First-in-human liver transplantation from a centenarian deceased donor after brain death.

Liver transplantation from elderly donors is expanding due to demand for liver grafts, aging of recipients and donors, and introduction of machine perfusion. We report on a liver transplant from a 100-year-old deceased donor after brain death. The liver was transplanted after the use of hypothermic machine perfusion to a 60-year-old recipient with advanced hepatocellular carcinoma undergoing neoadjuvant immunotherapy. Nine months after the transplant, the patient is alive with a functioning graft and no evidence of acute rejection or tumor recurrence.

Liver transplantation with uncontrolled versus controlled DCD donors using normothermic regional perfusion and ex-situ machine perfusion.

In Italy, 20 minutes of continuous, flat-line electrocardiogram are required for death declaration, which significantly increases the risks of donation after circulatory death (DCD) LT. Despite prolonged warm ischemia time, Italian centers reported good outcomes in controlled donation after circulatory death LT by combining normothermic regional and end-ischemic machine perfusion. However, data on uncontrolled DCD (uDCD) LT performed by this approach are lacking. This was a multicenter, retrospective study performed at 3 large-volume centers comparing clinical outcomes of uncontrolled versus controlled DCD LT. The aim of the study was to assess outcomes of sequential normothermic regional perfusion and end-ischemic machine perfusion in uncontrolled DCD liver transplantation (LT). Of 153 DCD donors evaluated during the study period, 40 uDCD and 59 donation after circulatory death grafts were transplanted (utilization rate 52% vs. 78%, p = 0.004). Recipients of uDCD grafts had higher MEAF (4.9 vs. 3.5, p < 0.001) and CCI scores at discharge (24.4 vs. 8.7, p = 0.026), longer ICU stay (5 vs. 4 d, p = 0.047), and a trend toward more severe AKI. At multivariate analysis, 90-day graft loss was associated with recipient BMI and lactate downtrend during normothermic regional perfusion. One-year graft survival was lower in uDCD (75% vs. 90%, p = 0.007) but became comparable when non-liver-related graft losses were treated as censors (77% vs. 90%, p = 0.100). The incidence of ischemic cholangiopathy was 10% in uDCD versus 3% in donation after circulatory death, p = 0.356. uDCD LT with prolonged warm ischemia is feasible by the sequential use of normothermic regional perfusion and end-ischemic machine perfusion. Proper donor and recipient selection are key to achieving good outcomes in this setting.

Recipient hepatectomy technique may affect oncological outcomes of liver transplantation for hepatocellular carcinoma.

To date, caval sparing (CS) and total caval replacement (TCR) for recipient hepatectomy in liver transplantation (LT) have been compared only in terms of surgical morbidity. Nonetheless, the CS technique is inherently associated with an increased manipulation of the native liver and later exclusion of the venous outflow, which may increase the risk of intraoperative shedding of tumor cells when LT is performed for HCC. A multicenter, retrospective study was performed to assess the impact of recipient hepatectomy (CS vs. TCR) on the risk of posttransplant HCC recurrence among 16 European transplant centers that used either TCR or CS recipient hepatectomy as an elective protocol technique. Exclusion criteria comprised cases of non-center-protocol recipient hepatectomy technique, living-donor LT, HCC diagnosis suspected on preoperative imaging but not confirmed at the pathological examination of the explanted liver, HCC in close contact with the IVC, and previous liver resection for HCC. In 2420 patients, CS and TCR approaches were used in 1452 (60%) and 968 (40%) cases, respectively. Group adjustment with inverse probability weighting was performed for high-volume center, recipient age, alcohol abuse, viral hepatitis, Child-Pugh class C, Model for End-Stage Liver Disease score, cold ischemia time, clinical HCC stage within Milan criteria, pre-LT downstaging/bridging therapies, pre-LT alphafetoprotein serum levels, number and size of tumor nodules, microvascular invasion, and complete necrosis of all tumor nodules (matched cohort, TCR, n = 938; CS, n = 935). In a multivariate cause-specific hazard model, CS was associated with a higher risk of HCC recurrence (HR: 1.536, p = 0.007). In conclusion, TCR recipient hepatectomy, compared to the CS approach, may be associated with some protective effect against post-LT tumor recurrence.

