A randomized trial of normothermic preservation in liver transplantation.

Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality.

Focusing on Ischemic Reperfusion Injury in the New Era of Dynamic Machine Perfusion in Liver Transplantation.

Liver transplantation is the most effective treatment for end-stage liver disease. Transplant indications have been progressively increasing, with a huge discrepancy between the supply and demand of optimal organs. In this context, the use of extended criteria donor grafts has gained importance, even though these grafts are more susceptible to ischemic reperfusion injury (IRI). Hepatic IRI is an inherent and inevitable consequence of all liver transplants; it involves ischemia-mediated cellular damage exacerbated upon reperfusion and its severity directly affects graft function and post-transplant complications. Strategies for organ preservation have been constantly improving since they first emerged. The current gold standard for preservation is perfusion solutions and static cold storage. However, novel approaches that allow extended preservation times, organ evaluation, and their treatment, which could increase the number of viable organs for transplantation, are currently under investigation. This review discusses the mechanisms associated with IRI, describes existing strategies for liver preservation, and emphasizes novel developments and challenges for effective organ preservation and optimization.

Validation of the Back-table Graft Arterial Anastomosis between the Splenic Artery and Superior Mesenteric Artery: Arterial Complications after a 21-year Single-center Experience of Pancreas Transplantation.

OBJECTIVE: To determine the role of the arterial splenomesenteric anastomosis (ASMA) vascular reconstruction technique in terms of arterial vascular complications in pancreas transplant (PT) recipients. SUMMARY BACKGROUND DATA: The ASMA technique was first described in 1992 by Hospital Clínic Barcelona group. Regardless that the iliac Y-graft technique is the most frequently used worldwide, evidence of arterial complications and implications of using a different back-table reconstruction is conspicuously absent in the literature. METHODS: Descriptive review of 407 PTs performed at a single center (1999-2019) by analyzing the type of arterial reconstruction technique, focusing on ASMA. The endpoints were the management of arterial complications and long-term patient and graft survival. RESULTS: ASMA was performed in 376 cases (92.4%) and a Y-graft in 31 cases (7.6%). A total of 34 arterial complications (8.3%) were diagnosed. In the ASMA group (n=30, 7.9%) they comprised: 15 acute thrombosis; 4 stenosis; 1 pseudoaneurysm and 10 diverse chronic arterial complications while in the Y-graft group (n=4, 12.9%) 3 acute thrombosis and 1 chronic artery-duodenal fistula occurred. Graft salvage was achieved in 16 patients (53.3%) from the ASMA group and in 2 (50%) from the Y-graft. After a median follow-up of 129.2 (IQR 25-75%, 77.2 -182) months the overall graft and patient survival for the whole cohort at 1, 5, and 10 years was 86.7%, 79.5%, 70.5%, and 98.5%, 95.3%, 92.5%, respectively. CONCLUSIONS: The ASMA proves to be a safe and more easily reproducible technique and should therefore be considered for first-line back-table reconstruction in the PT population.

In situ normothermic regional perfusion versus ex situ normothermic machine perfusion in liver transplantation from donation after circulatory death.

In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p = 0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p = 0.17), UK-Donation After Circulatory Death risk score (5 vs. 5 points; p = 0.38), and laboratory Model for End-Stage Liver Disease scores (12 vs. 12 points; p = 0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p = 0.13), and 30-day graft loss (4.4% vs. 8.8%; p = 0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC-censored 2-year graft and patient survival rates were 91.5% versus 88.2% (p = 0.52) and 97.9% versus 94.1% (p = 0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial.

Current Trends in Organ Preservation Solutions for Pancreas Transplantation: A Single-Center Retrospective Study.

