Portable hypothermic oxygenated machine perfusion for organ preservation in liver transplantation: A randomized, open-label, clinical trial

Background and Aims:In liver transplantation, cold preservation induces ischemia, resulting in significant reperfusion injury. Hypothermic oxygenated machine perfusion (HMP-O2) has shown benefits compared to static cold storage (SCS) by limiting ischemia-reperfusion injury. This study reports outcomes using a novel portable HMP-O2 device in the first US randomized control trial.Approach and Results:The PILOT trial (NCT03484455) was a multicenter, randomized, open-label, noninferiority trial, with participants randomized to HMP-O2 or SCS. HMP-O2 livers were preserved using the Lifeport Liver Transporter and Vasosol perfusion solution. The primary outcome was early allograft dysfunction. Noninferiority margin was 7.5%. From April 3, 2019, to July 12, 2022, 179 patients were randomized to HMP-O2 (n=90) or SCS (n=89). The per-protocol cohort included 63 HMP-O2 and 73 SCS. Early allograft dysfunction occurred in 11.1% HMP-O2 (N=7) and 16.4% SCS (N=12). The risk difference between HMP-O2 and SCS was -5.33% (one-sided 95% upper confidence limit of 5.81%), establishing noninferiority. The risk of graft failure as predicted by Liver Graft Assessment Following Transplant score at seven days (L-GrAFT7) was lower with HMP-O2 [median (IQR) 3.4% (2.4-6.5) vs. 4.5% (2.9-9.4), p=0.024]. Primary nonfunction occurred in 2.2% of all SCS (n=3, p=0.10). Biliary strictures occurred in 16.4% SCS (n=12) and 6.3% (n=4) HMP-O2 (p=0.18). Nonanastomotic biliary strictures occurred only in SCS (n=4).Conclusions:HMP-O2 demonstrates safety and noninferior efficacy for liver graft preservation in comparison to SCS. Early allograft failure by L-GrAFT7 was lower in HMP-O2, suggesting improved early clinical function. Recipients of HMP-O2 livers also demonstrated a lower incidence of primary nonfunction and biliary strictures, although this difference did not reach significance.