Improving outcomes of in situ split liver transplantation in Italy over the last 25 years.

BACKGROUND & AIMS: Split liver transplant(ation) (SLT) is still considered a challenging procedure that is by no means widely accepted. We aimed to present data on 25-year trends in SLT in Italy, and to investigate if, and to what extent, outcomes have improved nationwide during this time. METHODS: The study included all consecutive SLTs performed from May 1993 to December 2019, divided into three consecutive periods: 1993-2005, 2006-2014, and 2015-2019, which match changes in national allocation policies. Primary outcomes were patient and graft survival, and the relative impact of each study period. RESULTS: SLT accounted for 8.9% of all liver transplants performed in Italy. A total of 1,715 in situ split liver grafts were included in the analysis: 868 left lateral segments (LLSs) and 847 extended right grafts (ERGs). A significant improvement in patient and graft survival (p <0.001) was observed with ERGs over the three periods. Predictors of graft survival were cold ischaemia time (CIT) <6 h (p = 0.009), UNOS status 2b (p <0.001), UNOS status 3 (p = 0.009), and transplant centre volumes: 25-50 cases vs. <25 cases (p = 0.003). Patient survival was significantly higher with LLS grafts in period 2 vs. period 1 (p = 0.008). No significant improvement in graft survival was seen over the three periods, where predictors of graft survival were CIT <6 h (p = 0.007), CIT <6 h vs. ≥10 h (p = 0.019), UNOS status 2b (p = 0.038), and UNOS status 3 (p = 0.009). Retransplantation was a risk factor in split liver graft recipients, with significantly worse graft and patient survival for both types of graft (p <0.001). CONCLUSIONS: Our analysis showed Italian SLT outcomes to have improved over the last 25 years. These results could help to dispel reservations regarding the use of this procedure. IMPACT AND IMPLICATIONS: Split liver transplant(ation) (SLT) is still considered a challenging procedure and is by no means widely accepted. This study included all consecutive in situ SLTs performed in Italy from May 1993 to December 2019. With more than 1,700 cases, it is one of the largest series, examining long-term national trends in in situ SLT since its introduction. The data presented indicate that the outcomes of SLT improved during this 25-year period. Improvements are probably due to better recipient selection, refinements in surgical technique, conservative graft-to-recipient matching, and the continuous, yet carefully managed, expansion of donor selection criteria under a strict mandatory split liver allocation policy. These results could help to dispel reservations regarding the use of this procedure.

An extensive evaluation of hepatic markers of damage and regeneration in controlled and uncontrolled donation after circulatory death.

Livers from donations after circulatory death (DCDs) are very sensitive to ischemia/reperfusion injury and thus need careful reconditioning, such as normothermic regional perfusion (NRP). So far, its impact on DCDs has not been thoroughly investigated. This pilot cohort study aimed to explore the NRP impact on liver function by evaluating dynamic changes of circulating markers and hepatic gene expression in 9 uncontrolled DCDs (uDCDs) and 10 controlled DCDs. At NRP start, controlled DCDs had lower plasma levels of inflammatory and liver damage markers, including α-glutathione s-transferase, sorbitol-dehydrogenase, malate dehydrogenase 1, liver-type arginase-1, and keratin-18, but higher levels of osteopontin, sFas, flavin mononucleotide, and succinate than uDCDs. During 4-hour NRP, some damage and inflammatory markers increased in both groups, while IL-6, HGF, and osteopontin increased only in uDCDs. At the NRP end, the tissue expression of early transcriptional regulators, apoptosis, and autophagy mediators was higher in uDCDs than in controlled DCDs. In conclusion, despite initial differences in liver damage biomarkers, the uDCD group was characterized by a major gene expression of regenerative and repair factors after the NRP procedure. Correlative analysis among circulating/tissue biomarkers and the tissue congestion/necrosis degree revealed new potential candidate biomarkers.

Robotic versus laparoscopic liver resections: propensity-matched comparison of two-center experience.

