Donation After Cardiac Death Liver Transplantation Research Articles

Dynamic changes of hepatic microenvironment related to graft function in donation after cardiac death liver transplantation

PurposeThe study aimed to evaluate dynamic changes in the liver microenvironment at 3 weeks, 3 months, and 6 months following donation after cardiac death liver transplantation (DCDLT) using multiparametric MRI, and further explore the correlation between the hepatic microenvironment and liver function after DCDLT. MethodsTwenty-seven patients after DCDLT (the LT group) at times of 3 weeks (LT-3W), 3 months (LT-3M), and 6 months (LT-6M) and 20 normal volunteers (the N group) underwent intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), and blood oxygen level-dependent (BOLD) MR scanning. One-way repeated-measures ANOVA was used to compare MR parameters and liver volume (LV)/estimated standard liver volume (ESLV) at three follow-up times in the LT group. An independent sample t-test was used to compare MR parameters and LV/ESLV between each time of the LT group and the N group. Pearson and Spearman correlation analyses were employed to assess the correlation between MR parameters and liver blood indicators, LV/ESLV after DCDLT. ResultsAfter DCDLT, true diffusion coefficient (Dslow), pseudo diffusion coefficient (Dfast), perfusion fraction (PF), and apparent diffusion coefficient (ADC) values were increased, and fractional anisotropy (FA) and R2* values were decreased. Dfast values in the LT-3M and LT-6M were significantly higher than in the LT-3W. Compared to the LT-3W, PF and ADC values were significantly increased and R2* values were significantly decreased in the LT-6M (all P < 0.05). All MR parameters in the LT-3W were significantly different from the N group, and Dfast and ADC values in the LT-6M remained significantly higher than in the N group (all P < 0.05). In the LT group, Dslow, Dfast, PF, and ADC values were correlated with liver blood indicators and LV/ESLV (|r| = 0.364–0.561, all P < 0.05). ConclusionAfter DCDLT, the hepatic microenvironment showed an improving trend, which was correlated to the liver function. Except for the microcirculatory perfusion, the hepatic microenvironment was close to normality at six months.

Applicability of the UK DCD risk score in the modern era of liver transplantation: A U.S. update.

Careful graft and recipient selection have resulted in improved outcomes in liver transplantation (LT) using donation after cardiac death (DCD) organs. The UK DCD Risk Score was established as a risk stratification tool to guide selection. We evaluated the applicability of the UK DCD Risk Score in a contemporary US cohort of adult DCD LT recipients using the United Network for Organ Sharing registry (2011-2020). A total of 3,899 DCD LTs were included in our study (UK DCD Risk Score 0-5 points: 1,438 [36.9%], 6-10 points: 2,034 [52.2%]; 11-20 points: 427 [11.0%]). Compared to a score of 6-10 points, a score of 0-5 points was associated with decreased risk of graft loss (HR=.79, 95%CI: .68-.93, p=.004), while a score of 11-20 points was associated with increased risk of graft loss (HR=1.26, 95%CI: 1.01-1.56, p=.04). The 5-year graft survival for patients with risk scores of 0-5, 6-10, and 11-20 were 75.9%, 71.8%, and 66.5%, respectively. The C-statistic for the UK DCD Risk Score in our contemporary cohort was .611. The UK DCD Risk Score demonstrates a more limited ability to differentiate recipient outcomes in the modern era of DCD LT in the US. Acceptable long-term outcomes are achievable for patients stratified to the highest-risk group.

HO-1/BMMSC perfusion using a normothermic machine perfusion system reduces the acute rejection of DCD liver transplantation by regulating NKT cell co-inhibitory receptors in rats

