Sequential hypothermic and normothermic machine perfusion enables safe transplantation of high-risk donor livers

Abstract

Ex situ normothermic machine perfusion (NMP) is increasingly used for viability assessment of high-risk donor livers, whereas dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia-reperfusion injury. We aimed to resuscitate and test the viability of initially-discarded, high-risk donor livers using sequential DHOPE and NMP with two different oxygen carriers: an artificial hemoglobin-based oxygen carrier (HBOC) or red blood cells (RBC). In a prospective observational cohort study of 54 livers that underwent DHOPE-NMP, the first 18 procedures were performed with a HBOC-based perfusion solution and the subsequent 36 procedures were performed with an RBC-based perfusion solution for the NMP phase. All but one livers were derived from extended criteria donation after circulatory death donors, with a median donor risk index of 2.84 (IQR 2.52-3.11). After functional assessment during NMP, 34 livers (63% utilization), met the viability criteria and were transplanted. One-year graft and patient survival were 94% and 100%, respectively. Post-transplant cholangiopathy occurred in 1 patient (3%). There were no significant differences in utilization rate and post-transplant outcomes between the HBOC and RBC group. Ex situ machine perfusion using sequential DHOPE-NMP for resuscitation and viability assessment of high-risk donor livers results in excellent transplant outcomes, irrespective of the oxygen carrier used.

Keywords: clinical research / practice; donation after circulatory death (DCD); donors and donation; liver transplantation / hepatology; organ perfusion and preservation.

FIGURE 1

Schematic overview of combined DHOPE and NMP procedures. Initially discarded donor livers either underwent the combination of DHOPE, controlled oxygenation rewarming and NMP with a HBOC or RBC‐based perfusion solution. In the RBC group, a switch of perfusion solution was performed between DHOPE and the rewarming phase, whereas in the HBOC group no switch was required. COR, controlled oxygenated rewarming; DHOPE, dual hypothermic oxygenated machine perfusion; HBOC, hemoglobin‐based oxygen carrier; NMP, normothermic machine perfusion; UW MPS, UW machine perfusion solution [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Biochemical viability parameters during NMP. (A) Perfusate lactate levels were significantly lower after 30 min of NMP in the transplanted livers. (B) Perfusate pH was normalized more rapidly in the transplanted livers. (C‐F) Bile pH, delta pH, delta HCO₃ ⁻, and delta glucose were higher in the transplanted livers. Delta for pH, HCO₃ ⁻, and glucose was calculated between the bile and the arterial value, at the same time point. * Indicates a statistically significant difference p < .05. **p < .01, ***p < .001, **** p < .0001. The statistical tests were not powered due to small sample size, these results should be interpreted with caution. NMP, normothermic machine perfusion; Tx, transplanted; No Tx, not transplanted [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Machine perfusion characteristics. (A) Perfusate lactate levels were significantly lower at the start of NMP in the RBC perfused livers. After 90 min of NMP, the difference was no longer observed. (B‐E) Perfusate pH, delta pH, delta HCO₃, and delta glucose were all comparable between both groups. Delta for pH, HCO₃, and glucose was calculated between the arterial and bile value, at the same time point. (F) Utilization rate for both groups was similar (67% vs. 61% p = .693). * Indicates a statistically significant difference p < .05. ** p < .01, *** p < .001, **** p < .0001. The statistical tests were not powered due to small sample size, these results should be interpreted with caution. HBOC‐201, hemoglobin‐based oxygen carrier 201; RBC, red blood cells [Color figure can be viewed at wileyonlinelibrary.com]