Perfusate Analysis During Dual Hypothermic Oxygenated Machine Perfusion of Liver Grafts: Correlations With Donor Factors and Early Outcomes

Abstract

Background. Liver graft viability assessment has long been considered a limit of hypothermic oxygenated machine perfusion (HOPE). Aim of this study was assessing correlations of easily available perfusate parameters (PP) (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, glucose, lactate, and pH) with graft features and outcome. Methods. In the period October 2018–February 2020, perfusate samples were obtained every 30 minutes during 50 dual-HOPE (D-HOPE) procedures. Correlations of PP with graft factors, 90-day graft loss, early allograft dysfunction (EAD), L-GrAFT score, acute kidney injury, and comprehensive complication index were analyzed using Pearson coefficient, receiver-operating characteristics analysis and by univariable and multivariable regression. Results. Median D-HOPE time was 122 minutes. All parameters were normalized to liver weight. Only macrovesicular steatosis (MaS) significantly impacted PP levels and slope. Grafts with ≥30% MaS exhibited significantly different PP values and slope. Graft loss and EAD rate were 2% (n = 1) and 26% (n = 13). All PP except lactate correlated with EAD, 90-minute alanine aminotransferase showing the highest area under the receiver-operating characteristics curve (0.84). However, at multivariable analysis, the only factor independently associated with EAD was MaS (odds ratio, 5.44; confidence interval, 1.05-28.21; P = 0.04). Ninety minutes lactate dehydrogenase had the strongest correlation with L-GrAFT (R = 0.70; P < 0.001). PP correlated poorly with comprehensive complication index and grades 2–3 acute kidney injury rate. Conclusions. PP were predictive of graft function after transplant, but their association with graft survival and clinical outcomes requires further evaluation. MaS influenced levels of PP and was the only independent predictor of EAD.

Decoding the single-cell landscape and intercellular crosstalk in the transplanted liver: a 4-dimension mouse model

“…The emergence of the peaks of aminotransferases in our model was consistent with most of previous studies [18, 31]. Also, the graft injury would be affected by multiple factors such as ischemia time and perfusate, causing diversity in graft recovery [32, 33]. Stable phase showed a well recovered liver function after the acute graft injury, which probably started from 3D after LT. Then we conducted a single cell technology for the in-depth understanding of graft remodeling in both acute and stable phases.…”

Viability Assessment in Liver Transplantation—What Is the Impact of Dynamic Organ Preservation?

“…Such findings parallel earlier studies, where similar correlation between perfusate and recipient plasma transaminases were demonstrated with however limited further impact on complications [90,91]. Recently, Patrono et al published the results of a single-center retrospective study on 50 patients, who received a DBD liver transplantation after D-HOPE [18]. Their data showed a negative correlation between lactate and pH explained by the fact that lactate Similarly to NMP, perfusion flow, pressures, and resistance are routinely measured, but rarely considered as single criterion for viability testing [1,8].…”

“…[10]. Although hypothermic technologies are frequently considered less helpful to assess liver viability, the same molecules found in NMP perfusates can also be identified during cold or subnormothermic liver perfusion (Figures 1, 3 and 4) [18,23,38,50,65,90].…”

“…Recently, Patrono et al published the results of a single-center retrospective study on 50 patients, who received a DBD liver transplantation after D-HOPE [18]. Their data showed a negative correlation between lactate and pH explained by the fact that lactate accumulates during CS as a product of anaerobic glycolysis and when it is subsequently released in the perfusate it determines a reduction of pH.…”

“…Therefore, most authors suggest a combination of "viability" tests, by composite scores based on quantification of different perfusates parameters [12][13][14][15][16][17]. However, as most series have only a limited number of events, the correlation of biomarkers with postsurgical outcome remains difficult [18][19][20][21][22][23]. In this article, we first discuss the clinical relevance of individual parameters, considered for viability testing during machine perfusion before liver transplantation.…”