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（HCV）颗粒按其密度可分为两个组分，即重组分和轻组分。前者与结合免疫球蛋白一起存在。我们已经报道了更高的轻组分和重组分的比例对应于对干扰素治疗的更好的应答率。结果表明，去除免疫球蛋白结合部分可能有助于更好地对干扰素治疗的反应。不仅在慢性丙型肝炎患者的血清中，但在肝组织中的HCV的存在状态进行了研究。肝内存在不同种类的HCV，且准种随肝病的加重而增多，似乎肝是一个分隔区。这些结果有助于理解HCV病毒学和本血浆置换研究的生理学。因此，我们制作了几种用于血浆置换的柱，以去除慢性丙型肝炎患者血清中的免疫球蛋白。通过批试验和微型柱装置研究了适宜流速和柱体积下的血浆吸附速率，筛选出最佳柱试剂，并在动物实验室用最佳柱试剂对2只感染HCV的黑猩猩进行了血浆分离。手术在循环、呼吸、肾功能方面安全完成。生化变化是短暂的，手术后没有感染。但由于使用了抗凝剂，导致置管部位出血，血清和肝组织中HCV含量发生了一系列变化。

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.