Ischaemia-free liver transplantation in humans: a first-in-human trial

Abstract

Summary Background Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences. Methods Ischaemia-free liver transplantation (IFLT) comprises surgical techniques enabling continuous oxygenated blood supply to the liver of brain-dead donor during procurement, preservation, and implantation using normothermic machine perfusion technology. In this non-randomised study, 38 donor livers were transplanted using IFLT and compared to 130 conventional liver transplants (CLT). Findings Two recipients (5•3%) in the IFLT group experienced early allograft dysfunction, compared to 50•0% in patients receiving conventional transplants (absolute risk difference, 44•8%; 95% confidence interval, 33•6-55•9%). Recipients of IFLT had significantly reduced median (IQR) peak aspartate aminotransferase levels within the first week compared to CLT recipients (365, 238-697 vs 1445, 791-3244 U/L, p<0•001); likewise, median total bilirubin levels on day 7 were significantly lower (2•34, 1•39-4•09 mg/dL) in the IFLT group than in the CLT group (5•10, 1•90-11•65 mg/dL) (p<0•001). Moreover, IFLT recipients had a shorter median intensive care unit stay (1•48, 0•75-2•00 vs 1•81, 1•00-4•58 days, p=0•006). Both one-month recipient (97•4% vs 90•8%, p=0•302) and graft survival (97.4% vs 90•0%, p=0•195) were better for IFLT than CLT, albeit differences were not statistically significant. Subgroup analysis showed that the extended criteria donor livers transplanted using the IFLT technique yielded faster post-transplant recovery than did the standard criteria donor livers transplanted using the conventional approach. Interpretation IFLT provides a novel approach that may improve outcomes, and allow the successful utilisation of extended criteria livers. Funding This study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial international Cooperation Base of Science and Technology. Panel: Research in context

Normothermic regional perfusion in liver transplantation from donation after cardiocirculatory death: Technical, biochemical, and regulatory aspects and review of literature

“…31 NRP cannot avoid a variable period of CIT. The wide adoption of strategy such "ischemia-free liver transplantation", 71 where the graft is placed on a normothermic circuit during procurement procedure until implantation, could represent a strategy to mitigate IRI. 72,73 To date, there are no definitive criteria for graft selection during NRP: transaminases have failed to predict clinical outcome in LT: AST and ALT levels do not correlate with poor outcome and the appropriate threshold value is not clear.…”

One Shoot, Two Birds: Alleviating Inflammation Caused by Ischemia/Reperfusion Injury to Reduce the Recurrence of Hepatocellular Carcinoma

“…With the innovations of surgical techniques and NMP, the technique named ischemia-free liver transplantation (IFLT) has been created. Its application is able to procure, preserve, and implant liver grafts from DBD donors without stopping the blood and oxygen supply, thus entirely preventing hepatic IRI ( 26 ). A recent propensity-matched cohort study showed that IFLT recipients had a higher RFS rate at 1 and 3 years (92.2% and 86.7%) than conventional LT recipients (88.1% and 53.6%), with much lower liver damage ( 27 ).…”

Ischemia-free organ transplantation − a review

“…In 2021, our group published the first single-center, nonrandomized, controlled trial of IFLT [21 ▪▪ ]. The primary end-point was early allograft dysfunction (EAD) as defined by Olthoff et al [22].…”

“…Importantly, IFLT recipients of ECD livers had reduced liver injury and EAD incidence compared to those CLT recipients of standard criteria livers. Due to the small sample size, these differences were not significant [21 ▪▪ ]. In 2019, our group initiated the first randomized, controlled trial comparing IFLT and CLT in the setting of postmortem liver transplantation [23].…”