Due to the high vulnerability of the pancreas to ischemia-reperfusion injury, choices regarding preservation solution markedly affect pancreas transplant success. A retrospective single-center analysis of 380 pancreas transplants (2000-2019) was performed to correlate current preservation solutions with transplant outcomes. Early graft failure requiring transplantectomy within 30 days post-transplant occurred in 7.5% for University of Wisconsin (UW) group (n = 267), 10.8% of Celsior (CS) group (n = 83), 28.5% of Histidine-Tryptophan-Ketoglutarate (HTK) group (n = 7), and none for Institut Georges Lopez-1 (IGL-1) group (n = 23). The most common causes of technical failures in this cohort included abdominal hemorrhage (8.4%); graft pancreatitis (3.7%); fluid collections (2.6%); intestinal complications (6.6%); and vascular thrombosis (20.5%). Although IGL-1 solution provided lower surgical complication rates, no significant differences were found between studied groups. Nevertheless, HTK solution was associated with elevated pancreatitis rates. The best graft survival was achieved at 1 year using UW and IGL-1, and at 3 and 5 years using IGL-1 (p = 0.017). There were no significant differences in patient survival after a median follow-up of 118.4 months. In this setting therefore, IGL-1 solution appears promising for perfusion and organ preservation in clinical pancreas transplantation, compared to other commonly used solutions.

Limited tumour progression beyond Milan criteria while on the waiting list does not result in unacceptable impairment of survival.

BACKGROUND & AIMS: Defining optimum management of patients progressing beyond Milan criteria on the waiting list is a controversial topic. Our aim was to determine whether the policy of allowing a limited progression beyond enlistment criteria permits acceptable post-transplant outcomes in terms of survival and recurrence. METHODS: Patients with hepatocellular carcinoma included on the waiting list for orthotopic liver transplantation (OLT) between January 1989 and December 2016 were analysed. Tumour features were assessed at inclusion on the waiting list, before OLT and at explant pathology. Patients were retained on the waiting list despite exceeding enlistment criteria if not presenting with macrovascular invasion, extrahepatic spread or cancer-related symptoms. RESULTS: A total of 495 patients constituted the target population. Comparison between the Milan-in (n = 434) and Milan-out (n = 61) groups showed statistically significant differences in: largest tumour size; BCLC stage; patients treated before OLT; alpha-fetoprotein, and time on the waiting list. Milan-out patients showed a significantly higher number of poorly differentiated nodules, satellitosis and microscopic vascular invasion. The 1-, 3-, 5- and 10-year survival rate was 89.6%, 82.5%, 75%, and 55.5%, vs. 83.6%, 70.5%, 65.5%, and 53.9% for Milan-in/Milan-out patients, respectively. Recurrence rates at 1, 3, 5 and 10 years were 1.2%, 3.3%, 5.5%, and 10.8% vs. 7.1% 14.5%, 23%, and 23% for Milan-in and Milan-out patients, respectively (p <0.01). CONCLUSION: This study shows that although limited tumour progression without reaching major adverse predictors (vascular invasion, extrahepatic spread, cancer symptoms) has an expected impact on recurrence rate, overall survival remains above the minimum proposed benchmark of 65% at 5 years. The clinically relevant increase in tumour recurrence must be considered when analysing the benefit of this approach in the face of limited organ supply. LAY SUMMARY: When considering orthotopic liver transplantation for patients with hepatocellular carcinoma, optimum results are achieved when transplanting patients within the Milan criteria. However, the most appropriate strategy for patients who progress beyond these criteria while on the waiting list is still unclear. Herein, we show that transplantation is associated with acceptable overall survival in select patients who progress beyond the Milan criteria, although recurrence rates were notably higher. Therefore, the assessment of transplantation viability in these patients must consider the availability of organs and the impact on other patient categories.

Outcomes From Brain Death Donors With Previous Cardiac Arrest Accepted for Pancreas Transplantation: A Single-center Retrospective Analysis.

