Removal of Hepatitis C Virus in the Serum of Chimpanzees by Phasmapheresis

丙型肝炎患者血清中的丙型肝炎病毒颗粒按密度、重组分和轻组分可分为两个组分。前者以结合免疫球蛋白的形式存在。我们已经报道，轻组分和重组分的比例越高，对干扰素治疗的应答率就越高。结果表明，去除免疫球蛋白结合部分有助于更好地对抗干扰素治疗。不仅研究了慢性丙型肝炎患者血清中丙型肝炎病毒的现状，而且研究了肝组织中丙型肝炎病毒的现状。在肝脏中存在不同种类的丙型肝炎病毒，且准种丙型肝炎病毒的数量随着肝病的严重程度而增加，就好像肝脏是由一个隔室组成的。这些结果有助于了解丙型肝炎病毒的病毒学和生理学研究。因此，我们制作了几个专栏，用于血浆置换去除慢性丙型肝炎患者血清中的免疫球蛋白。通过批量实验和微型柱状仪考察了不同流动相和柱子体积对丙型肝炎病毒的吸收率，筛选出了最佳的柱状物。手术在循环、呼吸、肾功能等方面均安全完成。生化改变是一过性的，术后无感染。然而，由于使用了抗凝剂，导尿管部位出现出血。黑猩猩的血清和肝组织中出现了一系列的丙型肝炎病毒变化。

Hepatitis C virus (HCV) particles in the serum of hepatitis C patients can be separated into the two fractions according to their density, heavy fraction and light fraction. The former is present with the binding immunoglobulin. We have reported that a higher ratio of the light and the heavy fractions corresponds to the better response rate against interferon therapy. The results indicate that removal of the immunoglobulin-binding fraction may help better response against interferon therapy.Not only present status of HCV in the serum of chronic hepatitis C patients, but in the liver tissues were studied. Different species of HCV were present in the liver, and the quasispecies of HCV was increased with the severity of liver disease as if the liver consits of a compartment. These results are helpful for the understanding of HCV virology and physiology of this plasma-pheresis study.Thus, we made several columns for the usage of plasmapheresis which remove immunoglobulin in the serum of chronic hepatitis C patients. The absorption rate with appropriate flow and column volumes was studied by a batch test and a mini-column apparatus, and the best column reagents was chosen.Two chimpanzees infected with HCV were plasmapheresed using the best reagents in an animal facility. The procedure was finished with safe in terms of circulation, respiration, renal function. Biochemical changes were transient, and there were no infection after the procedure. However, due to anticoagulant used, bleeding at the site of catheterization was found. Serial changes of HCV in the serum and liver tissue were demonstrated in the chimpanzees.