BackgroundLiver transplantation (LT) is required in many end-stage liver diseases. Donation after cardiac death (DCD) livers are often used, and treatment of acute rejection (ACR) requires the use of immunosuppressive drugs that are associated with complications. Bone marrow mesenchymal stem cells (BMMSCs) are used in treatment following LT; however, they have limitations, including low colonization in the liver. An optimized BMMSC application method is required to suppress ACR.MethodsBMMSCs were isolated and modified with the heme oxygenase 1 (HO-1) gene. HO-1/BMMSCs were perfused into donor liver in vitro using a normothermic machine perfusion (NMP) system, followed by LT into rats. The severity of ACR was evaluated based on liver histopathology. Gene chip technology was used to detect differential gene expression, and flow cytometry to analyze changes in natural killer (NK) T cells.ResultsNMP induced BMMSCs to colonize the donor liver during in vitro preservation. The survival of HO-1/BMMSCs in liver grafts was significantly longer than that of unmodified BMMSCs. When the donor liver contained HO-1/BMMSCs, the local immunosuppressive effect was improved and prolonged, ACR was controlled, and survival time was significantly prolonged. The application of HO-1/BMMSCs reduced the number of NKT cells in liver grafts, increased the expression of NKT cell co-inhibitory receptors, and reduced NKT cell expression of interferon-γ.ConclusionsNK cell and CD8+ T cell activation was inhibited by application of HO-1/BMMSCs, which reduced ACR of transplanted liver. This approach could be developed to enhance the success rate of LT.

Application of machine learning models for predicting acute kidney injury following donation after cardiac death liver transplantation

BackgroundAcute kidney injury (AKI) is a common complication after liver transplantation (LT) and is an indicator of poor prognosis. The establishment of a more accurate preoperative prediction model of AKI could help to improve the prognosis of LT. Machine learning algorithms provide a potentially effective approach. MethodsA total of 493 patients with donation after cardiac death LT (DCDLT) were enrolled. AKI was defined according to the clinical practice guidelines of kidney disease: improving global outcomes (KDIGO). The clinical data of patients with AKI (AKI group) and without AKI (non-AKI group) were compared. With logistic regression analysis as a conventional model, four predictive machine learning models were developed using the following algorithms: random forest, support vector machine, classical decision tree, and conditional inference tree. The predictive power of these models was then evaluated using the area under the receiver operating characteristic curve (AUC). ResultsThe incidence of AKI was 35.7% (176/493) during the follow-up period. Compared with the non-AKI group, the AKI group showed a remarkably lower survival rate (P < 0.001). The random forest model demonstrated the highest prediction accuracy of 0.79 with AUC of 0.850 [95% confidence interval (CI): 0.794–0.905], which was significantly higher than the AUCs of the other machine learning algorithms and logistic regression models (P < 0.001). ConclusionsThe random forest model based on machine learning algorithms for predicting AKI occurring after DCDLT demonstrated stronger predictive power than other models in our study. This suggests that machine learning methods may provide feasible tools for forecasting AKI after DCDLT.

Liver transplantation using grafts from donors after circulatory death - the first Czech Republic experience.

Liver transplantation is established as alifesaving procedure for patients with acute and chronic liver failure, as well as certain selected malignancies. Due to acontinuing organ shortage and ever-growing patient waiting lists, donation after cardiac death (DCD) is becoming more frequently utilized in order to close the gap between &#8220;supply and demand&#8221;. Aretrospective analysis of DCD and subsequent liver transplantations was performed. From May 2016 to September 2019, atotal of 9 DCD liver transplantations were performed in our institution. All cases except one were primary liver transplantations. The recipients comprised 5 (56%) males and 4 (44%) females. The mean DCD donor age was 41±12 (22-57) years, with ventilation duration of 7±1 days and warm ischemia time 19±3 minutes. The average recipient age was 51±22 (4-73) years, with an average cold ischemia 3h:59m±27m and manipulation time of 23±5 minutes. Periprocedural mortality was 1 (11%). Hepatitis C recurrence was documented in 1 (11%) patient. The mean follow-up time was 19±13 (7-37) months. Until now, we have not observed any signs of ischemic cholangiopathy. DCD liver transplantation allows us to enlarge the pool of potential liver grafts, thus decreasing the time spent on the liver recipient waiting list. This paper documents the first series of DCD liver transplantations in the Czech Republic.

