Partial liver grafts from ex situ splitting are considered marginal due to prolonged static cold storage. The use of ex situ hypothermic oxygenated perfusion (HOPE) may offer a strategy to improve preservation of ex situ split grafts. In this single‐center pilot study, we prospectively performed ex situ liver splitting during HOPE (HOPE–Split) for adult and pediatric partial grafts over a 1‐year period (November 1, 2020 to December 1, 2021). The primary safety endpoint was based on the number of liver graft–related adverse events (LGRAEs) per recipient, including primary nonfunction, biliary complications, hepatic vascular complications, and early relaparotomies and was compared with consecutive single‐center standard ex situ split transplantations (Static–Split) performed from 2018 to 2020. Secondary endpoints included preservation characteristics and early outcomes. Sixteen consecutive HOPE–Split liver transplantations (8 HOPE–Split procedures) were included and compared with 24 Static–Splits. All HOPE–Split grafts were successfully transplanted, and no graft loss nor recipient death was encountered during the median follow‐up of 7.5 months (interquartile range, 5.5–12.5). Mean LGRAE per recipient was similar in both groups (0.31 ± 0.60 vs. 0.46 ± 0.83; p = 0.78) and split duration was not significantly increased for HOPE–Split (216 vs. 180 min; p = 0.45). HOPE–Split grafts underwent perfusion for a median of 125 min, which significantly shortened static cold storage (472 vs. 544 min; p = 0.001), whereas it prolonged total ex vivo preservation (595 vs. 544 min; p = 0.007) and reduced neutrophil infiltration on reperfusion biopsies (p = 0.04) compared with Static–Split. This clinical pilot study presents first feasibility and safety data for transplantation of partial liver grafts undergoing ex situ split during HOPE and suggests improved preservation compared with static ex situ splitting. These preliminary results will allow to set up large‐scale trials on the use of machine perfusion in pediatric and split‐liver transplantation.

In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly.