Incidence Of Primary Nonfunction Research Articles

Outcomes of lung and liver transplantation after simultaneous recovery using abdominal normothermic regional perfusion in donors after the circulatory determination of death versus donors after brain death

Normothermic regional perfusion (NRP) in controlled donation after the circulatory determination of death (cDCD) is a growing preservation technique for abdominal organs that coexists with the rapid recovery of lungs. We aimed to describe the outcomes of lung transplantation (LuTx) and liver transplantation (LiTx) when both grafts are simultaneously recovered from cDCD donors using NRP and compare them with grafts recovered from donation after brain death (DBD) donors. All LuTx and LiTx meeting these criteria during January 2015 to December 2020 in Spain were included in the study. Simultaneous recovery of lungs and livers was undertaken in 227 (17%) donors after cDCD with NRP and 1879 (21%) DBD donors (P < .001). Primary graft dysfunction grade-3 within the first 72 hours was similar in both LuTx groups (14.7% cDCD vs. 10.5% DBD; P = .139). LuTx survival at 1 and 3 years was 79.9% and 66.4% in cDCD vs. 81.9% and 69.7% in DBD (P = .403). The incidence of primary nonfunction and ischemic cholangiopathy was similar in both LiTx groups. Graft survival at 1 and 3 years was 89.7% and 80.8% in cDCD vs. 88.2% and 82.1% in DBD LiTx (P = .669). In conclusion, the simultaneous rapid recovery of lungs and preservation of abdominal organs with NRP in cDCD donors is feasible and offers similar outcomes in both LuTx and LiTx recipients to transplants using DBD grafts.

Kidney Transplantation After Rescue Allocation-the Eurotransplant Experience: A Retrospective Multicenter Outcome Analysis.

At Eurotransplant (ET), kidneys are transferred to "rescue allocation" (RA), whenever the standard allocation (SA) algorithms Eurotransplant Kidney Allocation System (ETKAS) and Eurotransplant Senior Program (ESP) fail. We analyzed the outcome of RA. Retrospective patient clinical and demographic characteristics association analyses were performed with graft outcomes for 2422 recipients of a deceased donor renal transplantation (DDRT) after RA versus 25 481 after SA from 71 centers across all ET countries from 2006 to 2018. Numbers of DDRTs after RA increased over the time, especially in Germany. RA played a minor role in ESP versus ETKAS (2.7% versus 10.4%). RA recipients and donors were older compared with SA recipients and donors, cold ischemia times were longer, waiting times were shorter, and the incidence of primary nonfunction was comparable. Among ETKAS recipients, HLA matching was more favorable in SA (mean 3.7 versus 2.5). In multivariate modeling, the incidence of graft loss in ETKAS recipients was reduced in RA compared with SA (subdistribution hazard ratio, 0.80; 95% confidence interval [0.70-0.91], P < 0.001), whereas other outcomes (mortality, death with functioning graft (DwFG)) were not significantly different. None of the 3 outcomes were significantly different when comparing RA with SA within the ESP program. Facing increased waiting times and mortality on dialysis due to donor shortage, this study reveals encouragingly positive DDRT outcomes following RA. This supports the extension of RA to more patients and as an alternative tool to enable transplantation in patients in countries with prohibitively long waiting times or at risk of deterioration.

Simultaneous nephrectomy during kidney transplantation for polycystic kidney disease does not detrimentally impact comorbidity and graft survival.

BACKGROUNDThe lack of space, as an indication for a native unilateral nephrectomy for positioning a future kidney graft in the absence of other autosomal dominant polycystic kidney disease-related symptoms, remains controversial.AIMTo evaluate the surgical comorbidity and the impact on graft survival of an associated ipsilateral native nephrectomy during isolated kidney transplantation in patients with autosomal dominant polycystic kidney disease. METHODSOne hundred and fifty-four kidney transplantations performed between January 2007 and January 2019 of which 77 without (kidney transplant alone (KTA) group) and 77 with associated ipsilateral nephrectomy (KTIN group), were retrospectively reviewed. Demographics and surgical variables were analyzed and their respective impact on surgical comorbidity and graft survival. RESULTSCreation of space for future graft positioning was the main reason (n = 74, 96.1%) for associated ipsilateral nephrectomy. No significant difference in surgical comorbidity (lymphocele, wound infection, incisional hernia, wound hematoma, urinary infection, need for blood transfusion, hospitalization stay, Dindo Clavien classification and readmission rate) was observed between the two study groups. The incidence of primary nonfunction and delayed graft function was comparable in both groups [0% and 2.6% (P = 0.497) and 9.1% and 16.9% (P = 0.230), respectively, in the KTA and KTIN group]. The 1- and 5-year graft survival were 94.8% and 90.3%, and 100% and 93.8%, respectively, in the KTA and KTIN group (P = 0.774). The 1- and 5-year patient survival were 96.1% and 92.9%, and 100% and 100%, respectively, in the KTA and KTIN group (P = 0.168). CONCLUSIONSimultaneous ipsilateral native nephrectomy to create space for graft positioning during kidney transplantation in patients with autosomal dominant polycystic kidney disease does not negatively impact surgical comorbidity and short- and long-term graft survival.