Recipient gender and body mass index are associated with early acute rejection in donation after cardiac death liver transplantation

Early acute rejection (EAR) is a common complication after liver transplantation (LT). The aim of this study was to evaluate the incidence and risk factors of EAR in donation after cardiac death (DCD) liver transplantation recipients. We retrospectively analysed the data of 461 DCD liver transplants performed during the period from January 2010 to June 2016 to study the relationship between EAR and various clinical factors. EAR was defined as histologically proven acute cellular rejection occurring less than 90 days after transplantation. The median follow-up time for this study was 33.1 months (range: 0.03-92.8 months). Thirty-two (6.9%) patients developed EAR with a median period of 20.5 days (5-88 days) after transplantation. A multivariate analysis revealed that female recipient (hazard ratio: 2.801; P=0.024) and high recipient body mass index (BMI) (hazard ratio: 1.005; P=0.049) were two independent risk factors for early acute rejection. In DCD liver transplantation, recipient female gender and high BMI were associated with a higher incidence of EAR, while the use of CD25-Ab and/or MMF had a protective effect.

Results in liver transplantation using grafts from donors after controlled circulatory death: A single-center experience comparing donor grafts harvested after controlled circulatory death to those harvested after brain death.

In recent years, interest in donation after cardiac death (DCD) has increased. Although DCD liver transplantation (LT) has demonstrated satisfactory long-term outcomes, different studies have shown poorer patient and graft survival after DCD than after donation after brain death (DBD). This study aimed to evaluate the results of LT using controlled DCD (cDCD) donors, specifically the incidence of primary non-function and ischemic cholangiopathy (IC), and to compare these results with those of LT using DBD in the same time period. Between June 2012 and July 2018, we performed 66 transplants using cDCD and 258 with DBD grafts. The incidence of IC was similar in both groups (2% in DBD, 1.5% in DCD; P=.999). No significant differences were found for overall graft and patient survival rates between the groups at 1 and 2years post-transplantation. This study provided evidence that cDCD donors exhibit excellent graft and patient survival outcomes. When the warm ischemia time is <30minutes and cold ischemia time is <6hours, the graft and patient survival rates and the incidence of IC in DCD are similar to those in DBD, even when using donors without age restrictions.

Outcomes of endoscopic therapy in donation after cardiac death liver transplant biliary strictures

BackgroundBiliary strictures after donation-after-cardiac-death (DCD) liver transplantation (LT) require multiple endoscopic retrograde cholangiopancreatographies (ERCP). The outcomes of endoscopic dilation and maximal stenting are not well-characterized in this high-risk population. MethodsDCD LT recipients who underwent LT and ERCP from 2012–2018 were selected. Anastomotic and non-anastomotic strictures were treated with balloon dilation and maximal stenting. A successful stent-free trial was defined as absence of biochemical, clinical or imaging evidence of strictures on follow-up exceeding 6 months. Adverse events were defined as unplanned admission or inpatient evaluation within 7 days of ERCP. ResultsForty-nine DCD LT recipients underwent ERCP and 34 patients were diagnosed with strictures (20 anastomotic). Stent-free trial was successful in 27 patients. Adverse events occurred after 20 ERCPs. Patients with anastomotic strictures required fewer stents (1.43 ± 1.37 vs 2.63 ± 1.66; P < 0.001), shorter procedure and fluoroscopy times (34.15 ± 20.9 vs 59.6 ± 30.7 minutes, P < 0.001; 5.99 ± 7.4 vs 14.73 ± 10.74 minutes, P < 0.001), fewer relapses (10% vs 57%, P = 0.003), shorter intervals between initial ERCP and stent-free success (136.9 ± 118.3 vs 399.56 ± 234.7; P = 0.003), and between LT and stent-free success (227.8 ± 171.9 vs 464.1 ± 224.6 days; P = 0.005) compared to non-anastomotic strictures. ConclusionEndoscopic dilation and maximal stenting resolves biliary strictures in DCD LT recipients with sustained success and relatively few adverse events.

