Cardiac Death Liver Transplantation Research Articles

THU-497 - Long-term outcomes following donation after cardiac death (DCD) liver transplantation in primary sclerosing cholangitis (PSC)

THU-497 - Long-term outcomes following donation after cardiac death (DCD) liver transplantation in primary sclerosing cholangitis (PSC)

O120 A functional assessment of hepatic ischaemic injury on hepatocellular carcinoma behaviour

Abstract Introduction Hypothermic oxygenated perfusion (HOPE) preservation improves outcomes after donation after cardiac death (DCD) liver transplantation. Database analysis has also suggested significantly lower hepatocellular carcinoma (HCC) recurrence rates in recipients with HOPE-DCD livers compared to non-perfused livers. Whilst HOPE may protect against severe hepatic ischaemia-reperfusion injury, the exact mechanisms for lower recurrence rates are not fully understood. As HOPE preservation fluid, or perfusate, dynamically flushes out many inflammatory and ischaemic markers from the donor liver, the effect of these contents on in-vitro HCC cell behaviour was investigated. Methods An HCC cell line, HepG2, was functionally assessed following treatment with HOPE perfusate samples from 3 human livers declined for transplant. In-vitro HepG2 proliferation, stemness and initiation were assessed by an MTS assay, cytokeratin-19 (K-19) immunocytochemistry, and a colony-forming assay respectively. All experiments were conducted with approval by an ethical committee. Results All 3 HOPE perfusate samples resulted in significant HepG2 proliferation and increased aggressive behaviour potential. At 24 hours, HepG2 proliferation was significantly greater after treatment with 1:2 perfusate dilution compared to blank perfusate (p<0.05). Membrane invadopodia development, signifying an increased invasive potential, was also noted at 24 hours with treatments of 1:2 and 1:20, without observed differences in K-19 expression compared to untreated controls. Conclusion End-timepoint HOPE perfusate from declined livers facilitate increased HepG2 proliferation and aggression. HOPE may reduce early tumour recurrence in HCC patients by dynamically flushing out these liver-secreted trophic factors.

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.

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.

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.

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.

Can we reduce ischemic cholangiopathy rates in donation after cardiac death liver transplantation after 10 years of practice? Canadian single-centre experience

Can we reduce ischemic cholangiopathy rates in donation after cardiac death liver transplantation after 10 years of practice? Canadian single-centre experience

Can we reduce ischemic cholangiopathy rates in donation after cardiac death liver transplantation after 10 years of practice? Canadian single-centre experience

Outcomes in liver transplantation with organs obtained via donation after cardiocirculatory death (DCD) have been suboptimal compared to donation after brain death, attributed mainly to the high incidence of ischemic cholangiopathy (IC). We evaluated the effect of a 10-year learning curve on IC rates among DCD liver graft recipients at a single centre. We analyzed all DCD liver transplantation procedures from July 2006 to July 2016. Patients were grouped into early (July 2006 to June 2011) and late (July 2011 to July 2016) eras. Those with less than 6months of follow-up were excluded. Primary outcomes were IC incidence and IC-free survival rate. Among the 73DCD liver transplantation procedures performed, 70recipients fulfilled the selection criteria, 32 in the early era and 38 in the late era. Biliary complications were diagnosed in 19 recipients (27%). Ischemic cholangiopathy was observed in 8patients (25%) in the early era and 1patient (3%) in the late era (p= 0.005). The IC-free survival rate was higher in the late era than the early era (98% v. 79%, p= 0.01). The warm ischemia time (27 v. 24min, p= 0.049) and functional warm ischemia time (21 v. 17min, p= 0.002) were significantly lower in the late era than the early era. We found a significant reduction in IC rates and improvement in ICfree survival among DCD liver transplantation recipients after a learning curve period that was marked by more judicious donor selection with shorter procurement times.

Effect of the Selective NLRP3 Inflammasome Inhibitor mcc950 on Transplantation Outcome in a Pig Liver Transplantation Model With Organs From Donors After Circulatory Death Preserved by Hypothermic Machine Perfusion.

