Donation after circulatory death (DCD) organs are associated with compromised transplant outcomes and limited utilization. Normothermic regional perfusion (NRP) has been shown to significantly improve organ quality and transplant outcomes. Our group previously demonstrated the feasibility and efficacy of ischemia‐free liver implantation (IFLI) using grafts from donation after brain death. We hypothesized that NRP sequential IFLI would be feasible and effective in DCD liver transplantation. This study presents clinical case attempts that validate the viability of this hypothesis.

We report the first case of IFLI of a DCD liver following NRP. The graft was donated by a 75‐year‐old man with a total warm ischemia time of 24 min. The abdominal organs underwent 67 min of NRP. The liver was then cold‐stored in University of Wisconsin solution and transported, with a total cold ischemia time of 548 min. After back‐table preparation, the liver was subjected to 373 min of normothermic machine perfusion (NMP) before being implanted using an ischemia‐free implant technique.

Perfusion parameters, lactate clearance, and liver enzyme levels during in situ NRP indicated that the liver was transplantable. In addition, perfusion parameters, lactate clearance, and bile production during ex situ NMP fulfilled the VITTAL criteria for transplantation. The recipient was a 65‐year‐old woman with primary biliary cirrhosis. The peak post‐transplant alanine aminotransferase level was 77 U/L, and liver function normalized within 9 days after surgery. The patient recovered uneventfully, with no evidence of early allograft dysfunction or other major complications, and was discharged on day 16 post‐transplantation.

This first report demonstrates the feasibility of NRP sequential IFLI in DCD liver transplantation.

Further optimization and improvement of normothermic machine perfusion (NMP) is necessary, as it can still lead to ischemia injury in transplanted livers. We propose a novel method, termed ischemia‐free liver implantation (IFLI), which maintains a constant blood supply throughout both the preservation and implantation processes. This study aimed to evaluate the feasibility and safety of IFLI compared to NMP.

Thirty‐four recipients of IFLI and 17 recipients of NMP were enrolled. The recovery of liver function, complication rates, and survival outcomes were compared between the groups.

The mean cold ischemia time (CIT), anhepatic time, and surgical duration were 5.94 ± 0.41 h, 50.59 ± 2.10 min, and 439.32 ± 13.25 min for the IFLI group, and 6.29 ± 0.52 h, 54.65 ± 4.32 min, and 428.06 ± 22.04 min for the NMP group (p = 0.333, 0.086, and 0.135, respectively). The IFLI group had a significantly lower incidence of post‐reperfusion syndrome compared to the NMP group (8% vs. 58.8%, p < 0.001), and the incidence rate of PNF was higher in the NMP group (p = 0.041).

IFLI, by maintaining constant blood supply during implantation, avoids re‐ischemia‐reperfusion injury (re‐IRI) and demonstrates improved postoperative liver function recovery, fewer complications, and greater safety compared to standard NMP.