Risk factors of early liver dysfunction after liver transplantation using grafts from donation after citizen death donors

BackgroundAs an early complication after liver transplantation, early allograft dysfunction (EAD) indicates a poor prognosis. This study analyzes the risk factors related to early allograft dysfunction (EAD) after liver transplantation using grafts from donation after citizen death (DCD) to provide a reference for the prevention of EAD after DCD liver transplantation. MethodsA total of 32 patients who underwent DCD liver transplantation in the organ transplantation center of our hospital from September 2013 to January 2021 were enrolled in this study. The patients were divided into the EAD group and non-EAD group according to whether they developed EAD after transplantation. The general data of the donors and recipients before transplantation, intraoperative conditions, and clinical data within one week after transplantation were compared between the two groups, and related complications were statistically analyzed. The follow-up time was one week postoperatively or, if they died within the first week postoperatively, until the patient died. ResultsThe subjects included 10 females and 22 males, and the incidence of postoperative EAD was 25% (8/32). Four patients (12%) had primary malignant tumors (primary liver cancer and cholangiocarcinoma), and five donors (15%) had fatty liver. The univariate analysis revealed that the donor BMI (P = 0.005), degree of fatty liver (P = 0.025), aspartate aminotransferase (P = 0.001), alanine aminotransferase (P < 0.001), and total bilirubin (P = 0.009) were related to the occurrence of EAD after DCD liver transplantation. By analyzing the correlation between the incidence EAD and postoperative complications after liver transplantation using grafts from DCD donors, it was shown that the incidence of primary nonfunction (PNF) is related to EAD (P = 0.024). ConclusionDonor BMI, the degree of fatty liver, and preoperative liver function are risk factors for EAD after DCD liver transplantation, and the occurrence of EAD after DCD liver transplantation significantly increases the probability of PNF.

Primary graft nonfunction in liver transplantation: can we predict? A single-center experience

Background Primary nonfunction (PNF) after liver transplantation is a lethal condition, requiring immediate retransplantation. The precise cause is not well known yet. The aim of this study is to determine the incidence of PNF in our liver recipients, potential risk factors, and outcome. Patients and methods A total of 248 adult liver transplant recipients from 2014 till 2017 at our Transplant Unit were included after excluding nine patients for missing data. Of 248 patients, five (2%) had PNF; two of these patients have been excluded for the purpose of data analysis, as they had machine perfusion (One Liver Assist, and the other Organox). Of the non-PNF 243 recipients, 36 patients receiving livers from donors undergoing in-situ normothermic regional perfusion or ex-situ normothermic perfusion were not included, leaving 207 patients, so the total number was 210 patients. Donor and graft variables studied including age, BMI, serum sodium, cold ischemia time, warm ischemia time, operative time, graft type, and severity of steatosis. Recipient variables included primary liver disease; United Kingdom Model for End-Stage Liver Disease (UKELD) score; posttransplant biochemistry; potential risk factors, including dialysis, inotropes, mechanical ventilation, and pretransplant portal vein thrombosis; hospital and ICU stay; and patient survival. Results UKELD score was the only significant recipient variable (P=0.044). Among donor and graft variables, notably all PNF patients received donation after circulatory death grafts. Posttransplant laboratory values were strikingly worse, clearly indicating more pronounced hepatic and renal impairment in PNF group. Creatinine levels on days 1, 3, and 5 were significantly worse. Hospital and ICU stays were longer for PNF group, with ICU stay significantly longer [median of 7 vs. 2 days (P=0.014)], with no death in PNF group. Conclusion The main risk factors for PNF in our practice were donation after circulatory death grafts and more sick (higher UKELD) recipients.

The Impact of Hypothermic Pulsatile Machine Perfusion Versus Static Cold Storage: A Donor-Matched Paired Analysis in a Scenario of High Incidence of Delayed Kidney Graft Function.

