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Methylene blue treatment of grafts during cold ischemia time reduces the risk of hepatitis C virus transmission

(2018) JOURNAL OF INFECTIOUS DISEASES. 218(11). p.1711-1721
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Abstract
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.
Keywords
kidney transplantation, HCV-positive organs, methylene blue, viral transmission, KIDNEY-TRANSPLANTATION, INDUCED APOPTOSIS, INACTIVATION, INFECTION, MECHANISMS, DONORS, CELLS, HCV

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Citation

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Chicago
Helfritz, Fabian A, Denisa Bojkova, Verena Wanders, Nina Kuklinski, Sandra Westhaus, Charlotte von Horn, Ursula Rauen, et al. 2018. “Methylene Blue Treatment of Grafts During Cold Ischemia Time Reduces the Risk of Hepatitis C Virus Transmission.” Journal of Infectious Diseases 218 (11): 1711–1721.
APA
Helfritz, F. A., Bojkova, D., Wanders, V., Kuklinski, N., Westhaus, S., von Horn, C., Rauen, U., et al. (2018). Methylene blue treatment of grafts during cold ischemia time reduces the risk of hepatitis C virus transmission. JOURNAL OF INFECTIOUS DISEASES, 218(11), 1711–1721.
Vancouver
1.
Helfritz FA, Bojkova D, Wanders V, Kuklinski N, Westhaus S, von Horn C, et al. Methylene blue treatment of grafts during cold ischemia time reduces the risk of hepatitis C virus transmission. JOURNAL OF INFECTIOUS DISEASES. 2018;218(11):1711–21.
MLA
Helfritz, Fabian A, Denisa Bojkova, Verena Wanders, et al. “Methylene Blue Treatment of Grafts During Cold Ischemia Time Reduces the Risk of Hepatitis C Virus Transmission.” JOURNAL OF INFECTIOUS DISEASES 218.11 (2018): 1711–1721. Print.
@article{8576092,
  abstract     = {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.},
  author       = {Helfritz, Fabian A and Bojkova, Denisa and Wanders, Verena and Kuklinski, Nina and Westhaus, Sandra and von Horn, Charlotte and Rauen, Ursula and Gallinat, Anja and Baba, Hideo A and Skyschally, Andreas and Swoboda, Sandra and Kinast, Volker and Steinmann, Eike and Heusch, Gerd and Minor, Thomas and Meuleman, Philip and Paul, Andreas and Ciesek, Sandra},
  issn         = {0022-1899},
  journal      = {JOURNAL OF INFECTIOUS DISEASES},
  language     = {eng},
  number       = {11},
  pages        = {1711--1721},
  title        = {Methylene blue treatment of grafts during cold ischemia time reduces the risk of hepatitis C virus transmission},
  url          = {http://dx.doi.org/10.1093/infdis/jiy386},
  volume       = {218},
  year         = {2018},
}

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