OBJECTIVE: The aim of the study was to evaluate the effect of cardiac arrest time (CAT) in donors after brain death (DBD) donors on pancreas transplant outcome. SUMMARY OF BACKGROUND DATA: Results from donors after circulatory death report good outcomes despite warm ischemia times up to 57 minutes. Previous cardiac arrest in DBD has been addressed as a potential risk factor, but duration of the CAT has never been evaluated. METHODS: We conducted a retrospective analysis including 342 pancreas transplants performed at our center from 2000 to 2016, and evaluated the effect of previous cardiac arrest in DBD (caDBD) on pancreas transplant outcomes. RESULTS: A total of 49 (14.3%) caDBD were accepted for transplantation [median CAT of 5.0 min (IQR 2.5-15.0)]. Anoxic encephalopathy was most frequent and P-PASS higher (16.9 vs 15.6) in caDBD group when compared with other DBD. No differences were found in all other characteristics evaluated.Graft survival was similar between both groups, as was the incidence of early graft failure (EGF). CAT increased the risk for EGF [OR 1.09 (95% CI, 1.01-1.17)], and the duration of CPR discriminated for EGF [AUC of 0.86 (95% CI, 0.74-0.98)], with a sensitivity and specificity of 100% and 75% at a cutoff of 15 minutes. When evaluated separately, caDBD >15 min increased over 5 times the risk for EGF [HR 5.80 (95% CI, 1.82-18.56); P = 0.003], and these presented fewer days on the ICU (1.0 vs 3.0 d). CONCLUSION: CaDBD donors are suitable for routine pancreas transplantation without increasing EGF risk, and in those with longer CAT it may be prudent to postpone donation a few days to allow a thorough evaluation of organ damage following cardiac arrest.

Bespoken Nanoceria: An Effective Treatment in Experimental Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Despite the availability of new-generation drugs, hepatocellular carcinoma (HCC) is still the third most frequent cause of cancer-related deaths worldwide. Cerium oxide nanoparticles (CeO2 NPs) have emerged as an antioxidant agent in experimental liver disease because of their antioxidant, anti-inflammatory, and antisteatotic properties. In the present study, we aimed to elucidate the potential of CeO2 NPs as therapeutic agents in HCC. APPROACH AND RESULTS: HCC was induced in 110 Wistar rats by intraperitoneal administration of diethylnitrosamine for 16 weeks. Animals were treated with vehicle or CeO2 NPs at weeks 16 and 17. At the eighteenth week, nanoceria biodistribution was assessed by mass spectrometry (MS). The effect of CeO2 NPs on tumor progression and animal survival was investigated. Hepatic tissue MS-based phosphoproteomics as well as analysis of principal lipid components were performed. The intracellular uptake of CeO2 NPs by human ex vivo perfused livers and human hepatocytes was analyzed. Nanoceria was mainly accumulated in the liver, where it reduced macrophage infiltration and inflammatory gene expression. Nanoceria treatment increased liver apoptotic activity, while proliferation was attenuated. Phosphoproteomic analysis revealed that CeO2 NPs affected the phosphorylation of proteins mainly related to cell adhesion and RNA splicing. CeO2 NPs decreased phosphatidylcholine-derived arachidonic acid and reverted the HCC-induced increase of linoleic acid in several lipid components. Furthermore, CeO2 NPs reduced serum alpha-protein levels and improved the survival of HCC rats. Nanoceria uptake by ex vivo perfused human livers and in vitro human hepatocytes was also demonstrated. CONCLUSIONS: These data indicate that CeO2 NPs partially revert the cellular mechanisms involved in tumor progression and significantly increase survival in HCC rats, suggesting that they could be effective in patients with HCC.

Early intestinal complications following pancreas transplantation: lessons learned from over 300 cases - a retrospective single-center study.

