Outcome of liver transplantation with grafts from brain-dead donors treated with dual hypothermic oxygenated machine perfusion, with particular reference to elderly donors

Abstract

Prompted by the utilization of extended criteria donors, dual hypothermic oxygenated machine perfusion (D‐HOPE) was introduced in liver transplantation to improve preservation. When donors after neurological determination of death (DBD) are used, D‐HOPE effect on graft outcomes is unclear. To assess D‐HOPE value in this setting and to identify ideal scenarios for its use, data on primary adult liver transplant recipients from January 2014 to April 2021 were analyzed using inverse probability of treatment weighting, comparing outcomes of D‐HOPE‐treated grafts (n = 121) with those preserved by static cold storage (n = 723). End‐ischemic D‐HOPE was systematically applied since November 2017 based on donor and recipient characteristics and transplant logistics. D‐HOPE use was associated with a significant reduction of early allograft failure (OR: 0.24; 0.83; p = .024), grade ≥3 complications (OR: 0.57; p = .046), comprehensive complication index (−7.20 points; p = .003), and improved patient and graft survival. These results were confirmed in the subset of elderly donors (>75‐year‐old). Although D‐HOPE did not reduce the incidence of biliary complications, its use was associated with a reduced severity of ischemic cholangiopathy. In conclusion, D‐HOPE improves postoperative outcomes and reduces early allograft loss in extended criteria DBD grafts.

Hypothermic Machine Perfusion of the Liver. The Reasons for Success

“…Patrono et al demonstrated a reduction in major complications including the severity of NAS after D-HOPE treatment in more than 100 perfused grafts. The findings were confirmed in a subset of transplantations from old DBD donors 42 . Overall, there is increasing evidence that a simple endischemic HOPE-treatment is effective in the reduction of biliary complications in various grafts types, including DCD livers and other extended criteria donor grafts.…”

Viability Criteria during Liver Ex-Situ Normothermic and Hypothermic Perfusion

“…In the first clinical series published by Guarrera et al [ 23 ] transaminase peak after liver transplant positively correlated with transaminase and LDH levels in perfusate, with however limited impact on the clinical outcome and complications. Among different perfusion parameters, Patrono et al [ 54 ] found that ALT level at 90 min was the best predictor of EAD with a cutoff of 537 IU/L, although this result was not confirmed at multivariate analysis. Moreover, 90 min LDH had the highest correlation with the liver graft assessment following transplantation (L-GrAFT) risk score [ 55 ].…”

Mitochondria and Cancer Recurrence after Liver Transplantation—What Is the Benefit of Machine Perfusion?

“…Related to this reduced inflammation, the HOPE procedure further diminishes later biliary complications based on a lower release of profibrotic molecules from stellate cells and myofibroblasts after LT [ 111 , 112 ]. Whilst these findings were mainly explored in experimental and clinical studies with DCD livers, there is also some evidence in DBD grafts from elderly donors and in fatty livers, where HOPE was found to reduce IRI with subsequent improved early function and graft survival [ 67 , 113 , 114 ].…”

“…The impact of HOPE on clinical results was investigated in many studies, which consistently show the protective effects, with reduced IRI, less bile duct injury, and better graft function, with a follow-up of up to 5 years [ 107 , 114 , 115 , 116 , 117 , 118 ]. Additional evidence comes from three RCTs, which confirmed the HOPE effect, with protection from post-transplant biliary complications, EAD, high peak transaminases, and better graft survival rates in various graft types, including DCD livers [ 119 , 120 , 121 ].…”