BACKGROUND: The advantages of the robotic approach in minimally invasive liver surgery (MILS) are still debated. This study compares the short-term outcomes between laparoscopic (LLR) and robotic (RLR) liver resections in propensity score matched cohorts. METHODS: Data regarding minimally invasive liver resections in two liver surgery units were retrospectively reviewed. A propensity score matched analysis (1:1 ratio) identified two groups of patients with similar characteristics. Intra- and post-operative outcomes were then compared. The difficulty of MILS was based on the IWATE criteria. RESULTS: Two hundred sixty-nine patients underwent MILS between January 2014 and December 2021 (LLR = 192; RLR = 77). Propensity score matching identified 148 cases (LLR = 74; RLR = 74) consisting of compensated cirrhotic patients (100%) underwent non-anatomic resection of IWATE 1-2 class (90.5%) for a solitary tumor < 5 cm in diameter (93.2%). In such patients, RLRs had shorter operative time (227 vs. 250 min, p = 0.002), shorter Pringle's cumulative time (12 vs. 28 min, p < 0.0001), and less blood loss (137 vs. 209 cc, p = 0.006) vs. LLRs. Conversion rate was nihil (both groups). In RLRs compared to LLRs, R0 rate (93 vs. 96%, p > 0.71) and major morbidity (4.1 vs. 5.4%, p > 0.999) were similar, without post-operative mortality. Hospital stay was shorter in the robotic group (6.2 vs. 6.6, p = 0.0001). CONCLUSION: This study supports the non-inferiority of RLR over LLR. In compensated cirrhotic patients underwent resection of low-to-intermediate difficulty for a solitary nodule < 5 cm, RLR was faster, with less blood loss despite the shorter hilar clamping, and required shorter hospitalization compared to LLR.

The role of sequential normothermic regional perfusion and end-ischemic normothermic machine perfusion in liver transplantation from very extended uncontrolled donation after cardiocirculatory death.

The use of pre-procurement normothermic regional perfusion (NRP) allowed us to implement controlled DCD liver transplantation with results comparable to brain death donors, but the use of uncontrolled DCD is declining due to logistic challenges and the high incidence of post-transplant complications. In Italy, the mandatory stand-off period of 20 min for DCD donors has driven the combined use of NRP and ex-situ machine perfusion with the intent to counterbalance the negative impact of prolonged warm ischemia. Organ viability during NRP is based on duration of warm ischemia, regional perfusion flow, lactate, transaminases values and histology, and those used in Italy are the widest worldwide. However, this evaluation can be difficult, especially when the acute damage is particularly severe. The use of ex-situ NRP could provide a safe organ evaluation. In the period from 06/2020 to 06/2022, all DCD grafts exceeding NRP viability criteria at a single center were eventually evaluated using ex-situ normothermic machine perfusion. Machine perfusion viability criteria were based on lactate clearance, irrespectively to bile production, unless 1-h transaminases perfusate level were not exceeding 5000 IU/L. Three cases of uncontrolled DCD grafts in excess of NRP viability criteria underwent ex-situ graft evaluation. Two matched ex-situ normothermic machine perfusion viability criteria and were successfully transplanted. Both recipients are doing well after 26 and 5 months after surgery with no signs of ischemic cholangiopathy. This experience suggests that the sequential use of NRP and normothermic machine perfusion may further expand the boundaries of organ viability in uncontrolled DCD liver transplantation.

Impact of MELD 30-allocation policy on liver transplant outcomes in Italy.