Enteric complications remain a major cause of morbidity in the post-transplant period of pancreas transplantation despite improvements surgical technique. The aim of this single-center study was to analyze retrospectively the early intestinal complications and their potential relation with vascular events. From 2000 to 2016, 337 pancreas transplants were performed with systemic venous drainage. For exocrine secretion, intestinal drainage was done with hand-sewn anastomosis duodenojejunostomy. Twenty-three patients (6.8%) had early intestinal complications. Median age was 39 years (male: 65.2%). Median cold ischemia time was 11 h [IQR: 9-12.4]. Intestinal complications were intestinal obstruction (n = 7); paralytic ileus (n = 5); intestinal fistula without anastomotic dehiscence (n = 3); ischemic graft duodenum (n = 3); dehiscence of duodenojejunostomy (n = 4); and anastomotic dehiscence in jejunum after pancreas transplantectomy (n = 1). Eighteen cases required relaparotomy: adhesiolysis (n = 6); repeated laparotomy without findings (n = 1); transplantectomy (n = 6); primary leak closure (n = 3); re-positioning of the graft (n = 1); and intestinal resection (n = 1). Of the intestinal complications, 4 were associated with vascular thrombosis, resulting in two pancreatic graft losses. Enteric drainage with duodenum-jejunum anastomosis is safe and feasible, with a low rate of intra-abdominal complications. Vascular thrombosis associated with intestinal complications presents a risk factor for the viability of pancreatic grafts, so prevention and early detection is vital.

Missing colorectal liver metastases: the surgical challenge.

BACKGROUND: New chemotherapy schemes have allowed for a better radiological response of unresectable colorectal liver metastases, leading to an interesting scenario known as a complete radiological response. The aim of this study was to review the current management of missing liver metastases (MLM) from the liver surgeon's point of view. METHODS: A systematic search was conducted on all publications of PubMed and Embase between 2003 and 2018. Meta-analysis was performed on MLM resected/unresected. Residual tumor or regrowth and relapse-free survival were used as evaluation indices. RESULTS: After literature search, 18 original articles were included for analysis. The predictive factors for MLM are type and duration of chemotherapy and size and number of lesions. Magnetic resonance is the most sensitive preoperative technique. Regarding clinical management, liver surgery is deemed the fundamental pillar in the therapeutic strategy of these patients. Meta-analysis due to data heterogeneity was inconclusive. CONCLUSIONS: Depending on the clinical context, MLM monitoring appears to be a valid therapeutic alternative. Nevertheless, prospective randomized clinical studies are needed.

Clinical impact of preoperative tumour contact with superior mesenteric-portal vein in patients with resectable pancreatic head cancer.

INTRODUCTION: The NCCN classification of resectability in pancreatic head cancer does not consider preoperative radiological tumour ≤ 180° contact with portal vein/superior mesenteric vein (PV/SMV) as a negative prognostic feature. The aim of this study is to evaluate whether this factor is associated with higher rate of incomplete resection and poorer survival. METHODS: All patients considered for pancreatic resection between 2012 and 2017 at two Spanish referral centres were included. Patients with borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC) according to NCCN classification were excluded. Preoperative CT scans were reviewed by dedicated radiologists to identify radiologic tumour contact with PV/SMV. RESULTS: Out of 302, 71 patients were finally included in this study. Twenty-two (31%) patients showed tumour-PV/SMV contact (group 1) and 49 (69%) did not show any contact (group 2). Patients in group 1 showed a statistically significantly higher rate of R1 and R1-direct margins compared with group 2 (95 vs 28% and 77 vs 10%) and lower median survival (24 vs 41 months, p = 0.02). Preoperative contact with PV/SMV, lymph node metastases, R1-direct margin and NO adjuvant chemotherapy were significantly associated with disease-specific survival at multivariate analysis. CONCLUSION: Preoperative radiological tumour contact with PV/SMV in patients with NCCN resectable PDAC is associated with high rate of pathologic positive margins following surgery and poorer survival.

Liver and kidney transplantation in polycystic liver and kidney disease. / Trasplante hepático y renal en la enfermedad poliquística hepatorrenal.

