Yap P L
Edinburgh & S.E. Scotland Blood Transfusion Service, UK.
Clin Exp Immunol. 1996 May;104 Suppl 1:35-42.
The viral safety of intravenous immune globulin (IVIG) preparations has been investigated since 1983 when it was discovered that non-A, non-B hepatitis (NANBH) could be transmitted by an experimental IVIG preparation. Recently, it has been demonstrated that the virus causing NANBH is the hepatitis C virus (HCV). A number of subsequent episodes of HCV transmission by IVIG have been reported, but not all the factors that have led to this transmission are clearly understood. However, based on two episodes of HCV transmission by anti-D immune globulin (formulated for intravenous administration), it appears that cold ethanol fractionation is important in ensuring viral safety because both of the implicated anti-D immune globulin preparations were manufactured without cold ethanol fractionation. Other HCV transmission episodes have been associated with chromatography (particularly DEAE-Sephadex chromatography) as a separation step carried out to further purify IgG, after cold ethanol fractionation, and it is possible that such a procedure has only a marginal partitioning capacity for infective HCV virions. The role of anti-HCV screening in improving the viral safety of IVIG preparations remains unclear, but a recent transmission episode by a previously safe IVIG preparation suggests that the absence of anti-HCV antibodies during plasma fractionation may affect the partitioning characteristics of HCV and may also cause a loss of neutralizing antibody against HCV. All of the IVIG preparations associated with HCV transmission have been formulated as freeze-dried preparations and this may have been important in stabilizing HCV during the period prior to administration to patients. No other viruses appear to have been transmitted by IVIG preparations, but prior to seroconversion, HCV-infected plasma donors may continue to contaminate plasma pools used for the manufacture of blood products, despite anti-HCV screening, and additional viral inactivation steps such as incubation at pH4 or solvent-detergent treatment should be incorporated into the production process of all IVIG preparations.
自1983年发现非甲非乙型肝炎（NANBH）可通过一种实验性静脉注射免疫球蛋白（IVIG）制剂传播以来，人们一直在研究IVIG制剂的病毒安全性。最近，已证实导致NANBH的病毒是丙型肝炎病毒（HCV）。已有多起关于IVIG传播HCV的报道，但导致这种传播的所有因素尚未完全明确。然而，基于两起抗-D免疫球蛋白（静脉注射用）传播HCV的事件，似乎冷乙醇分级分离对于确保病毒安全性很重要，因为这两起涉及的抗-D免疫球蛋白制剂均未经过冷乙醇分级分离生产。其他HCV传播事件与作为分离步骤的色谱法（特别是二乙氨基乙基葡聚糖凝胶色谱法）有关，该步骤是在冷乙醇分级分离后用于进一步纯化IgG，并且这种方法对传染性HCV病毒粒子的分配能力可能很有限。抗-HCV筛查在提高IVIG制剂病毒安全性方面的作用仍不明确，但最近一次由先前安全的IVIG制剂引发的传播事件表明，血浆分级分离过程中缺乏抗-HCV抗体可能会影响HCV的分配特性，也可能导致针对HCV的中和抗体丧失。所有与HCV传播相关的IVIG制剂均制成冻干制剂，这在将HCV稳定至给患者用药前的这段时间可能很重要。似乎没有其他病毒通过IVIG制剂传播，但在血清转化之前，尽管进行了抗-HCV筛查，受HCV感染的血浆捐献者仍可能继续污染用于生产血液制品的血浆库，所有IVIG制剂的生产过程都应加入额外的病毒灭活步骤，如在pH4条件下孵育或溶剂-去污剂处理。