BACKGROUND & AIMS: In Italy, since August 2014, liver transplant (LT) candidates with model for end-stage liver disease (MELD) scores ≥30 receive national allocation priority. This multicenter cohort study aims to evaluate time on the waiting list, dropout rate, and graft survival before and after introducing the macro-area sharing policy. METHODS: A total of 4,238 patients registered from 2010 to 2018 were enrolled and categorized into an ERA-1 Group (n = 2,013; before August 2014) and an ERA-2 Group (n = 2,225; during and after August 2014). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of receiving a LT or death between the two eras. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss. RESULTS: Patients with MELD ≥30 had a lower median time on the waiting list (4 vs.12 days, p <0.001) and a higher probability of being transplanted (HR 2.27; 95% CI 1.78-2.90; p = 0.001) in ERA-2 compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio 0.56; 95% CI 0.46-0.68; p = 0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high-volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high-volume center and ERA-2, while MELD ≥30 remained related to a higher risk of graft loss. CONCLUSIONS: The national MELD ≥30 priority allocation was associated with improved patient outcomes, although MELD ≥30 was associated with a higher risk of graft loss. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes. CLINICAL TRIAL NUMBER: NCT04530240 LAY SUMMARY: Italy introduced a new policy in 2014 to give national allocation priority to patients with a model for end-stage liver disease (MELD) score ≥30 (i.e. very sick patients). This policy has led to more liver transplants, fewer dropouts, and shorter waiting times for patients with MELD ≥30. However, a higher risk of graft loss still burdens these cases. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes.

Cerium oxide nanoparticles administration during machine perfusion of discarded human livers: A pilot study.

The combined approach of ex situ normothermic machine perfusion (NMP) and nanotechnology represents a strategy to mitigate ischemia/reperfusion injury in liver transplantation (LT). We evaluated the uptake, distribution, and efficacy of antioxidant cerium oxide nanoparticles (nanoceria) during normothermic perfusion of discarded human livers. A total of 9 discarded human liver grafts were randomized in 2 groups and underwent 4 h of NMP: 5 grafts were treated with nanoceria conjugated with albumin (Alb-NC; 50 µg/ml) and compared with 4 untreated grafts. The intracellular uptake of nanoceria was analyzed by electron microscopy (EM) and inductively coupled plasma-mass spectrometry (ICP-MS). The antioxidant activity of Alb-NC was assayed in liver biopsies by glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) assay, telomere length, and 4977-bp common mitochondrial DNA deletion (mtDNA4977 deletion). The cytokine profile was evaluated in perfusate samples. EM and ICP-MS confirmed Alb-NC internalization, rescue of mitochondrial phenotype, decrease of lipid droplet peroxidation, and lipofuscin granules in the treated grafts. Alb-NC exerted an antioxidant activity by increasing GSH levels (percentage change: +94% ± 25%; p = 0.01), SOD (+17% ± 4%; p = 0.02), and CAT activity (51% ± 23%; p = 0.03), reducing the occurrence of mtDNA4977 deletion (-67.2% ± 11%; p = 0.03), but did not affect cytokine release. Alb-NC during ex situ perfusion decreased oxidative stress, upregulating graft antioxidant defense. They could be a tool to improve quality grafts during NMP and represent an antioxidant strategy aimed at protecting the graft against reperfusion injury during LT.

Quality of life in liver transplant recipients during the Corona virus disease 19 pandemic: A multicentre study.

BACKGROUND: Liver transplant recipients require specific clinical and psychosocial attention given their frailty. Main aim of the study was to assess the quality of life after liver transplant during the current pandemic. METHODS: This multicentre study was conducted in clinically stable, liver transplanted patients. Enrollment opened in June and finished in September 2021. Patients completed a survey including lifestyle data, quality of life (Short Form health survey), sport, employment, diet. To examine the correlations, we calculated Pearson coefficients while to compare subgroups, independent samples t-tests and ANOVAs. To detect the predictors of impaired quality of life, we used multivariable logistic regression analysis. RESULTS: We analysed data from 511 patients observing significant associations between quality of life's physical score and both age and adherence to Mediterranean diet (p < .01). A significant negative correlation was observed between mental score and the sedentary activity (p < .05). Female patients scored significantly lower than males in physical and mental score. At multivariate analysis, females were 1.65 times more likely to report impaired physical score than males. Occupation and physical activity presented significant positive relation with quality of life. Adherence to Mediterranean diet was another relevant predictor. Regarding mental score, female patients were 1.78 times more likely to show impaired mental score in comparison with males. Sedentary activity and adherence to Mediterranean diet were further noteworthy predictors. CONCLUSIONS: Females and subjects with sedentary lifestyle or work inactive seem to show the worst quality of life and both physical activity and Mediterranean diet might be helpful to improve it.