OBJECTIVE: To evaluate the results of isolated liver and combined liver and kidney transplantation in a retrospective series of 32 patients with hepatorenal liver and kidney disease. MATERIALS AND METHODS: A retrospective observational study that enrolled patients with polycystic liver disease (PLD) and polycystic liver and kidney disease (PLKD) who were evaluated for transplantation between January 1999 and December 2019 at Hospital Clínic de Barcelona [Clinical Hospital of Barcelona]. RESULTS: We included a total of 53 patients enrolled, 32 (60.3%) had indication for transplantation, of which 12 received a single liver transplant and 20 received a double liver and kidney transplant. The mean age was 52 years and 83.9% of the recipients were women. The main indication for liver transplantation was disabling symptomatic hepatomegaly (93.5%). Among the postoperative complications, in the combined liver and kidney transplant group, hepatic artery thrombosis in one case and renal artery thrombosis in other were detected. In both groups there was one case of inferior vena cava lesion. Three patients presented acute cellular rejection responding to corticosteroids and one presented humoral rejection which was treated with plasmapheresis. During the follow-up period of 80 (27-121) months, the liver transplant survival rate was 100% and the kidney transplant survival rate was 90%. Two patients in the combined liver and kidney transplant group died (one due to cardiovascular causes and the other due to intestinal adenocarcinoma). CONCLUSIONS: Isolated liver transplantation or combined liver and kidney transplantation in selected patients with polycystic disease yields excellent results, with few complications, very good transplant survival and excellent patient survival (93.8%).

Influence of donor and recipient gender on liver transplantation outcomes in Europe.

BACKGROUND & AIMS: The impact of gender and donor/recipient gender mismatch on LT outcomes is controversial. The aim of this study was to compare outcomes of LT in Europe, using the ELTR database, between male and female recipients, including donor/recipient gender mismatch. METHODS: Recipient, donor and transplant characteristics were compared between male and female patients. Patient survival was compared between groups, and the impact of donor/recipient gender matching as well as donor and recipient anthropometric characteristics were evaluated as potential risk factors for post-LT death/graft loss. RESULTS: A total of 46,334 LT patients were evaluated (70.5% men and 29.5% women). Ten-year survival rate was significantly higher in female than in male recipients (66% vs 59%, P < .0001). At multivariate analysis, adjusted for indication to LT and type of graft, donor/recipient gender mismatch (HR 1.12, 95% CI 1.04-1.2; P = .003), donor age > 60 years (HR 1.09, 95% CI 1.01-1.18; P = .027) and recipient age (HR 1.02, 95% CI 1.1-1.02; P < .0001) were significantly associated with post-LT lower survival rate in men. Conversely in female recipients, donor BMI > 30 (HR 1.32, 95% CI 1.09-1.6; P = .005), donor age > 60 years (HR 1.15, 95% CI 1.01-1.32; P = .027) and recipient age (HR 1.02, 95% CI 1.01-1.02; P < .0001) were significantly associated with lower post-LT survival rate. CONCLUSIONS: Donor/recipient gender mismatch in male recipients and the use of obese donor in female recipients are associated with reduced survival after LT. Therefore, the incorporation of donor and recipient anthropometric quantities in the allocation process should be a matter of further studies, as their matching can significantly influence long-term outcomes.

Intention-to-treat curative liver resection in patients with "very early" intrahepatic cholangiocarcinoma.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is a rare type of liver cancer. "Very early" ICC, defined as a solitary lesion of ≤ 2 cm in diameter, appears to have a favorable outcome. PURPOSE: This study aimed to assess the outcome of patients with "very early" ICC treated with curative surgical resection in an intention-to-treat analysis. METHODS: All patients with ICC undergoing surgical resection at the Hospital Clínic of Barcelona (Spain) between April 2000 and December 2018 were reviewed, and those with evident "very early" ICC in preoperative imaging studies were selected. Results of histopathologic examination of the surgical specimen, postoperative complications, recurrence, and survival were assessed. RESULTS: Of the 89 patients operated for ICC during the study period, 7 (7.9%) met the "very early" criteria at preoperative imaging. Two (TNM 7th) and four (TNM 8th) patients were classified as stage I, following histological examination of their resected specimens. One patient presented with postoperative morbidity (grade II Clavien-Dindo). The median (IQR) hospital stay was 5 days (3-7). After a median follow-up of 23 months (IQR 11.9-80.6), recurrence was diagnosed in one case at 8.3 months after surgery. The overall survival at 1, 3, and 5 years was 85.7%, 68.6%, and 68.6%, respectively. CONCLUSION: Intention-to-treat curative surgery in "very early" ICC is associated with good results in terms of survival and recurrence. However, most patients presented more advanced stages in the definitive pathological analysis, associated with a lower survival. Future prospective multicenter studies are required to validate these encouraging data.

