Long-term Normothermic Machine Preservation of Partial Livers: First Experience With 21 Human Hemi-livers.
Journal
Annals of surgery
ISSN: 1528-1140
Titre abrégé: Ann Surg
Pays: United States
ID NLM: 0372354
Informations de publication
Date de publication:
01 11 2021
01 11 2021
Historique:
pubmed:
3
8
2021
medline:
23
11
2021
entrez:
2
8
2021
Statut:
ppublish
Résumé
The aim of this study was to maintain long-term full function and viability of partial livers perfused ex situ for sufficient duration to enable ex situ treatment, repair, and regeneration. Organ shortage remains the single most important factor limiting the success of transplantation. Autotransplantation in patients with nonresectable liver tumors is rarely feasible due to insufficient tumor-free remnant tissue. This limitation could be solved by the availability of long-term preservation of partial livers that enables functional regeneration and subsequent transplantation. Partial swine livers were perfused with autologous blood after being procured from healthy pigs following 70% in-vivo resection, leaving only the right lateral lobe. Partial human livers were recovered from patients undergoing anatomic right or left hepatectomies and perfused with a blood based perfusate together with various medical additives. Assessment of physiologic function during perfusion was based on markers of hepatocyte, cholangiocyte, vascular and immune compartments, as well as histology. Following the development phase with partial swine livers, 21 partial human livers (14 right and 7 left hemi-livers) were perfused, eventually reaching the targeted perfusion duration of 1 week with the final protocol. These partial livers disclosed a stable perfusion with normal hepatic function including bile production (5-10 mL/h), lactate clearance, and maintenance of energy exhibited by normal of adenosine triphosphate (ATP) and glycogen levels, and preserved liver architecture for up to 1 week. This pioneering research presents the inaugural evidence for long-term machine perfusion of partial livers and provides a pathway for innovative and relevant clinical applications to increase the availability of organs and provide novel approaches in hepatic oncology.
Sections du résumé
OBJECTIVE
The aim of this study was to maintain long-term full function and viability of partial livers perfused ex situ for sufficient duration to enable ex situ treatment, repair, and regeneration.
BACKGROUND
Organ shortage remains the single most important factor limiting the success of transplantation. Autotransplantation in patients with nonresectable liver tumors is rarely feasible due to insufficient tumor-free remnant tissue. This limitation could be solved by the availability of long-term preservation of partial livers that enables functional regeneration and subsequent transplantation.
METHODS
Partial swine livers were perfused with autologous blood after being procured from healthy pigs following 70% in-vivo resection, leaving only the right lateral lobe. Partial human livers were recovered from patients undergoing anatomic right or left hepatectomies and perfused with a blood based perfusate together with various medical additives. Assessment of physiologic function during perfusion was based on markers of hepatocyte, cholangiocyte, vascular and immune compartments, as well as histology.
RESULTS
Following the development phase with partial swine livers, 21 partial human livers (14 right and 7 left hemi-livers) were perfused, eventually reaching the targeted perfusion duration of 1 week with the final protocol. These partial livers disclosed a stable perfusion with normal hepatic function including bile production (5-10 mL/h), lactate clearance, and maintenance of energy exhibited by normal of adenosine triphosphate (ATP) and glycogen levels, and preserved liver architecture for up to 1 week.
CONCLUSION
This pioneering research presents the inaugural evidence for long-term machine perfusion of partial livers and provides a pathway for innovative and relevant clinical applications to increase the availability of organs and provide novel approaches in hepatic oncology.
Identifiants
pubmed: 34334640
doi: 10.1097/SLA.0000000000005102
pii: 00000658-202111000-00022
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
836-842Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest: E.T.H. (Swiss Federal Institute of Technology in Zurich) (M. H., M. J. S., B. B., P. RvR., D.B.) and the University of Zurich (D.E., P.D., L.B.B. and P-A. C.) own/applied for patents on liver perfusion technology (PCT/EP2019/051252, PCT/EP20 17/068506). The authors report no other conflicts of interest.
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