We investigated whether the outcome of organs from donors after circulatory death (DCD) can be improved by the addition of mcc950 to the perfusate of the hypothermic machine perfusion (HMP) system and intravenous mcc950 injection after transplantation in a pig liver transplantation model. Thirty-six healthy Bama mini pigs randomized into 3 groups. All the DCD livers were preserved in an HMP system after 2 hours of simple cold storage. In HMP-Postop group, mcc950 was added to the perfusate; in the control group and Postop group, the perfusate was normal LPS. After transplantation, the pigs in the Postop group and HMP-Postop group were intravenously administered 3 mg/kg mcc950, at the time of reperfusion and on day 2 and day 3 after transplantation. During the 3-day follow-up period, general operative characteristics, and serological markers and histological features related to ischemia reperfusion injury were examined. The HMP-Postop group suffer the lightest ischemia reperfusion injury (IRI), and functioned best after transplantation. Model for the Early Allograft Function Score (predictor of long-term survival), degree of injury in the hepatocytes and rate of apoptosis was lowest in the HMP-Postop group. Further, in the HMP-Postop group, the nucleotide-binding domain leucine-rich repeat containing family pyrin domain containing 3 inflammasome pathway activation was lowest, and the level of IL-1β was lowest. Postop group functioned better than control group, but not comparable with HMP-Postop group. The outcome of DCD organs can be improved by the addition of mcc950 to the perfusate of the HMP system and intravenous injection of mcc950 after transplantation.

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.

Research Highlights

Improving the Supply and Quality of Deceased-Donor Organs for Transplantation Tullius SG, Rabb H. N Engl J Med. 2018;378:1920-1929. A timely review article, summarizing the potential improvements that can be made to decrease the discard rate of deceased-donor organs. Deceased-donor organs are generally discarded if considered suboptimal. The Kidney Donor Risk Profile Index is widely used to predict outcome, and a score of 85% or more are discarded frequently. Using these organs will particularly impact on the highly sensitized patients, as well as patients who are on the waiting list for more than 10 years. A variety of reasons can deem the organ unsuitable, from older-age donors to infectious risk or increased warm ischemic time. The authors point out that with death rates between 20% and 40% on the waiting list, it is time for clinicians to think of innovative ways to deal with these suboptimal organs and to reduce the discard rate. Although age is not limiting donor utilization in countries like Spain, there are several places elsewhere in the world where donors older than 65 or 70 years might not be used. Spanish results with older donors are not yet well reported, although we know, in general, that using these kidneys for older recipients result in better outcomes.1 Eliminating harmful senescent cells, which are more prevalent in older organs, might improve organ function. This is a potential research area that needs to be developed in more detail. Similarly, new preservation methods have the option to improve organs retrieved from donors after circulatory death and normothermic perfusion will hopefully impact positively to reduce discard rates from donors after circulatory death organs. Lastly, the authors point out that donors with high infectious risk can successfully be used, including hepatitis C virus– and human immunodeficiency virus–positive organs. The key is probably to select the best recipient for all these organs and to adjust regulatory frameworks to allow for a wider use of discarded organs. A huge potential exists to improve organ quality in the brain-dead donor, including improved hemodynamic stabilization, hormonal factors, and metabolic factors. REFERENCE Tullius SG, Milford E. Kidney allocation and the aging immune response. N Engl J Med. 2011;364:1369–1370. A Randomized Trial of Normothermic Preservation in Liver Transplantation Nasralla D, Coussio CC, Mergental H, et al. Nature. 2018;557:50-56. Suboptimal livers do not tolerate conventional cold storage very well and organ viability is difficult to assess. In this study, 334 livers were randomized to 2 groups. In the first group, 170 livers were perfused with oxygenated blood, medications, and nutrients at normal body temperature (normothermic machine perfusion [NMP]). In the second group, 164 livers were allocated to static cold storage (SCS). Livers donated after circulatory death (DCD), as well as livers from brain-dead donors (DBD), were allowed into the study. The discard rate in the SCS group was 24.1% compared with the 11.7% in the NMP arm. Peak aspartate aminotransferase AST was reduced by 49.4% in the NMP arm at day 7 compared with the SCS arm. There was no significant difference in the rate of nonanastomotic bile duct strictures for DBD livers (NMP, 7.4% vs SCS, 5.4%). The DCD liver donors represent a large untapped source of organ donors worldwide and had been used less often because of increased risk of ischemic cholangiopathy compared with DBD livers.1 The effects of NMP demonstrated in this study are unequivocal with respect to the primary endpoint, implying a benefit in livers currently used for transplantation. However, the greatest benefit may be realized by applying this technology to livers outside current acceptance criteria, to transplant organs currently deemed untransplantable. REFERENCE Jay CL, Lyuksemburg V, Ladner DP, et al. Ischemic cholangiopathy after controlled donation after cardiac death liver transplantation: a meta-analysis. Ann Surg. 2011;253:259–264.