The prognostic role of hepatic venous pressure gradient in cirrhotic patients undergoing elective extrahepatic surgery.

BACKGROUND & AIMS: Surgery in cirrhosis is associated with a high morbidity and mortality. Retrospectively reported prognostic factors include emergency procedures, liver function (MELD/Child-Pugh scores) and portal hypertension (assessed by indirect markers). This study assessed the prognostic role of hepatic venous pressure gradient (HVPG) and other variables in elective extrahepatic surgery in patients with cirrhosis. METHODS: A total of 140 patients with cirrhosis (Child-Pugh A/B/C: 59/37/4%), who were due to have elective extrahepatic surgery (121 abdominal; 9 cardiovascular/thoracic; 10 orthopedic and others), were prospectively included in 4 centers (2002-2011). Hepatic and systemic hemodynamics (HVPG, indocyanine green clearance, pulmonary artery catheterization) were assessed prior to surgery, and clinical and laboratory data were collected. Patients were followed-up for 1 year and mortality, transplantation, morbidity and post-surgical decompensation were studied. RESULTS: Ninety-day and 1-year mortality rates were 8% and 17%, respectively. Variables independently associated with 1-year mortality were ASA class (American Society of Anesthesiologists), high-risk surgery (defined as open abdominal and cardiovascular/thoracic) and HVPG. These variables closely predicted 90-, 180- and 365-day mortality (C-statistic >0.8). HVPG values >16 mmHg were independently associated with mortality and values ≥20 mmHg identified a subgroup at very high risk of death (44%). Twenty-four patients presented persistent or de novo decompensation at 3 months. Low body mass index, Child-Pugh class and high-risk surgery were associated with death or decompensation. No patient with HVPG <10 mmHg or indocyanine green clearance >0.63 developed decompensation. CONCLUSIONS: ASA class, HVPG and high-risk surgery were prognostic factors of 1-year mortality in cirrhotic patients undergoing elective extrahepatic surgery. HVPG values >16 mmHg, especially ≥20 mmHg, were associated with a high risk of post-surgical mortality. LAY SUMMARY: The hepatic venous pressure gradient is associated with outcomes in patients with cirrhosis undergoing elective extrahepatic surgery. It enables a better stratification of risk in these patients and provides the foundations for potential interventions to improve post-surgical outcomes.

Normothermic regional perfusion vs. super-rapid recovery in controlled donation after circulatory death liver transplantation.

BACKGROUND & AIMS: Although there is increasing interest in its use, definitive evidence demonstrating a benefit for postmortem normothermic regional perfusion (NRP) in controlled donation after circulatory death (cDCD) liver transplantation is lacking. The aim of this study was to compare results of cDCD liver transplants performed with postmortem NRP vs. super-rapid recovery (SRR), the current standard for cDCD. METHODS: This was an observational cohort study including all cDCD liver transplants performed in Spain between June 2012 and December 2016, with follow-up ending in December 2017. Each donor hospital determined whether organ recovery was performed using NRP or SRR. The propensity scores technique based on the inverse probability of treatment weighting (IPTW) was used to balance covariates across study groups; logistic and Cox regression models were used for binary and time-to-event outcomes. RESULTS: During the study period, there were 95 cDCD liver transplants performed with postmortem NRP and 117 with SRR. The median donor age was 56 years (interquartile range 45-65 years). After IPTW analysis, baseline covariates were balanced, with all absolute standardised differences <0.15. IPTW-adjusted risks were significantly improved among NRP livers for overall biliary complications (odds ratio 0.14; 95% CI 0.06-0.35, p <0.001), ischaemic type biliary lesions (odds ratio 0.11; 95% CI 0.02-0.57; p = 0.008), and graft loss (hazard ratio 0.39; 95% CI 0.20-0.78; p = 0.008). CONCLUSIONS: The use of postmortem NRP in cDCD liver transplantation appears to reduce postoperative biliary complications, ischaemic type biliary lesions and graft loss, and allows for the transplantation of livers even from cDCD donors of advanced age. LAY SUMMARY: This is a propensity-matched nationwide observational cohort study performed using livers recovered from donors undergoing cardiac arrest provoked by the intentional withdrawal of life support (controlled donation after circulatory death, cDCD). Approximately half of the livers were recovered after a period of postmortem in situ normothermic regional perfusion, which restored warm oxygenated blood to the abdominal organs, whereas the remainder were recovered after rapid preservation with a cold solution. The study results suggest that the use of postmortem normothermic regional perfusion helps reduce rates of post-transplant biliary complications and graft loss and allows for the successful transplantation of livers from older cDCD donors.

