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Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers.
Liver Transpl. 2016 07; 22(7):994-1005.LT

Abstract

Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P < 0.01). In parallel with this, the pH of the bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD.

Authors+Show Affiliations

Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Surgical Research Laboratory, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26946466

Citation

Op den Dries, Sanna, et al. "Normothermic Machine Perfusion Reduces Bile Duct Injury and Improves Biliary Epithelial Function in Rat Donor Livers." Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, vol. 22, no. 7, 2016, pp. 994-1005.
Op den Dries S, Karimian N, Westerkamp AC, et al. Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers. Liver Transpl. 2016;22(7):994-1005.
Op den Dries, S., Karimian, N., Westerkamp, A. C., Sutton, M. E., Kuipers, M., Wiersema-Buist, J., Ottens, P. J., Kuipers, J., Giepmans, B. N., Leuvenink, H. G., Lisman, T., & Porte, R. J. (2016). Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers. Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 22(7), 994-1005. https://doi.org/10.1002/lt.24436
Op den Dries S, et al. Normothermic Machine Perfusion Reduces Bile Duct Injury and Improves Biliary Epithelial Function in Rat Donor Livers. Liver Transpl. 2016;22(7):994-1005. PubMed PMID: 26946466.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers. AU - Op den Dries,Sanna, AU - Karimian,Negin, AU - Westerkamp,Andrie C, AU - Sutton,Michael E, AU - Kuipers,Michiel, AU - Wiersema-Buist,Janneke, AU - Ottens,Petra J, AU - Kuipers,Jeroen, AU - Giepmans,Ben N, AU - Leuvenink,Henri G D, AU - Lisman,Ton, AU - Porte,Robert J, PY - 2015/09/13/received PY - 2016/02/04/revised PY - 2016/02/14/accepted PY - 2016/3/7/entrez PY - 2016/3/8/pubmed PY - 2017/10/17/medline SP - 994 EP - 1005 JF - Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society JO - Liver Transpl VL - 22 IS - 7 N2 - Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P < 0.01). In parallel with this, the pH of the bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD. SN - 1527-6473 UR - https://www.unboundmedicine.com/medline/citation/26946466/Normothermic_machine_perfusion_reduces_bile_duct_injury_and_improves_biliary_epithelial_function_in_rat_donor_livers_ L2 - https://doi.org/10.1002/lt.24436 DB - PRIME DP - Unbound Medicine ER -