Hypothermic oxygenated perfusion (HOPE) attenuates ischemia/reperfusion injury in the liver through inhibition of the TXNIP/NLRP3 inflammasome pathway in a rat model of donation after cardiac death.

Hypothermic oxygenated perfusion (HOPE) is a relatively new dynamic preservation procedure that has not been widely implemented in liver transplantation despite its advantages. Improved graft protection is one such advantage offered by HOPE and has been attributed to multiple mechanisms, one of which may be the modulation of the thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) inflammasome pathway. The TXNIP/NLRP3 inflammasome pathway plays a critical role in sterile inflammation under oxidative stress as a result of ischemia/reperfusion injury (IRI). In the current study, we aimed to investigate the graft protection offered by HOPE and its impact on the TXNIP/NLRP3 inflammasome pathway. To simulate conditions of donation after cardiac death (DCD) liver transplantation, rat livers were exposed to 30 min of warm ischemia after cardiac arrest. Livers were then preserved under cold storage (CS) or with HOPE for 3 h. Livers were then subjected to 1 h of isolated reperfusion. Liver injuries were assessed on the isolated perfusion rat liver model system before and after reperfusion. Compared with the CS group, the HOPE group had a significant reduction in liver injury and improvement in liver function. Our findings also revealed that reperfusion injury induced liver damage and activated the TXNIP/NLRP3 inflammasome pathway in DCD rat livers. Pretreatment of DCD rat livers with HOPE inhibited the TXNIP/NLRP3 inflammasome pathway and attenuated liver IRI. Attenuation of oxidative stress as a result of HOPE led to the down-regulation of the TXNIP/NLRP3 inflammasome pathway and thus offered superior protection compared with the traditional CS method of organ preservation.-He, W., Ye, S., Zeng, C., Xue, S., Hu, X., Zhang, X., Gao, S., Xiong, Y., He, X., Vivalda, S., Li, L., Wang, Y., Ye, Q. Hypothermic oxygenated perfusion (HOPE) attenuates ischemia/reperfusion injury in the liver through inhibition of the TXNIP/NLRP3 inflammasome pathway in a rat model of donation after cardiac death.

Description of organ-specific phenotype, and functional characteristics of tissue resident lymphocytes from liver transplantation donor and research on immune tolerance mechanism of liver.

AimPrior to transplantation, Donation after Cardiac Death (DCD) liver transplantation livers are perfused with preservation solution. Therefore, this provides an abundant source of human liver lymphocytes, as well as mesenteric lymph node and spleen for the study of lymphocyte subset diversity in the peripheral blood, lymph node, spleen and liver.MethodsLymphocyte subsets were isolated and purified from peripheral blood, lymph node, spleen and liver perfusion, the phenotypic and functional analysis of the tissue resident lymphocyte were performed by flow cytometry.ResultsIn a direct comparison between blood, liver, lymph node and spleen cells from liver transplantation donors, the abundance of natural killer (NK) cells, CD3+CD56+NKT (NT) cells and CD8+ T cells in intrahapatic lymphocytes (IHL) did not match what was present in peripheral blood and other peripheral lymphoid organs. The activation state of peripheral blood-derived lymphocytes was significantly different from lymph node-, spleen- and liver-derived cells. Intriguingly, NK cells, CD4+ T cells, and CD8+ T cells from liver perfusion display more suppressive characteristics, that is, express and produce more anti-inflammatory cytokine interleukin (IL)-10, less inflammatory cytokine interferon (INF)-γ.ConclusionOur findings imply that different tissues entail resident lymphocyte subsets with a distinct phenotype and function considering the organ is well vascularized, particularly in liver. It is better to understand the mechanism of liver immune tolerance.