Evolution Under Normothermic Machine Perfusion of Type 2 Donation After Cardiac Death Livers Discarded as Nontransplantable.

BACKGROUND: Type 2 donation after cardiac death (DCD) represents an underused source of grafts for liver transplantation. In our center, normothermic regional perfusion and strict selection criteria have led to acceptable postoperative results after transplanting type 2 DCD livers. However, many of these grafts are still discarded before transplantation. We believe that the suitability of these organs may be improved by adding normothermic machine perfusion (NMP) to our current procedure. MATERIALS AND METHODS: A total of 5 type 2 DCD livers discarded for transplantation were submitted to normothermic regional perfusion and 12 h of NMP. The macroscopic aspect of the liver, vascular and bile flows, and pH were continuously monitored. Serial perfusate analyses and liver biopsies were performed. After NMP, the microscopic appearance of the liver parenchyma and the bile ducts was analyzed. RESULTS: All the grafts showed hemodynamic stability during the NMP. The alanine aminotransferase peak during NMP correlated with the warm ischemia time (Pearson correlation of 0.933, p 0.021). After an initial period of acidosis, the grafts were generally able to spontaneously correct pH and lactate levels without the need for additional bicarbonate. Livers with favorable bile duct histology generally started bile production earlier and registered higher bile flows. CONCLUSIONS: NMP represents a feasible procedure for use with type 2 DCD livers. The pH and lactate correction and the bile flows appear to be significant factors associated with graft viability. However, these favorable results should be confirmed in a clinical transplant setting.

Left-liver Adult-to-Adult Living Donor Liver Transplantation: Can It Be Improved? A Retrospective Multicenter European Study.

OBJECTIVE: To evaluate the European experience after Adult-to-adult living donor liver transplantation using the left liver (LL-aLDLT). SUMMARY BACKGROUND DATA: LL-aLDLT decreases donor risk but provides a smaller graft that increases recipient risk as compared with right liver (RL-aLDLT). However, there is little knowledge of results obtained after LL-aLDLT in Europe. METHODS: This is a European multicenter retrospective study which aims to analyze donor and recipient outcomes after 46 LL-aLDLT. RESULTS: Seventy-six percent of the grafts were harvested by minimally invasive approach. Mean donor hospital stay was 7.5 ±â€Š3.5 days. Donor liver function was minimally impaired, with 36 donors (78.3%) without any 90-day complication, and 4 (8.7%) presenting major complications. One, 3, and 5-year recipient survival was 90.9%, 82.7%, and 82.7%, respectively. However, graft survival was of 59.4%, 56.9%, and 56.9% at 1, 3, and 5 years respectively, due to a 26.1% urgent liver retransplantation (ReLT) rate, mainly due to SFSS (n = 5) and hepatic artery thrombosis (HAT, n = 5). Risk factor analysis for ReLT and HAT showed an association with a graft to body weight ratio (GBWR) <0.6% (P = 0.01 and P = 0.024, respectively) while SFSS was associated with a recipient MELD ≥14 (P = 0.019). A combination of donor age <45 years, MELD <14 and actual GBWR >0.6% was associated with a lower ReLT rate (0% vs. 33%, P = 0.044). CONCLUSIONS: Our analysis showed low donor morbidity and preserved liver function. Recipient outcomes, however, were hampered by a high ReLT rate. A strict selection of both donor and recipients is the key to minimize graft loss.

