Effect of extended cold ischaemia with UW solution on graft function after liver transplantation

doi:10.1016/0140-6736(92)92559-X

The Lancet

Volume 340, Issue 8832, 5 December 1992, Pages 1373-1376

https://doi.org/10.1016/0140-6736(92)92559-X Get rights and content

Abstract

Studies in animals on the use of UW solution in liver transplantation have shown an inverse relation between cold ischaemia time (CIT) and graft function. There are few clinical data on this relation in human beings. We have investigated the effect of extended cold ischaemia in a prospective study. We assessed early graft function and subsequent outcome for 306 consecutive elective liver transplantations; for analyses, grafts were grouped according to CIT (< 12 h group A, ≥ 12 h group B), since a preliminary study identified 12 h as a significant cut-off point. Initial graft function was better in group A than group B, as shown by maximum alanine aminotransferase activity (mean 623 [805] vs 946 [1148], p = 0·02), bile production on days 1-3 (p < 0·05), maximum serum bilirubin by day 10 (206 [166] vs 244 [163] μmol/l, p = 0·04), and frequencies of primary non-function (1 [0·4%] vs 4 [7%], p = 0·006) and hepatocyte necrosis on routine biopsy sample after reperfusion (18% vs 31 %, p = 0·04). Long-term outcome was also better in group A than group B; graft and patient survival rates were higher and fewer retransplantations were needed. These findings suggest that cold ischaemia in UW solution for longer than 12 h is a risk factor for graft function and patient survival. We recommend that the limit of the safe CIT be reconsidered.

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Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective studies are very limited. In this monocentric, open-label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft-related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p = .007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p = .05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival one year after LT (p = .03, log-rank test). In addition, patients in the SCS group had a higher re-admission and overall complication rate at si months, in particular cardio-vascular adverse events (p = .04 and p = .03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival.
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Cold ischemia time (CIT) is one of the most significant variables affecting graft survival after liver transplantation. The aim of this study was to identify other predictors of worse graft survival depending on the duration of cold ischemia.
This retrospective cohort study included data of liver transplant recipients and donors in the period from 2014 to 2019. A total of 724 patients were analyzed after excluding retransplatations and urgent operations. Using receiver operating characteristic analysis, we identified CIT value which divides into 2 clinically different subgroups with respect to 5-year graft loss. Within those 2 subgroups, we performed Cox proportional hazard analysis with time to graft loss as endpoint.
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Predictive ability of well-known risk factors for worse outcomes after liver transplantation depend on the length of cold ischemia.
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Cold storage is a common procedure for liver preservation in a transplant setting. However, during cold ischemia, the liver suffers molecular alterations that can affect its performance. Also, deleterious mechanisms set forth in the storage phase are exacerbated during reperfusion. This study aimed to identify liver proteins associated with injury during cold storage and/or normothermic reperfusion using the isolated perfused rat liver model. Livers from male rats were subjected to either (1) cold storage for 24 h, (2) ex vivo normothermic reperfusion for 90 min or (3) cold storage for 24 h followed by ex vivo normothermic reperfusion for 90 min. Then, the livers were homogenized and proteins were extracted. Protein expression between each experimental group and the control (freshly resected livers) was compared by two-dimensional (2D) gel electrophoresis. Protein identification was carried out by matrix‐assisted laser desorption/ionization time‐of‐flight spectrometry (MALDI‐TOF/TOF) using MASCOT as the search engine. 23 proteins were detected with significantly altered levels of expression among the different treatments, including molecular chaperones, antioxidant enzymes, and proteins involved in energy metabolism. Some of them have been postulated as biomarkers for liver damage while others had been identified in other organs subjected to ischemia and reperfusion injury. The whole data set will be a useful resource for studying deleterious molecular mechanisms that result in diminished liver function during storage and subsequent reperfusion.
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2018, Transplantation Reviews
In recent years, remarkable progress has occurred in the development of technologies to support ex situ liver perfusion. Building upon extensive preclinical studies in large animal models, pilot and randomized clinical trials have been initiated, and preliminary outcomes suggest more optimal protection of both standard and extended criteria liver grafts. There currently exists an incredible opportunity and need to further refine this technology, determine appropriate viability measures to predict usable liver grafts, and to explore potent protective additive strategies to further optimize the quality of extended criteria organs. These findings will have major bearing in expanding the limited liver donor pool, and may save lives where up to a quarter of listed patients die on wait-lists. Herein we offer a brief overview of the history and current status of ex situ liver perfusion, and discuss future directions that will likely have major impact on the practice of clinical liver transplantation.

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ORIGINAL ARTICLESEffect of extended cold ischaemia with UW solution on graft function after liver transplantation

Abstract

Seventy two hour preservation of the canine pancreas

Transplantation

An analysis of the components of UW solution using the isolated perfused rabbit liver

Transplantation

Extended preservation of the liver for clinical transplantation

Lancet

Principles of solid organ preservation by cold storage

Transplantation

Reduced-size orthotopic liver graft in hepatic transplantation in children

Surgery

Emergency orthotopic liver transplantation in two patients using one donor liver

Br J Surg

Extended preservation of human liver grafts with UW solution

JAMA

Comparison of UW solution and Euro-Collins solutions for cold preservation of human liver grafts

Transplantation

A comparison of UW with Eurocollins preservation solution in liver transplantation

Transplantation

The impact of extended preservation on clinical liver transplantation

Transplantation

ORIGINAL ARTICLES
Effect of extended cold ischaemia with UW solution on graft function after liver transplantation