Impact of Donor Hepatectomy Time During Organ Procurement in Donation After Circulatory Death Liver Transplantation: The United Kingdom Experience

No data exist to evaluate how hepatectomy time (HT), in the context of donation after cardiac death (DCD) procurement, impacts short- and long-term outcomes after liver transplantation (LT). In this study, we analyze the impact of the time from aortic perfusion to end of hepatectomy on outcomes after DCD LT in the United Kingdom. An analysis of 1112 DCD donor LT across all UK transplant centers between 2001 and 2015 was performed, using data from the UK Transplant Registry. Donors were all Maastricht Category III. Graft survival after transplantation was estimated using Kaplan-Meier method and logistic regression to identify risk factors for primary nonfunction (PNF) and short- and long-term graft survivals after LT. Incidence of PNF was 4% (40) and in multivariate analysis only cold ischemia time (CIT) longer than 8 hours (hazard ratio [HR], 2.186; 95% confidence interval [CI], 1.113-4.294; P = 0.023) and HT > 60 minutes (HR, 3.669; 95% CI, 1.363-9.873; P = 0.01) were correlated with PNF. Overall 90-day, 1-, 3-, and 5-year graft survivals in DCD LT were 91.2%, 86.5%, 80.9%, and 77.7% (compared with a donation after brain death cohort in the same period [n = 7221] 94%, 91%, 86.6%, and 82.6%, respectively [P < 0.001]). In multivariate analysis, the factors associated with graft survival were HT longer than 60 minutes, donor older than 45 years, CIT longer than 8 hours, and recipient previous abdominal surgery. There is a negative impact of prolonged HT on outcomes on DCD LT and although HT is 60 minutes or longer is not a contraindication for utilization, it should be part of a multifactorial assessment with established prognostic donor factors, such as age (>45 y) and CIT (>8 h) for an appropriately selected recipient.

Predictors of Biliary Strictures After Liver Transplantation Among Recipients of DCD (Donation After Cardiac Death) Grafts

Biliary strictures are a common complication among donation after cardiac death (DCD) liver transplantation (LT) recipients and may require multiple endoscopic retrograde cholangiopancreatography (ERCP) procedures. We evaluated the risk factors associated with development of biliary strictures in DCD LT recipients. DCD LT recipients who underwent transplantation from 2012 to 2017 were divided into 2 groups: (a) those with anastomotic or non-anastomotic biliary strictures who required ERCP ("stricture group") and (b) those who did not require ERCP or had cholangiograms without evidence of biliary strictures ("non-stricture group"). Clinical data, cholangiograms and laboratory values at day 0 and day 7 after LT were compared between the two groups. Forty-nine of the 100 DCD LT recipients underwent ERCP. Thirty-four of these 49 LT recipients had evidence of anastomotic or non-anastomotic biliary strictures (stricture group), while the remaining 66 LT recipients comprised the non-stricture group. Donor age was significantly higher in stricture group compared to non-stricture group (49.2 ± 1.8 vs 42.8 ± 1.57years, respectively; p = 0.01). The stricture group had a significantly higher total bilirubin at day 0 (3.5 ± 0.37 vs 2.6 ± 0.21mg/dL; p = 0.02) and INR at day 7 (1.24 ± 0.06 vs 1.13 ± 0.01; p = 0.048) compared to the non-stricture group. Multi-variate analysis demonstrated significant association between biliary strictures and total bilirubin at day 0 of LT and age of donor. Biliary strictures occur frequently in DCD LT recipients and may be associated with older age of donor. Hyperbilirubinemia immediately after transplant and higher INR in the first 7days after transplant may predict subsequent development of biliary strictures.

Recipient Gender and Body Mass Index are Associated with Early Acute Rejection in Donation after Cardiac Death Liver Transplantation

Background: Early acute rejection (EAR) is a common complication after liver transplantation (LT). The purpose of this study was to evaluate the incidence and risk factors of EAR in donation after cardiac death (DCD) liver transplantation recipients. Methods: We retrospectively analyzed the data of 461 DCD liver transplants performed during the period from January 2010 to June 2016 to study the relationship between EAR and various clinical factors. EAR was defined as histologically proven acute cellular rejection occurring less than 90 days after transplantation. Findings: The median follow-up time for this study was 33.1 months (range, 0.03-92.8months). Thirty-two (6.9%) patients developed EAR with a median period of 20.5 days (5-88 days) after transplantation. A multivariate analysis revealed that female recipient (hazard ratio, 2.801; P = 0.024) and high recipient body mass index (BMI) (hazard ratio, 1.005; P = 0.049) were two independent risk factors for early acute rejection. A multivariate analysis was performed in order to evaluate the factors that influenced the overall survival, the result revealed that HCC (hazard ratio, 2.308；P <0.001), ABO-incompatibility (hazard ratio, 1.793；P =0.001) and operation time≥360 minutes (hazard ratio, 1.627; P = 0.012) were the independent prognostic factors for overall survival after liver transplantation. Interpretation: Recipients' gender and BMI are related to early acute rejection in DCD liver transplant. HCC, ABO-incompatibility and OT ≥360 minutes are the independent prognostic factors for overall survival. Funding Statement: This work was supported by grants from National Natural Science Foundation of China (Grant No. 81800578), the Changjiang Scholar Program of Chinese Ministry of Education (No. T2014146) and National S&T Major Project (No. 2017ZX10203205). Declaration of Interests: The authors who have taken part in this study declare that they do not have any potential conflicts (financial, professional, or personal) that are relevant to the manuscript. Ethics Approval Statement: Each organ donation and transplantation strictly followed the guidelines of the Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine, the current regulation of the Chinese Government and the Declaration of Helsinki.