BackgroundThe present study analyzed the impact of hypothermic pulsatile machine perfusion (MP) following a long period of static cold (SC) storage in the peculiar Brazilian scenario of high incidence of delayed graft function (DGF), despite good donor characteristics.Material/MethodsA retrospective analysis, with a 1-year follow-up, of 206 recipients of donor-matched paired kidneys was performed. Of the 206 donor kidneys, 103 were maintained exclusively in static cold storage (SC group) and 103 were kept on machine perfusion after a period of SC preservation (MP group). All donors were brain dead.ResultsOnly 4.9% of the kidneys were from expanded-criteria donors. Static cold ischemia time (CIT) in the SC group was 20.8±4.1 hours vs. 15.8±6.2 hours in the MP group (P<0.001). Dynamic CIT in the MP group was 12.3±5.7 hours. MP significantly reduced DGF incidence (29.1% vs. 55.3%, P<0.001), and this effect was confirmed in multivariable analysis (OR, 1.115; 95% CI, 1.033–1.204, P=0.001). No differences were observed between the groups with regard to DGF duration, length of hospital stay, incidence of primary nonfunction and acute rejection, graft loss, death, or renal function.ConclusionsIn this Brazilian setting, MP following a long period of SC preservation was associated with reduced DGF incidence in comparison with SC storage without MP.

Incidence and risk factors of primary non-function after liver transplantation using grafts from uncontrolled donors after circulatory death.

Graft primary non-function (PNF) is the most severe complication after orthotopic liver transplantation (OLT) and is frequently associated with livers from uncontrolled circulatory death (uDCD). We reviewed retrospectively the incidence, risk factors, and outcome of patients showing PNF after receiving uDCD liver grafts. The series comprises 75 OLT performed during 11years. The incidence of PNF using uDCD livers was 8%. We compared patients who developed PNF (n=6) vs. patients without PNF (n=69). Mean pump flow of donors during normothermic regional perfusion (NRP) was significantly lower in PNF (p=.032). Day 1 post-OLT levels of transaminases and the incidence of renal complications and postoperative mortality were also significantly higher in the PNF group, but 5-year patient survival was similar in both groups (66.7% in PNF and 68.5% in non-PNF). All PNF patients underwent re-OLT, and 2 died. PNF incidence has decreased in the last 5-years. Binary logistic regression analysis confirmed final ALT value >4 times the normal value as risk factor for PNF, and median donor pump flow >3700ml/min as protective effect. Adequate donor pump flow during NRP was a protective.

Indocyanine Green Fluorescence Imaging to Predict Graft Survival After Orthotopic Liver Transplantation: A Pilot Study

The incidence of primary nonfunction (PNF) after liver transplantation (LT) remains a major concern with the increasing use of marginal grafts. Indocyanine green (ICG) fluorescence is an imaging technique used in hepatobiliary surgery and LT. Because few early predictors are available, we aimed to quantify in real time the fluorescence of grafts during LT to predict 3-month survival. After graft revascularization, ICG was intravenously injected, and then the fluorescence of the graft was captured with a near infrared camera and postoperatively quantified. A multiparametric modeling of the parenchymal fluorescence intensity (FI) curve was proposed, and a predictive model of graft survival was tested. Between July 2017 and May 2019, 76 LTs were performed, among which 6 recipients underwent retransplantation. No adverse effects of ICG injection were observed. The parameter a150 (temporal course of FI) was significantly higher in the re-LT group (0.022seconds-1 (0.0011-0.059) versus 0.012seconds-1 (0.0001-0.054); P=0.01). This parameter was the only independent predictive factor of graft survival at 3 months (OR,2.4; 95% CI, 1.05-5.50; P=0.04). The best cutoff for the parameter a150 (0.0155seconds-1 ) predicted the graft survival at 3 months with a sensitivity (Se) of 83.3% and a specificity (Spe) of 78.6% (area under the curve,0.82; 95% CI, 0.67-0.98; P=0.01). Quantitative assessment of intraoperative ICG fluorescence on the graft was feasible to predict graft survival at 3months with a good Se and Spe. Further prospective studies should be undertaken to validate these results over larger cohorts and evaluate the clinical impact of this tool.

Repeated kidney re-transplantation-the Eurotransplant experience: a retrospective multicenter outcome analysis.