Outcomes of Controlled Donation After Cardiac Death Compared With Donation After Brain Death in Liver Transplantation: A Systematic Review and Meta-analysis

BackgroundControlled donation after cardiac death (CDCD) is increasingly common for liver transplantation due to donor shortage. However, the outcomes, in terms of grafts and recipients, remain unclear. The current study is a systematic review and meta-analysis that compared CDCD with donation after brain death (DBD). MethodsWe conducted an electronic search of MEDLINE, EMBASE, and the Cochrane Database (from January 2007 to May 2017). Studies reporting Maastricht category III or IV CDCD liver transplantation were screened for inclusion. We appraised studies using the Newcastle-Ottawa scale and meta-analyzed using a fixed or random effects model. ResultsA total of 21 studies, with 12,035 patients, were included in data analysis. CDCD did not differ from DBD in patient survival (hazard ration: 1.20; 95% confidence interval [CI]: 0.98 to 1.47; P = .07), graft survival (hazard ratio: 1.24; 95% CI: 0.99 to 1.56; P = .06), primary nonfunction (odds ratio [OR]: 1.74; 95% CI: 1.00 to 3.03; P = .05), hepatic artery thrombosis (OR: 1.17; 95% CI: 0.78 to 1.74; P = .45). However, CDCD was associated with biliary complications (OR: 2.48; 95% CI: 2.05 to 3.00), retransplantation (OR: 2.54; 95% CI: 1.99 to 3.26), and peak alanine aminotransferase (weighted mean difference: 330.88; 95% CI: 259.88 to 401.87). A subgroup analysis that included only hepatitis C virus (HCV)–positive recipients showed no significant difference between CDCD and DBD in biliary complications (P = .16), retransplantion (P = .15), HCV recurrence (P = .20), and peak alanine aminotransferase (P = .06). ConclusionsCDCD transplantation is the most viable alternative to DBD transplantation in the current critical shortage of liver organs. HCV infection may not be the inferior factor of postoperative outcomes and survival.

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.

Safety and Outcomes in 100 Consecutive Donation After Circulatory Death Liver Transplants Using a Protocol That Includes Thrombolytic Therapy.

Donation after circulatory death (DCD) liver transplantation (LT) reportedly yields inferior survival and increased complication rates compared with donation after brain death (DBD). We compare 100 consecutive DCD LT using a protocol that includes thrombolytic therapy (late DCD group) to an historical DCD group (early DCD group n = 38) and a cohort of DBD LT recipients (DBD group n = 435). Late DCD LT recipients had better 1- and 3-year graft survival rates than early DCD LT recipients (92% vs. 76.3%, p = 0.03 and 91.4% vs. 73.7%, p = 0.01). Late DCD graft survival rates were comparable to those of the DBD group (92% vs. 93.3%, p = 0.24 and 91.4% vs. 88.2%, p = 0.62). Re-transplantation occurred in 18.4% versus 1% for the early and late DCD groups, respectively (p = 0.001). Patient survival was similar in all three groups. Ischemic-type biliary lesions (ITBL) occurred in 5%, 3%, and 0.2% for early DCD, late DCD, and DBD groups, respectively, but unlike in the early DCD group, in the late DCD group ITBL was endoscopically managed and resolved in each case. Using a protocol that includes a thrombolytic therapy, DCD LT yielded patient and graft survival rates comparable to DBD LT.