Importance: Normothermic machine perfusion (NMP) has been shown to reduce peritransplant complications. Despite increasing NMP use in liver transplant (LT), there is a scarcity of real-world clinical experience data.Objective: To compare LT outcomes between donation after brain death (DBD) and donation after circulatory death (DCD) allografts preserved with NMP or static cold storage (SCS).Design, Setting, and Participants: This single-center, retrospective observational cohort study included all consecutive adult LTs performed between January 2019 and December 2023 at the Mayo Clinic in Arizona. Data analysis was performed between February 2024 and June 2024. Outcomes of DBD-SCS, DBD-NMP, DCD-SCS, and DCD-NMP transplants were compared.Exposure: DBD and DCD livers preserved on NMP or SCS.Main Outcomes and Measures: The primary outcomes were early allograft dysfunction (EAD), intraoperative transfusion, and post-LT hospital resource use, including length of stay (LOS) and readmissions. Secondary outcomes included acute kidney injury (AKI) and 1-year graft and patient survival.Results: A total of 1086 LTs were included in the following 4 groups: DBD-SCS (n = 480), DBD-NMP (n = 63), DCD-SCS (n = 264), and DCD-NMP (n = 279). Among LT recipients, median (IQR) age was 60.0 years (52.0-66.0); 399 LT recipients (36.7%) were female. DCD-NMP had the lowest EAD rate (17.5%), followed by DCD-SCS (50.0%), DBD-NMP (36.8%), and DBD-SCS (27.3%) (P < .001). DCD-NMP had the lowest intraoperative transfusion requirement compared to all other groups. Hospital and intensive care unit (ICU) LOS were shortest in DCD-NMP (median [IQR] hospital LOS, 5.0 days [4.0-7.0]; P = .01; median [IQR] ICU LOS, 1.5 days [1.2-3.1]; P = .01). One-year cumulative readmission probability was 86% lower for DCD-NMP vs DCD-SCS (95% CI, 0.09-0.22; P < .001) and 53% lower for DBD-NMP vs DBD-SCS (95% CI, 0.26-0.87; P < .001). AKI events were lower in DCD-NMP (31.1%) vs DCD-SCS (47.4%) (P = .001). Compared to SCS, the NMP group had a 78% overall reduction in graft failure (hazard ratio [HR], 0.22; 95% CI, 0.10-0.49; P < .001). For those receiving DCD allografts, the risk reduction was even more pronounced, with an 87% decrease in graft failure (HR, 0.13; 95% CI, 0.05-0.33; P < .001). NMP was significantly protective from patient mortality vs SCS (HR, 0.31; 95% CI, 0.12-0.80; P = .02).Conclusions and Relevance: In this observational high-volume cohort study, NMP significantly improved LT clinical outcomes and reduced hospital resource use, especially in DCD allografts. NMP may enhance access to LT by addressing the challenges historically linked with DCD liver use.

Background Given the potentially additive risk from using donor livers that are both steatotic and from a donation after circulatory death(DCD) donor, there is a paucity of data on the outcome of DCD liver transplantation(LT) utilizing livers with macrosteatosis. Methods All DCD LT performed at Mayo Clinic‐Florida, Mayo Clinic‐Arizona and Mayo Clinic‐Rochester from 1999‐2019 were included(N=714). Recipients of DCD LT were divided into 3 groups: those with Moderate Macrosteatosis(30‐60%), Mild Macrosteatosis(5‐30%) and No Steatosis. Results Patients with Moderate Macrosteatosis had a higher rate of post‐reperfusion syndrome (PRS)(53.9% vs. 26.2%;p=0.002), post‐reperfusion cardiac arrest(7.7% vs.0.3%;p<0.001), primary non‐function(PNF)(7.7%vs.1.0%;p=0.003), early allograft dysfunction(EAD)(70.8%vs.45.6% and 8.3%;p=0.02) and acute kidney injury (AKI)(39.1%vs.19.4%; p=0.02) than patients with No Steatosis. No difference in any of the peri‐operative complications was seen between the Mild Macrosteatosis and the No Steatosis groups except for the rate of EAD(56.8%vs.45.6%;p=0.04). No difference in ischemic cholangiopathy(IC), vascular thrombosis/stenosis or graft and patient survival was seen between the three groups. Conclusion DCD donors with mild macrosteatosis <30% can be utilized with no increase in peri‐operative complications and similar patient and graft survival compared to DCD donors with no steatosis. When utilizing DCD donors with moderate macrosteatosis higher rates of PRS, PNF, post‐reperfusion cardiac arrest, EAD and AKI should be anticipated.

ClinicalTrials.gov registered (retrospectively) on 9–7-17 (NCT03276390).

Hepatocellular Carcinoma (HCC) is the most common liver malignancy and third leading cause of cancer death worldwide. For early- and intermediate-stage disease, liver-directed therapies for locoregional control, or down-staging prior to definitive surgical therapy with hepatic resection or liver transplantation, have been studied broadly, and are the mainstays of current treatment guidelines. As HCC incidence has continued to grow, and with more patients presenting with advanced disease, our current treatment modalities do not suffice, and better therapies are needed to improve disease-specific and overall survival. Until recently, sorafenib was the only systemic therapy utilized, and was associated with dismal results. The advent of immuno-oncology has been of significant interest, and has changed the paradigm of therapy for HCC. Lately, combination regimens including atezolizumab plus bevacizumab; durvalumab plus tremelimumab; and pembrolizumab plus Lenvatinib have shown impressive responses of between 25–35%; this is much higher than responses observed with single agents. Complete responses with checkpoint inhibitor therapy have been observed in advanced-stage HCC patients. These dramatic results have naturally led to several questions. Can or should checkpoint inhibitors, or other immunotherapy combinations, be used routinely before resection or transplant? Is there a synergistic effect of immunotherapy with locoregional therapy, and will pre-treatment increase disease-free survival after surgical intervention? Is it immunologically safe to use these therapies prior to transplantation? Much is still to be learned in terms of the dosing, timing, and overall utility of the use of immune checkpoint inhibitors for pre-transplant care and down-staging. More studies will be needed to understand the management of adverse events while maximizing the therapeutic window of these agents. In this review, we look at the current data on therapy with immune checkpoint inhibitors in advanced HCC, with a focus on pre-transplant treatment prior to liver transplant.