Trapianto di fegato da donazione controllata a cuore fermo con perfusione regionale normotermica: risultati e implicazioni per la pratica italiana.

Background: Donation after circulatory death (DCD) has the potential to increase the pool of available donors. DCD liver transplantation (LTx) has been linked to poorer outcomes compared to donation after brainstem death (DBD), but normothermic regional perfusion (NRP) has the potential to reverse the deleterious effects of warm ischemia (WIT) and allow better outcomes. We test the hypothesis that outcomes of DCD-NRP LTx are non-inferior to DBD, even when the WIT is long. Methods: All patients undergoing LTx at Cambridge University Hospital from January 2015 to October 2020 were included, except for recipients of grafts further assessed with normothermic machine perfusion (NMP). Descriptive and regression analyses were conducted among NRP, DCD with standard cold storage (SCS) and DBD cohorts. Secondarily, an extended cohort of only NRP-DCD LTx from January 2015 to April 2023 was analysed to detect potential differences in outcomes between grafts retrieved with asystolic times exceeding or not exceeding 20 minutes. Results: 61 DCD-SCS, 63 NRP and 344 DBD LTx were included. NRP livers proved better than SCS in terms of early function, with an estimated reduction in the mean model for early allograft function score of -1.66 (p<0.001) compared to SCS and -1.80 compared to DBD (p<0.001). Kidney function was also improved, resulting in a lower risk-adjusted peak-to-baseline creatinine ratio compared to SCS (p=0.005) and in a minor incidence of post-operative AKI compared to DBD (p=0.023). Less non-anastomotic strictures (NAS) were recorded when compared to SCS (6.7% vs 26.3%, p=0.009), with 72% inferior risk-adjusted odds to develop NAS overall. No differences in terms of biliary complications were find between NRP and DBD groups. The risk-adjusted transplant survival at 5 years was better in the NRP cohort, with a 62% less risk of transplant failure compared to SCS (HR 0.38, p=0.037). The other survival outcomes were similar at 5 years. No significant differences were found in the outcomes between LTx from NRP livers with ≥ or < 20 minutes of asystolic times, apart from a higher incidence of anastomotic biliary strictures in the group with longer WIT (p=0.047). Conclusion: NRP LTx yelds outcomes similar to DBD and meets current benchmarks for liver transplant activity. The systematic use of ex situ perfusion is unnecessary in case of good NRP parameters, even in case of asystolic times > 20 minutes, and should be reserved for cases where NRP performance is unsatisfactory or prolonged CIT is anticipated.