter to remove mononuclear cells and granulocytes from blood. Although a technique using extracorporeal circulation is required to apply HPC-SPS, the technical cost is lower than IFN-free drug therapy. We believe that HPC-SPS can be utilized for the treatment of HCV- and leukocyte-related diseases.
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用于丙型肝炎治疗的白细胞去除过滤器的研制及多用途治疗的可能性
丙型肝炎病毒感染肝外器官和肝脏并引起炎症。慢性丙型肝炎患者接受干扰素治疗,干扰素和无干扰素治疗都很昂贵。我们尝试用一种独特的过滤器体外循环消除丙型肝炎病毒感染的细胞。我们分别在溶解羟丙基纤维素(HPC)和醋酸纤维素(CA)的油醇溶液中制备了两种类型的过滤器,其中syndiotactic polystyrene (SPS)树脂片。首先,在丙型肝炎病毒感染志愿者的血液和单核细胞中确认了丙型肝炎病毒阳性细胞,表明单核细胞吞噬了丙型肝炎病毒。接下来,我们从三位健康志愿者身上提取血液,并使用各种过滤器检查血细胞去除率。HPC-SPS(纤维直径为3.5 μm)的单核细胞去除率最高,血小板去除率最低。HPC-SPS降低了丙型肝炎病毒患者体内的丙型肝炎病毒阳性细胞,对含有丙型肝炎病毒的单核细胞的去除率为77.2%。因此,HPC-SPS可作为滤除血液中的单核细胞和粒细胞的过滤器。虽然应用HPC-SPS需要使用体外循环技术,但技术成本低于不含ifn的药物治疗。我们相信HPC-SPS可用于治疗HCV和白细胞相关疾病。
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