Hospital-Based Health Technology Assessment of Machine Perfusion Systems for Human Liver Transplantation.

Based on published data, we have carried out a hospital-based health technology assessment of machine perfusion in adult liver transplantation using cold storage as a comparator, and within the perspective of a national health system-based hospital practice and disease-related group reimbursement policy. A systematic literature review on machine perfusion for adult liver transplantation was conducted exploring the Pubmed, CINAHL, Scopus, Embase, and Cochrane databases. The literature was analyzed with the intent to provide information on 6 dimensions and 19 items of the hospital-based health technology assessment framework derived from previous studies. Out of 705 references, 47 (6.7%) were retained for current analysis. Use of machine perfusion was associated with advantages over cold storage, i.e., a 10%-50% reduced risk for early allograft dysfunction, 7%-15% less ischemia reperfusion injury; 7%-50% fewer ischemic biliary complications, comparable or improved 1-year graft and patient survival, and up to a 50% lower graft discard rate. Hospital stay was not longer, and technical failures were anecdotal. Information on costs of machine perfusion is limited, but this technology is projected to increase hospital costs while cost-effectiveness analysis requires data over the transplant patient lifetime. No hospital-based health technology assessment study on machine perfusion in liver transplantation was previously conducted. From the hospital perspective, there is evidence of the clinical advantages of this novel technology, but strategies to counterbalance the increased costs of liver transplantation are urgently needed. Further studies should focus on the ethical, social, and organizational issues related to machine perfusion.

Implementing a robotic liver resection program does not always require prior laparoscopic experience.

BACKGROUND: Preliminary experience in laparoscopic liver surgery is usually suggested prior to implementation of a robotic liver resection program. METHODS: This was a retrospective cohort analysis of patients undergoing robotic (RLR) versus laparoscopic liver resection (LLR) for hepatocellular carcinoma at a center with concomitant initiation of robotic and laparoscopic programs RESULTS: A total of 92 consecutive patients operated on between May 2014 and February 2019 were included: 40 RLR versus 52 LLR. Median age (69 vs. 67; p = 0.74), male sex (62.5% vs. 59.6%; p = 0.96), incidence of chronic liver disease (97.5% vs.98.1%; p = 0.85), median model for end-stage liver disease (MELD) score (8 vs. 9; p = 0.92), and median largest nodule size (22 vs. 24 mm) were similar between RLR and LLR. In the LLR group, there was a numerically higher incidence of nodules located in segment 4 (20.0% vs. 16.6%; p = 0.79); a numerically higher use of Pringle's maneuver (32.7% vs. 20%; p = 0.23), and a shorter duration of surgery (median of 165.5 vs. 217.5 min; p = 0.04). Incidence of complications (25% vs.32.7%; p = 0.49), blood transfusions (2.5% vs.9.6%; p = 0.21), and median length of stay (6 vs. 5; p = 0.54) were similar between RLR and LLR. The overall (OS) and recurrence-free (RFS) survival rates at 1 and 5 years were 100 and 79 and 95 and 26% for RLR versus 96.2 and 76.9 and 84.6 and 26.9% for LLR (log-rank p = 0.65 for OS and 0.72 for RFS). CONCLUSIONS: Based on our results, concurrent implementation of a robotic and laparoscopic liver resection program appears feasible and safe, and is associated with similar oncologic long-term outcomes.

A new ex-situ machine perfusion device. A preliminary evaluation using a model of donors after circulatory death pig livers.

We herein describe a new ex-situ machine perfusion device as a "technology spotlight" using a model of donors after circulatory death liver grafts procured from slaughterhouse pigs. Fourteen pig liver grafts were included. The device allowed stable perfusion in both hypothermic (n = 6) and normothermic (n = 8) conditions and no technical failure was observed. During perfusion, perfusate and bile samples were collected to assess liver metabolism and viability. An integrated adsorption device showed efficient removal of inflammatory cytokines during treatment. This preliminary experience represents the starting point for further investigations on the potential clinical benefits of cytokines and other inflammatory mediators adsorption during machine perfusion.