In Eurotransplant kidney allocation system (ETKAS), candidates can be considered unlimitedly for repeated re-transplantation. Data on outcome and benefit are indeterminate. We performed a retrospective15-year patient and graft outcome data analysis from 1464 recipients of a third or fourth or higher sequential deceased donor renal transplantation (DDRT) from 42 transplant centers. Repeated re-DDRT recipients were younger (mean 43.0 vs. 50.2years) compared to first DDRT recipients. They received grafts with more favorable HLA matches (89.0% vs. 84.5%) but thereby no statistically significant improvement of patient and graft outcome was found as comparatively demonstrated in 1st DDRT. In the multivariate modeling accounting for confounding factors, mortality and graft loss after 3rd and ≥4th DDRT (P<0.001 each) and death with functioning graft (DwFG) after 3rd DDRT (P=0.001) were higher as compared to 1st DDRT. The incidence of primary nonfunction (PNF) was also significantly higher in re-DDRT (12.7%) than in 1st DDRT (7.1%; P<0.001). Facing organ shortage, increasing waiting time, and considerable mortality on dialysis, we question the current policy of repeated re-DDRT. The data from this survey propose better HLA matching in first DDRT and second DDRT and careful selection of candidates, especially for ≥4th DDRT.

Uncontrolled Donation After Circulatory Death: A Unique Opportunity.

Uncontrolled donation after circulatory death (uDCD) refers to donation from persons who die following an unexpected and unsuccessfully resuscitated cardiac arrest. Despite the large potential for uDCD, programs of this kind only exist in a reduced number of countries with a limited activity. Barriers to uDCD are of a logistical and ethical-legal nature, as well as arising from the lack of confidence in the results of transplants from uDCD donors. The procedure needs to be designed to reduce and limit the impact of the prolonged warm ischemia inherent to the uDCD process, and to deal with the ethical issues that this practice poses: termination of advanced cardiopulmonary resuscitation, extension of advanced cardiopulmonary resuscitation beyond futility for organ preservation, moment to approach families to discuss donation opportunities, criteria for the determination of death, or the use of normothermic regional perfusion for the in situ preservation of organs. Although the incidence of primary nonfunction and delayed graft function is higher with organs obtained from uDCD donors, overall patient and graft survival is acceptable in kidney, liver, and lung transplantation, with a proper selection and management of both donors and recipients. Normothermic regional perfusion has shown to be critical to achieve optimal outcomes in uDCD kidney and liver transplantation. However, the role of ex situ preservation with machine perfusion is still to be elucidated. uDCD is a unique opportunity to improve patient access to transplantation therapies and to offer more patients the chance to donate organs after death, if this is consistent with their wishes and values.

Hypothermic machine perfusion reduces the incidences of early allograft dysfunction and biliary complications and improves 1-year graft survival after human liver transplantation: A meta-analysis.

Background:The worldwide organ shortage continues to be the main limitation of liver transplantation. To bridge the gap between the demand and supply of liver grafts, it becomes necessary to use extended criteria donor livers for transplantation. Hypothermic machine perfusion (HMP) is designed to improve the quality of preserved organs before implantation. In clinical liver transplantation, HMP is still in its infancy.Methods:A systematic search of the PubMed, EMBASE, Springer, and Cochrane Library databases was performed to identify studies comparing the outcomes in patients with HMP versus static cold storage (SCS) of liver grafts. The parameters analyzed included the incidences of primary nonfunction (PNF), early allograft dysfunction (EAD), vascular complications, biliary complications, length of hospital stay, and 1-year graft survival.Results:A total of 6 studies qualified for the review, involving 144 and 178 liver grafts with HMP or SCS preservation, respectively. The incidences of EAD and biliary complications were significantly reduced with an odds ratio (OR) of 0.36 (95% confidence interval [CI] 0.17–0.77, P = .008) and 0.47 (95% CI 0.28–0.76, P = .003), respectively, and 1-year graft survival was significantly increased with an OR of 2.19 (95% CI 1.14–4.20, P = .02) in HMP preservation compared to SCS. However, there was no difference in the incidence of PNF (OR 0.30, 95% CI 0.06–1.47, P = .14), vascular complications (OR 0.69, 95% CI 0.29–1.66, P = .41), and the length of hospital stay (mean difference −0.30, 95% CI −4.10 to 3.50, P = .88) between HMP and SCS preservation.Conclusions:HMP was associated with a reduced incidence of EAD and biliary complications, as well as an increased 1-year graft survival, but it was not associated with the incidence of PNF, vascular complications, and the length of hospital stay.