Warm ischemia time and elevated serum uric acid are associated with metabolic syndrome after liver transplantation with donation after cardiac death.

AIMTo describe the prevalence of posttransplant metabolic syndrome (PTMS) after donation after cardiac death (DCD) liver transplantation (LT) and the pre- and postoperative risk factors.METHODSOne hundred and forty-seven subjects who underwent DCD LT from January 2012 to February 2016 were enrolled in this study. The demographics and the clinical characteristics of pre- and post-transplantation were collected for both recipients and donors. PTMS was defined according to the 2004 Adult Treatment Panel-III criteria. All subjects were followed monthly for the initial 6 mo after discharge, and then, every 3 mo for 2 years. The subjects were followed every 6 mo or as required after 2 years post-LT.RESULTSThe prevalence of PTMS after DCD donor orthotopic LT was 20/147 (13.6%). Recipient’s body mass index (P = 0.024), warm ischemia time (WIT) (P = 0.045), and posttransplant hyperuricemia (P = 0.001) were significantly associated with PTMS. The change in serum uric acid levels in PTMS patients was significantly higher than that in non-PTMS patients (P < 0.001). After the 1st mo, the level of serum uric acid of PTMS patients rose continually over a period, while it was unaltered in non-PTMS patients. After transplantation, the level of serum uric acid in PTMS patients was not associated with renal function.CONCLUSIONPTMS could occur at early stage after DCD LT with growing morbidity with the passage of time. WIT and post-LT hyperuricemia are associated with the prevalence of PTMS. An increased serum uric acid level is highly associated with PTMS and could act as a serum marker in this disease.

Systematic Review and Meta-Analysis on the Impact of Thrombolytic Therapy in Liver Transplantation Following Donation after Circulatory Death.

Aim: The livers from DCD (donation after cardiac death) donations are often envisaged as a possible option to bridge the gap between the availability and increasing demand of organs for liver transplantation. However, DCD livers possess a heightened risk for complications and represent a formidable management challenge. The aim of this study was to evaluate the effects of thrombolytic flush in DCD liver transplantation. Methods: An extensive search of the literature database was made on MEDLINE, EMBASE, Cochrane, Crossref, Scopus databases, and clinical trial registry on 20 September 2018 to assess the role of thrombolytic tissue plasminogen activator (tPA) flush in DCD liver transplantation. Results: A total of four studies with 249 patients in the tPA group and 178 patients in the non-tPA group were included. The pooled data revealed a significant decrease in ischemic-type biliary lesions (ITBLs) (P = 0.04), re-transplantation rate (P = 0.0001), and no increased requirement of blood transfusion (P = 0.16) with a better one year graft survival (P = 0.02). Conclusions: To recapitulate, tPA in DCD liver transplantation decreased the incidence of ITBLs, re-transplantation and markedly improved 1-year graft survival, without any increased risk for blood transfusion, hence it has potential to expand the boundaries of DCD liver transplantation.

RNA Sequencing Reveals the Suitability of Cardiac Death Livers for Transplantation.

