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Dual hypothermic oxygenated perfusion (DHOPE) is increasingly being used to extend liver preservation to improve transplant logistics. However, little is known about its benefits in high-risk liver grafts. This study aimed to investigate whether prolonged DHOPE provides benefits other than improved logistics in all liver types. We performed a national retrospective cohort study of 177 liver transplants from 12 Italian centers preserved with DHOPE for ≥4 hours between 2015 and 2022. A control group of 177 DHOPEs of <4 hours during the same period was created using 1:1 propensity score matching. The impact of risk profiles and preservation times on the outcomes was assessed using univariable and multivariable regression models. No significant differences in posttransplant outcomes were found between prolonged and short DHOPEs. However, the prolonged group had a significantly lower incidence of posttransplant acute kidney injury (AKI) compared to the short group (30.5% vs. 44.6%, p = 0.008). Among prolonged DHOPEs, no differences in transplant outcomes were observed according to donor risk index, Eurotransplant definition for marginal grafts, and balance of risk score. DHOPE duration was associated with a lower risk of AKI in multivariable models adjusted for donor risk index, Eutrotransplant marginal grafts, and balance of risk score. Prolonged hypothermic oxygenated perfusion confirmed its protective effect against AKI in a multivariable model adjusted for donor and recipient risk factors [OR: 0.412, 95% CI: 0.200-0.850, p = 0.016]. Prolonged DHOPE is widely used to improve transplant logistics, provides good results with high-risk grafts, and appears to be associated with a lower risk of posttransplant AKI. These results provide further insight into the important role of DHOPE in preventing posttransplant complications., (Copyright © 2024 American Association for the Study of Liver Diseases.)

The primary aim of this single-center, phase 1 exploratory study was to investigate the safety, feasibility, and impact on intrahepatic hemodynamics of a fresh frozen plasma (FFP)-based perfusate in ex situ liver normothermic machine perfusion (NMP) preservation. Using an institutionally developed perfusion device, 21 livers (13 donations after brain death and 8 donations after circulatory death) were perfused for 3 hours 21 minutes to 7 hours 52 minutes and successfully transplanted. Outcomes were compared in a 1:4 ratio to historical control patients matched according to donor and recipient characteristics and preservation time. Perfused livers presented a very low resistance state with high flow during ex situ perfusion (arterial and portal flows 340 ± 150 and 890 ± 70 mL/minute/kg liver, respectively). This hemodynamic state was maintained even after reperfusion as demonstrated by higher arterial flow observed in the NMP group compared with control patients (220 ± 120 versus 160 ± 80 mL/minute/kg liver, P = 0.03). The early allograft dysfunction (EAD) rate, peak alanine aminotransferase (ALT), and peak aspartate aminotransferase (AST) levels within 7 days after transplantation were lower in the NMP group compared with the control patients (EAD 19% versus 46%, P = 0.02; peak ALT 363 ± 318 versus 1021 ± 999 U/L, P = 0.001; peak AST 1357 ± 1492 versus 2615 ± 2541 U/L, P = 0.001 of the NMP and control groups, respectively). No patient developed ischemic type biliary stricture. One patient died, and all other patients are alive and well at a follow-up of 12-35 months. No device-related adverse events were recorded. In conclusion, with this study, we showed that ex situ NMP of human livers can be performed safely and effectively using a noncommercial device and an FFP-based preservation solution. Future studies should further investigate the impact of an FFP-based perfusion solution on liver hemodynamics during ex situ normothermic machine preservation., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Ex situ normothermic machine perfusion (NMP) might minimize ischemia/reperfusion injury (IRI) of liver grafts. In this study, 20 primary liver transplantation recipients of older grafts (≥70 years) were randomized 1:1 to NMP or cold storage (CS) groups. The primary study endpoint was to evaluate graft and patient survival at 6 months posttransplantation. The secondary endpoint was to evaluate liver and bile duct biopsies; IRI by means of peak transaminases within 7 days after surgery; and incidence of biliary complications at month 6. Liver and bile duct biopsies were collected at bench surgery, end of ex situ NMP, and end of transplant surgery. Interleukin (IL) 6, IL10, and tumor necrosis factor α (TNF-α) perfusate concentrations were tested during NMP. All grafts were successfully transplanted. Median (interquartile range) posttransplant aspartate aminotransferase peak was 709 (371-1575) IU/L for NMP and 574 (377-1162) IU/L for CS (P = 0.597). There was 1 hepatic artery thrombosis in the NMP group and 1 death in the CS group. In NMP, we observed high TNF-α perfusate levels, and these were inversely correlated with lactate (P < 0.001). Electron microscopy showed decreased mitochondrial volume density and steatosis and an increased volume density of autophagic vacuoles at the end of transplantation in NMP versus CS patients (P < 0.001). Use of NMP with older liver grafts is associated with histological evidence of reduced IRI, although the clinical benefit remains to be demonstrated., (Copyright © 2018 by the American Association for the Study of Liver Diseases.)