Pilot study of living donor liver transplantation for patients with hepatocellular carcinoma exceeding Milan Criteria (Barcelona Clinic Liver Cancer extended criteria).

A subset of patients with hepatocellular carcinoma (HCC) beyond Milan criteria might obtain acceptable survival outcomes after liver transplantation. Living donor liver transplantation (LDLT) has emerged as a feasible alternative to overcome the paucity of donors. In 2001, we started a protocol for LDLT in Child A-B patients with HCC fulfilling a set of criteria-the Barcelona Clinic Liver Cancer (BCLC) expanded criteria-that expanded the conventional indications of transplantation: 1 tumor ≤ 7 cm, 5 tumors ≤ 3 cm, and 3 tumors ≤ 5 cm without macrovascular invasion or downstaging to Milan after locoregional therapies. We present a prospective cohort of 22 patients with BCLC extended indications based on size/number (n = 17) or downstaging (n = 5) treated with LDLT between 2001 and 2014. Characteristics of the patients were as follows: median age, 57 years old; males/female, n = 20/2; Child-Pugh A/B, n = 16/6; and alpha fetoprotein < 100 ng/mL, n = 21. Twelve patients received neoadjuvant locoregional therapies. At the time of transplantation, 12 patients had HCC staging beyond Milan criteria and 10 within. Pathological reports showed that 50% exceeded BCLC expanded criteria. Perioperative mortality was 0%. After a median follow-up of 81 months, the 1-, 3-, 5-, and 10-year survival was 95.5%, 86.4%, 80.2%, and 66.8%, respectively. Overall, 7 patients recurred (range, 9-108 months), and the 5-year and 10-year actuarial recurrence rates were 23.8% and 44.4%, respectively. In conclusion, a proper selection of candidates for extended indications of LDLT for HCC patients provide survival outcomes comparable to those obtained within the Milan criteria, but these results need confirmation. Liver Transplantation 24 369-379 2018 AASLD.

Heparin but not tissue plasminogen activator improves outcomes in donation after circulatory death liver transplantation in a porcine model.

Ischemic-type biliary lesions (ITBLs) arise most frequently after donation after circulatory death (DCD) liver transplantation and result in high morbidity and graft loss. Many DCD grafts are discarded out of fear for this complication. In theory, microvascular thrombi deposited during donor warm ischemia might be implicated in ITBL pathogenesis. Herein, we aim to evaluate the effects of the administration of either heparin or the fibrinolytic drug tissue plasminogen activator (TPA) as means to improve DCD liver graft quality and potentially avoid ITBL. Donor pigs were subjected to 1 hour of cardiac arrest (CA) and divided among 3 groups: no pre-arrest heparinization nor TPA during postmortem regional perfusion; no pre-arrest heparinization but TPA given during regional perfusion; and pre-arrest heparinization but no TPA during regional perfusion. In liver tissue sampled 1 hour after CA, fibrin deposition was not detected, even when heparin was not given prior to arrest. Although it was not useful to prevent microvascular clot formation, pre-arrest heparin did offer cytoprotective effects during CA and beyond, reflected in improved flows during regional perfusion and better biochemical, functional, and histological parameters during posttransplantation follow-up. In conclusion, this study demonstrates the lack of impact of TPA use in porcine DCD liver transplantation and adds to the controversy over whether the use of TPA in human DCD liver transplantation really offers any protective effect. On the other hand, when it is administered prior to CA, heparin does offer anti-inflammatory and other cytoprotective effects that help improve DCD liver graft quality. Liver Transplantation 24 665-676 2018 AASLD.