Methylene Blue Treatment of Grafts During Cold Ischemia Time Reduces the Risk of Hepatitis C Virus Transmission
Methylene Blue Treatment of Grafts During Cold Ischemia Time Reduces the Risk of Hepatitis C Virus Transmission
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DOI：
10.1093/infdis/jiy386
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发表时间：
2018-12-01
影响因子：
6.4
通讯作者：
Ciesek, Sandra
中科院分区：
文献类型：
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作者：
Helfritz, Fabian A.;Bojkova, Denisa;Ciesek, Sandra
背景资料。虽然器官短缺是一个日益严重的问题，但来自丙型肝炎病毒(丙型肝炎病毒)核糖核酸(RNA)阳性捐赠者的器官并不会常规地移植到丙型肝炎病毒阴性的人身上。由于丙型肝炎病毒只感染肝细胞，其他器官，如肾脏，只是通过血液感染丙型肝炎病毒。在这项研究中，我们建立了一个在冷缺血期间减少丙型肝炎病毒粒子的方案。用标准病毒学方法研究了包括亚甲蓝(MB)在内的抗病毒药物在不同保存液中的效果。小型猪的肾脏被Jc1或HCVRNA阳性的人血清污染。之后，用甲基溴冲洗器官。采用低温机灌流优化丙型肝炎病毒减灭率。研究了三种不同的抗病毒药物在体外灭活丙型肝炎病毒的能力。在所有灌注液中，只有MB能完全灭活丙型肝炎病毒。对感染丙型肝炎病毒的小型猪肾脏进行亚甲基亚甲基蓝和低温机灌流处理，对移植肾无不良影响。人肝-uPA-SCID小鼠从这些肾脏流出后，接种后没有建立丙型肝炎病毒感染。这项概念验证研究是减少传染性丙型肝炎病毒颗粒在移植环境中传播的第一步，并可能作为其他相关病原体的模型。
Background. Although organ shortage is a rising problem, organs from hepatitis C virus (HCV) ribonucleic acid (RNA)-positive donors are not routinely transplanted in HCV-negative individuals. Because HCV only infects hepatocytes, other organs such as kidneys are merely contaminated with HCV via the blood. In this study, we established a protocol to reduce HCV virions during the cold ischemic time.Methods. Standard virological assays were used to investigate the effect of antivirals, including methylene blue (MB), in different preservation solutions. Kidneys from mini pigs were contaminated with Jc1 or HCV RNA-positive human serum. Afterwards, organs were flushed with MB. Hypothermic machine perfusion was used to optimize reduction of HCV.Results. Three different antivirals were investigated for their ability to inactivate HCV in vitro. Only MB completely inactivated HCV in the presence of all perfusion solutions. Hepatitis C virus-contaminated kidneys from mini pigs were treated with MB and hypothermic machine perfusion without any negative effect on the graft. Human liver-uPA-SCID mice did not establish HCV infection after inoculation with flow through from these kidneys.Conclusions. This proof-of-concept study is a first step to reduce transmission of infectious HCV particles in the transplant setting and might serve as a model for other relevant pathogens.