A short period (1–2 h) of hypothermic oxygenated machine perfusion (HOPE) after static cold storage is safe and reduces ischemia‐reperfusion injury‐related complications after liver transplantation. Machine perfusion time is occasionally prolonged for logistical reasons, but it is unknown if prolonged HOPE is safe and compromises outcomes. We conducted a multicenter, observational cohort study of patients transplanted with a liver preserved by prolonged (≥4 h) HOPE. Postoperative biochemistry, complications, and survival were evaluated. The cohort included 93 recipients from 12 European transplant centers between 2014–2021. The most common reason to prolong HOPE was the lack of an available operating room to start the transplant procedure. Grafts underwent HOPE for a median (range) of 4:42 h (4:00–8:35 h) with a total preservation time of 10:50 h (5:50–20:50 h). Postoperative peak ALT was 675 IU/L (interquartile range 419–1378 IU/L). The incidence of postoperative complications was low, and 1‐year graft and patient survival were 94% and 88%, respectively. To conclude, good outcomes are achieved after transplantation of donor livers preserved with prolonged (median 4:42 h) HOPE, leading to a total preservation time of almost 21 h. These results suggest that simple, end‐ischemic HOPE may be utilized for safe extension of the preservation time to ease transplantation logistics.

Despite strong evidence for improved preservation of donor livers by machine perfusion, longer post-transplant follow-up data are urgently needed in an unselected patient population. We aimed to assess long-term outcomes after transplantation of hypothermic oxygenated machine perfusion (HOPE)-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). In this international, multicentre, observational cohort study, we collected data from adult recipients of HOPE-treated livers transplanted between January 2012 and December 2021. Analyses were stratified by donation after brain death (DBD) and donation after circulatory death (DCD), sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischaemic cholangiopathy (IC). We report on 1,202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low risk (10%), 186 as high risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival rates for DBD and DCD livers were 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (log-rank p = 0.003). Within DBD and DCD strata, death-censored graft survival was similar among risk groups (log-rank p = 0.26, p = 0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE treatment has now reached IDEAL-D stage 4, which further supports its implementation in routine clinical practice. ClinicalTrials.gov Identifier: NCT05520320. This study demonstrates the excellent long-term performance of hypothermic oxygenated machine perfusion (HOPE) treatment of donation after circulatory and donation after brain death liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomised-controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE treatment has now reached the final IDEAL-D stage 4, which further supports its implementation in routine clinical practice.

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These patients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmacologic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period, respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infectious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and protocols of vaccination in SOT adult candidates and recipients.

Mesenchymal stromal cells (MSC) have emerged as a promising therapy to minimize the immunosuppressive regimen or induce tolerance in solid organ transplantation. In this randomized open‐label phase Ib/IIa clinical trial, 20 liver transplant patients were randomly allocated (1:1) to receive a single pre‐transplant intravenous infusion of third‐party bone marrow‐derived MSC or standard of care alone. The primary end‐point was the safety profile of MSC administration during the one‐year follow‐up. Nineteen patients completed the study, and none of those who received MSC experienced infusion‐related complications. The incidence of serious and non‐serious adverse events was similar in the two groups. Circulating Treg/memory Treg and tolerant NK subset of CD56^bright NK cells increased slightly over baseline, albeit not to a statistically significant extent, in MSC‐treated patients but not in the control group. Graft function and survival, as well as histologic parameters and intragraft expression of tolerance‐associated transcripts in 1‐year protocol biopsies were similar in the two groups. In conclusion, pre‐transplant MSC infusion in liver transplant recipients was safe and induced mild positive changes in immunoregulatory T and NK cells in the peripheral blood. This study opens the way for a trial on possible tolerogenic efficacy of MSC in liver transplantation. ClinicalTrials.gov identifier: NCT02260375.

Background and aims: Besides the increased risk of perioperative morbidity, graft failure, and mortality, the majority of PVT are diagnosed at liver transplantation (LT). Improving preoperative management and patient selection may lead to better short-term and long-term outcomes and reduce the risk of a futile LT. The authors aimed to identify predictors of adverse outcomes after LT in patients with nonmalignant portal vein thrombosis (PVT) and improve donor to recipient matching by analyzing the results of the Italian cohort of LT recipients. Methods: Adult patients who underwent LT in Italy between January 2000 and February 2020 diagnosed with PVT pre-LT or at time of LT were considered eligible for inclusion. Based on a survey encompassing all 26 surgeons participating in the study, a binary composite outcome was defined. Patients were classified as having the composite event if at least one of these conditions occurred: operative time more than 600 min, estimated blood loss greater than 5000 ml, more than 20 ICU days, 90 days mortality, 90 days retransplant. Results: Seven hundred fourteen patients were screened and 698 met the inclusion criteria. The analysis reports the results of 568 patients that fulfilled the criteria to enter the composite outcome analysis. Overall, 156 patients (27.5%) developed the composite outcome. PVT stage 3/4 at transplant and need for any surgical correction of PVT are independent predictors of the composite outcome occurrence. When stratified by PVT grade, overall survival at 1-year ranges from 89.0% with PVT grade 0/1 to 67.4% in patients with PVT grade 3/4 at LT (P<0.001). Nevertheless, patients with severe PVT can improve their survival when identified risk factors are not present. Conclusions: Potential LT candidates affected by PVT have a benefit from LT that should be adequately balanced on liver function and type of inflow reconstruction needed to mitigate the incidence of adverse events. Nonetheless, the absence of specific risk factors may improve the outcomes even in patients with PVT grades 3–4.