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

BACKGROUND: Organs from donation after circulatory death (DCD) are increasingly used for liver transplantation, due to the persisting organ shortage and waiting list mortality. However, the use of DCD grafts is still limited by the inferior graft survival rate and the increased risk of primary non-function and biliary complications when compared to brain death donors' grafts. METHODS: Abdominal normothermic regional perfusion with extracorporeal membrane oxygenation (ECMO) is an in situ preservation strategy. which may mitigate ischemia-reperfusion injuries. and has been proposed to restore blood perfusion after the determination of death thus optimizing liver function before implantation. RESULTS: In this systematic review, we highlighted the clinical evidence supporting the use of normothermic regional perfusion in DCD liver underlying the pathophysiological mechanisms, and technical, logistic, and regulatory aspects. CONCLUSIONS: Despite the lack of properly designed, prospective, randomized trials, the current available data suggest beneficial effects of normothermic regional perfusion on clinical outcomes after liver transplantation.

Predictors of solid extra-hepatic non-skin cancer in liver transplant recipients and analysis of survival: A long-term follow-up study.

INTRODUCTION AND OBJECTIVES: De novo malignancies represent an important cause of death for liver transplant recipients. Our aim was to analyze predictors of extra-hepatic non-skin cancer (ESNSC) and the impact of ESNSC on the long-term outcome. PATIENTS: We examined data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics with a retrospective observational cohort study. Cox Regression was performed to identify predictors of ESNSC. A 1:2 cohort sub-study was developed to analyze the impact of ESNSC on 10-year survival. RESULTS: We analyzed data from 367 subjects (median follow-up: 15 years). Patients with ESNSC (n = 47) more often developed post-LT diabetes mellitus (DM) (57.4% versus 35,9%, p = 0.004). At multivariate analysis, post-LT DM independently predicted ESNSC (HR 1.929, CI 1.029-3.616, p = 0.040). Recipients with ESNSC showed a lower 10-year survival than matched controls (46,8% versus 68,1%, p = 0.023). CONCLUSIONS: Post-LT DM seems to be a relevant risk factor for post-LT ESNSC. ESNSC could have a noteworthy impact on the long-term survival of LT recipients.

Everolimus versus mycophenolate mofetil in liver transplantation: every improvement in renal function matters.

The current edition of the journal features a Spanish, nationwide, multi-institutional study by Gomez Bravo MA et al. exploring the advantages of everolimus (EVR)-facilitated tacrolimus (TAC) minimization versus TAC in combination with mycophenolate mofetil (MMF) after liver transplantation (LT).

Viability Criteria during Liver Ex-Situ Normothermic and Hypothermic Perfusion.

With the increased use of extended-criteria donors, machine perfusion became a beneficial alternative to cold storage in preservation strategy for donor livers with the intent to expand donor pool. Both normothermic and hypothermic approach achieved good results in terms of mid- and long-term outcome in liver transplantation. Many markers and molecules have been proposed for the assessment of liver, but no definitive criteria for graft viability have been validated in large clinical trials and key parameters during perfusion still require optimization.In this review, we address the current literature of viability criteria during normothermic and hypothermic machine perfusion and discuss about future steps and evolution of these technologies.

COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study.

OBJECTIVE: Explore the impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course. DESIGN: Data from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and were analysed. RESULTS: From 21 February to 20 November 2020, 136 adult cases with laboratory-confirmed SARS-CoV-2 infection from 33 centres in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32.7%) patients died after a median of 18 (10-30) days, with respiratory failure being the major cause (33/37, 89.2%). The 60-day mortality risk did not significantly change between first (35.3%, 95% CI 23.9% to 50.0%) and second (26.0%, 95% CI 16.2% to 40.2%) waves. Multivariable Cox regression analysis showed Laboratory Model for End-stage Liver Disease (Lab-MELD) score of ≥15 (Model for End-stage Liver Disease (MELD) score 15-19, HR 5.46, 95% CI 1.81 to 16.50; MELD score≥20, HR 5.24, 95% CI 1.77 to 15.55) and dyspnoea on presentation (HR 3.89, 95% CI 2.02 to 7.51) being the two negative independent factors for mortality. Twenty-six patients underwent an LT after a median time of 78.5 (IQR 44-102) days, and 25 (96%) were alive after a median follow-up of 118 days (IQR 31-170). CONCLUSIONS: Increased mortality in LT candidates with COVID-19 (32.7%), reaching 45% in those with decompensated cirrhosis (DC) and Lab-MELD score of ≥15, was observed, with no significant difference between first and second waves of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with DC supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).