Background Organ transplantation is considered the best treatment for end-stage organ failure. However, the lack of available organs for transplantation and the increasing number of patients waiting for transplants are primary issues facing the transplant community. Thus, developing strategies to increase the number of donors, especially for liver transplantation, has become a priority. The use of organs acquired from donors who suffered cardiac related deaths has increased the pool of potential liver donors. However, donation after cardiac death (DCD) livers increases the risk of primary graft dysfunction. Methods In the current study, we conducted transcriptome sequencing using livers from a DCD rat to assess the short-term feasibility and functional efficacy of DCD livers. RNA sequencing (RNAseq) data showed that the liver transcriptome varied greatly in rat livers subjected to 15 minutes of cardiac arrest. Results The livers used in the current study had a significant loss of normal function before transplantation. Functional and network analyses consistently indicated that transcription and translation processes were inhibited after approximately 15 minutes of cardiac arrest. Moreover, the transcriptomic sequencing data provides significant insight for identifying functional genes and testing additional biological questions in DCD liver transplantation in future studies.

Peri-operative management of swine orthotopic liver transplantation

Objective To summarize the peri-operative management experience of swine orthotopic liver transplantation. Methods From September 2013 to August 2016, 62 liver transplantations (LT) were performed with 124 Bama mini-pigs, including 30 cases of standard LT, 10 cases of split LT, 11 cases of donation after cardiac death (DCD) LT, 5 cases of extracorporeal membrane oxygenation (ECMO) repaired DCD LT and 6 cases of normothermic machine perfusion (NMP) repaired DCD LT. Results For all of the 124 pigs, 3 underwent tracheotomy after failed tracheal intubation. Anhepatic time was (22.3±2.6) min (range 18-26 min), similar among the 62 different type LTs. Mean arterial pressure could be mainted ≥ 50 mmHg (1 mmHg=0.133 kPa) through rapid colloid solution infusion without administration of any vasoactive substances.5 receipts of split LTs died during the operation because of bleeding. 14 cases died after operation. 3 were of standard LT, all in the very beginning period when we first build this animal model, 1 died of abdominal bleeding, the other 2 died of bile leak induced severe infection.11 cases from the DCD LT died of model related hepatic failure. Post-operative 5-day survival rates of standard, split, DCD, ECMO-repaired DCD, NMP-repaired DCD were 90%, 50%, 0%, 100%, 100%, respectively. Conclusion Precise peri-operative management is essential for successful swine orthotopic liver transplantation. Skilled trachea intubation and tracheotomy procedure, accurate liquid management, well-practiced animal model are the key points, and anhepatic period should be shortened as much as possible. Key words: Pig; Liver transplantation; Peri-operative management

Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats.

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD.

Waitlist Outcomes for Patients Relisted Following Failed Donation After Cardiac Death Liver Transplant: Implications for Awarding Model for End-Stage Liver Disease Exception Scores.

Understanding of outcomes for patients relisted for ischemic cholangiopathy following a donation after cardiac death (DCD) liver transplant (LT) will help standardization of a Model for End-Stage Liver Disease exception scheme for retransplantation. Early relisting (E-RL) for DCD graft failure caused by primary nonfunction (PNF) or hepatic artery thrombosis (HAT) was defined as relisting ≤14 days after DCD LT, and late relisting (L-RL) due to biliary complications was defined as relisting 14 days to 3 years after DCD LT. Of 3908 DCD LTs performed nationally between 2002 and 2016, 540 (13.8%) patients were relisted within 3 years of transplant (168 [4.3%] in the E-RL group, 372 [9.5%] in the L-RL group). The E-RL and L-RL groups had waitlist mortality rates of 15.4% and 10.5%, respectively, at 3 mo and 16.1% and 14.3%, respectively, at 1 year. Waitlist mortality in the L-RL group was higher than mortality and delisted rates for patients with exception points for both hepatocellular carcinoma (HCC) and hepatopulmonary syndrome (HPS) at 3- to 12-mo time points (p < 0.001). Waitlist outcomes differed in patients with early DCD graft failure caused by PNF or HAT compared with those with late DCD graft failure attributed to biliary complications. In L-RL, higher rates of waitlist mortality were noted compared with patients listed with exception points for HCC or HPS.

