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Steatotic Livers Are More Susceptible to Ischemia Reperfusion Damage after Transplantation and Show Increased γδ T Cell Infiltration
Eggenhofer, Elke, Groell, Anja, Junger, Henrik, Kasi, Amoon, Kroemer, Alexander, Geissler, Edward K., Schlitt, Hans J.
and Scherer, Marcus N.
(2021)
Steatotic Livers Are More Susceptible to Ischemia Reperfusion Damage after Transplantation and Show Increased γδ T Cell Infiltration.
IJMS 22 (2036), pp. 1-12.
Date of publication of this fulltext: 01 Mar 2021 11:50
Article
DOI to cite this document: 10.5283/epub.44490
Abstract
Liver transplantation (LTx) is often the only possible therapy for many end-stage liver diseases, but successful long-term transplant outcomes are limited by multiple factors, including ischemia reperfusion injury (IRI). This situation is aggravated by a shortage of transplantable organs, thus encouraging the use of inferior quality organs. Here, we have investigated early hepatic IRI in a ...
Liver transplantation (LTx) is often the only possible therapy for many end-stage liver diseases, but successful long-term transplant outcomes are limited by multiple factors, including ischemia reperfusion injury (IRI). This situation is aggravated by a shortage of transplantable organs, thus encouraging the use of inferior quality organs. Here, we have investigated early hepatic IRI in a retrospective, exploratory, monocentric case-control study considering organ marginality. We analyzed standard LTx biopsies from 46 patients taken at the end of cold organ preparation and two hours after reperfusion, and we showed that early IRI was present after two hours in 63% of cases. Looking at our data in general, in accordance with Eurotransplant criteria, a marginal transplant was allocated at our institution in about 54% of cases. We found that patients with a marginal-organ LTx showing evidence of IRI had a significantly worse one-year survival rate (51% vs. 75%). As we saw in our study cohort, the marginality of these livers was almost entirely due to steatosis. In contrast, survival rates in patients receiving a non-marginal transplant were not influenced by the presence or absence of IRI. Poorer outcomes in marginal organs prompted us to examine pre- and post-reperfusion biopsies, and it was revealed that transplants with IRI demonstrated significantly greater T cell infiltration. Molecular analyses showed that higher mRNA expression levels of CXCL-1, CD3 and TCR gamma locus genes were found in IRI livers. We therefore conclude that the marginality of an organ, namely steatosis, exacerbates early IRI by enhancing effector immune cell infiltration. Preemptive strategies targeting immune pathways could increase the safety of using marginal organs for LTx.
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| Item type | Article | ||||
| Journal or Publication Title | IJMS | ||||
| Publisher: | MDPI | ||||
|---|---|---|---|---|---|
| Open Access Type: | Gold (with APC) | ||||
| Place of Publication: | BASEL | ||||
| Volume: | 22 | ||||
| Number of Issue or Book Chapter: | 2036 | ||||
| Page Range: | pp. 1-12 | ||||
| Date | 18 February 2021 | ||||
| Institutions | Medicine > Lehrstuhl für Chirurgie | ||||
| Identification Number |
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| Keywords | liver transplantation; ischemia; reperfusion injury; marginal organs; T cells | ||||
| Dewey Decimal Classification | 600 Technology > 610 Medical sciences Medicine | ||||
| Status | Published | ||||
| Refereed | Yes, this version has been refereed | ||||
| Created at the University of Regensburg | Yes | ||||
| URN of the UB Regensburg | urn:nbn:de:bvb:355-epub-444907 | ||||
| Item ID | 44490 |
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