Sequential Use of Normothermic Regional and Ex Situ Machine Perfusion in Donation After Circulatory Death Liver Transplant.

In Italy, 20 minutes of a continuous flat line on an electrocardiogram are required for declaration of death. In the setting of donation after circulatory death (DCD), prolonged warm ischemia time prompted the introduction of abdominal normothermic regional perfusion (NRP) followed by postprocurement ex situ machine perfusion (MP). This is a retrospective review of DCD liver transplantations (LTs) performed at 2 centers using sequential NRP and ex situ MP. From January 2018 to April 2019, 34 DCD donors were evaluated. Three (8.8%) were discarded before NRP, and 11 (32.4%) were discarded based on NRP parameters (n = 1, 3.0%), liver macroscopic appearance at procurement and/or biopsy results (n = 9, 26.5%), or severe macroangiopathy at back-table evaluation (n = 1, 3.0%). A total of 20 grafts (58.8%; 11 uncontrolled DCDs, 9 controlled DCDs) were considered eligible for LT, procured and perfused ex situ (9 normothermic and 11 dual hypothermic MPs). In total, 18 (52.9%; 11 uncontrolled) livers were eventually transplanted. Median (interquartile range) no-flow time was 32.5 (30-39) minutes, whereas median functional warm ischemia time was 52.5 (47-74) minutes (controlled DCD), and median low-flow time was 112 minutes (105-129 minutes; uncontrolled DCD). There was no primary nonfunction, while postreperfusion syndrome occurred in 8 (44%) recipients. Early allograft dysfunction happened in 5 (28%) patients, while acute kidney injury occurred in 5 (28%). After a median follow-up of 15.1 (9.5-22.3) months, 1 case of ischemic-type biliary lesions and 1 patient death were reported. DCD LT is feasible even with the 20-minute no-touch rule. Strict NRP and ex situ MP selection criteria are needed to optimize postoperative results.

The Role of Salvage Transplantation in Patients Initially Treated With Open Versus Minimally Invasive Liver Surgery: An Intention-to-Treat Analysis.

Despite gaining wide consensus in the management of hepatocellular carcinoma (HCC), minimally invasive liver surgery (MILS) has been poorly investigated for its role in the setting of salvage liver transplantation (SLT). A multicenter retrospective analysis was carried out in 6 Italian centers on 211 patients with HCC who were initially resected with open (n = 167) versus MILS (n = 44) and eventually wait-listed for SLT. The secondary endpoint was identification of risk factors for posttransplant death and tumor recurrence. The enrolled patients included 211 HCC patients resected with open surgery (n = 167) versus MILS (n = 44) and wait-listed for SLT between January 2007 and December 2017. We analyzed the intention-to-treat survival of these patients. MILS was the most important protective factor for the composite risk of delisting, posttransplant patient death, and HCC recurrence (OR, 0.26; 95% confidence interval [CI], 0.11-0.63; P = 0.003). MILS was also the only independent protective factor for the risk of post-SLT patient death (OR, 0.29; 95% CI, 0.09-0.93; P = 0.04). After propensity score matching, MILS was the only independent protective factor against the risk of delisting, posttransplant death, and HCC recurrence (OR, 0.22; 95% CI, 0.07-0.75; P = 0.02). On the basis of the current analysis, MILS seems protective over open surgery for the risk of delisting, posttransplant patient death, and tumor recurrence. Larger prospective studies balancing liver function and tumor stage are strongly favored to better clarify the beneficial effect of MILS for HCC patients eventually referred to SLT.