Pediatric Donor to Adult Recipients in Donation After Cardiac Death Liver Transplantation: A Single-Center Experience

BackgroundThe impact of using liver allografts from donors who are younger than 14 years at the time of donation after cardiac death (DCD) liver transplantation in terms of early allograft dysfunction (EAD) and graft survival is undefined. To determine if adults undergoing DCD liver transplantation who receive a graft from a donor age younger than or equal to 13 years have similar outcomes to recipients of organs from older than 18-year-old donors. MethodsRecords from adult patients undergoing DCD liver transplantation between March 2012 and December 2015 who received whole grafts from donors after cardiac death were reviewed. Patients with donors younger than or equal to 13 years (group 1) and older than 18 years (group 2) were compared for EAD rates, hepatic artery thrombosis (HAT), and graft survival. ResultsRecords of 60 DCD liver transplantation patients were analyzed. The 90-day and 1-year graft survival rate of both groups was 90% versus 96% (P = .427) and 80% versus 84% (P = .668), respectively. The EAD rates of groups 1 and 2 were 30% versus 34% (P = .806). The incidence of HAT was 20% in group 1 compared with 12% in group 2 (P = .610). Also, 0.7% < graft to recipient weight ratio (GRWR) <0.8% was also usable for pediatric donor to adult recipients. ConclusionsWhole liver grafts from donors younger than or equal to 13 years can potentially be used in selected size-matched (GRWR >0.7%) DCD adult recipients.

Ursolic Acid Improves Liver Transplantation and Inhibits Apoptosis in Miniature Pigs Using Donation After Cardiac Death

Background: Ursolic acid (UA) possesses extensive pharmacological activities, including anti-oxidation, anti-infection, anti-inflammation, anti-tumor, liver protection. This study was designed to investigate the effect of UA on liver transplantation after liver transplantation using donation after cardiac death (DCD), and to assess the mechanisms. Methods: 24 healthy experimental pigs were randomly divided into control and experimental groups. Each group received six DCD liver transplantations. In the experimental group, the recipient pigs received 120 mg/kg UA 4 h before surgery by intraperitoneal injection. The liver tissues and vein blood were collected 0 h, 1 h, 3 h, 6 h, 12 h and 24 h after transplantation. Morphological change, malondialdehyde (MDA) level, protein kinase-like ER kinase (PERK)-CHOP signaling pathway and apoptosis in liver tissue and serum aminotransferase (ALT) level were assessed. Results: Compared with control group, ALT level was significantly decreased (P<0.05) and pathological changes in liver were ameliorated in experimental group. UA treatment also decreased MDA level in liver tissue and attenuated the apoptosis. Compared with control group, Bax decreased and Bcl-2 increased in UA-treated group. Importantly, UA decreased p-PERK, PERK, p-eIF2α, eIF2α, ATF4 and CHOP levels compared with control group. Conclusion: Our results showed that UA treatment could improve the DCD liver transplantation likely through inhibiting apoptosis and PERK-CHOP pathway.

Successful donation after cardiac death liver transplants with prolonged warm ischemia time using normothermic regional perfusion.

The role of donation after cardiac death (DCD) in expanding the donor pool is mainly limited by the incidence of primary nonfunction (PNF) and ischemia-related complications. Even greater concern exists toward uncontrolled DCD, which represents the largest potential pool of DCD donors. We recently started the first Italian series of DCD liver transplantation, using normothermic regional perfusion (NRP) in 6 uncontrolled donors and in 1 controlled case to deal with the legally required no-touch period of 20 minutes. We examined our first 7 cases for the incidence of PNF, early graft dysfunction, and biliary complications. Acceptance of the graft was based on the trend of serum transaminase and lactate during NRP, the macroscopic appearance, and the liver biopsy. Hypothermic machine perfusion (HMP) was associated in selected cases to improve cold storage. Most notably, no cases of PNF were observed. Median posttransplant transaminase peak was 1014 IU/L (range, 393-3268 IU/L). Patient and graft survival were both 100% after a mean follow-up of 6.1 months (range, 3-9 months). No cases of ischemic cholangiopathy occurred during the follow-up. Only 1 anastomotic stricture completely resolved with endoscopic stenting. In conclusion, DCD liver transplantation is feasible in Italy despite the protracted no-touch period. The use of NRP and HMP seems to earn good graft function and proves safe in these organs. Liver Transplantation 23 166-173 2017 AASLD.