Order of liver graft revascularization in deceased liver transplantation: A systematic review and meta-analysis

BackgroundThe ideal order for liver graft revascularization during liver transplantation remains unknown. The majority of liver transplant centers prefer portal venous reperfusion followed by arterial reperfusion to shorten the warm ischemia time. The aim of this study was to review the different revascularization techniques used in clinical liver transplantation to identify any potential clinical benefits. MethodsA systematic search of 5 databases was performed to identify all available original articles that reported liver transplantation and compared different techniques of reperfusion. The primary outcomes were patient and graft survival. Secondary outcomes were defined by postreperfusion syndrome, primary nonfunction, vascular complications, biliary complications, and retransplantation. ResultsA total of 1,160 patients undergoing liver transplantation from 15 studies were included in this review and meta-analysis. There were no differences regarding the 1-year patient and graft survival for the revascularization techniques. The incidence of primary nonfunction, vascular complications, and retransplantation did not differ between the groups. Although there were no differences regarding biliary complications between the different groups, there were more nonanastomotic strictures in patients with initial portal revascularization (9%) compared with those with simultaneous revascularization (2%; risk ratio 1.07; 95% confidence interval, 1.00−1.14; P = .05; I2 = 51%). ConclusionThe order of liver graft revascularization does not influence patient and graft survival. Each revascularization technique offers potential benefits that can be used under specific clinical situations.

Machine perfusion preservation versus static cold storage for deceased donor kidney transplantation.

Kidney transplantation is the optimal treatment for end-stage kidney disease. Retrieval, transport and transplant of kidney grafts causes ischaemia reperfusion injury. The current accepted standard is static cold storage (SCS) whereby the kidney is stored on ice after removal from the donor and then removed from the ice box at the time of implantation. However, technology is now available to perfuse or "pump" the kidney during the transport phase or at the recipient centre. This can be done at a variety of temperatures and using different perfusates. The effectiveness of treatment is manifest clinically as delayed graft function (DGF), whereby the kidney fails to produce urine immediately after transplant. To compare hypothermic machine perfusion (HMP) and (sub)normothermic machine perfusion (NMP) with standard SCS. We searched the Cochrane Kidney and Transplant Register of Studies to 18 October 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. All randomised controlled trials (RCTs) and quasi-RCTs comparing HMP/NMP versus SCS for deceased donor kidney transplantation were eligible for inclusion. All donor types were included (donor after circulatory (DCD) and brainstem death (DBD), standard and extended/expanded criteria donors). Both paired and unpaired studies were eligible for inclusion. The results of the literature search were screened and a standard data extraction form was used to collect data. Both of these steps were performed by two independent authors. Dichotomous outcome results were expressed as risk ratio (RR) with 95% confidence intervals (CI). Continuous scales of measurement were expressed as a mean difference (MD). Random effects models were used for data analysis. The primary outcome was incidence of DGF. Secondary outcomes included: one-year graft survival, incidence of primary non-function (PNF), DGF duration, long term graft survival, economic implications, graft function, patient survival and incidence of acute rejection. No studies reported on NMP, however one ongoing study was identified.Sixteen studies (2266 participants) comparing HMP with SCS were included; 15 studies could be meta-analysed. Fourteen studies reported on requirement for dialysis in the first week post-transplant (DGF incidence); there is high-certainty evidence that HMP reduces the risk of DGF when compared to SCS (RR 0.77; 95% CI 0.67 to 0.90; P = 0.0006). HMP reduces the risk of DGF in kidneys from DCD donors (7 studies, 772 participants: RR 0.75; 95% CI 0.64 to 0.87; P = 0.0002; high certainty evidence), as well as kidneys from DBD donors (4 studies, 971 participants: RR 0.78, 95% CI 0.65 to 0.93; P = 0.006; high certainty evidence). The number of perfusions required to prevent one episode of DGF (number needed to treat, NNT) was 7.26 and 13.60 in DCD and DBD kidneys respectively. Studies performed in the last decade all used the LifePort machine and confirmed that HMP reduces the incidence of DGF in the modern era (5 studies, 1355 participants: RR 0.77, 95% CI 0.66 to 0.91; P = 0.002; high certainty evidence). Reports of economic analysis suggest that HMP can lead to cost savings in both the North American and European settings.Two studies reported HMP also improves graft survival however we were not able to meta-analyse these results. A reduction in incidence of PNF could not be demonstrated. The effect of HMP on our other outcomes (incidence of acute rejection, patient survival, hospital stay, long-term graft function, duration of DGF) remains uncertain. HMP is superior to SCS in deceased donor kidney transplantation. This is true for both DBD and DCD kidneys, and remains true in the modern era (studies performed in the last decade). As kidneys from DCD donors have a higher overall DGF rate, fewer perfusions are needed to prevent one episode of DGF (7.26 versus 13.60 in DBD kidneys).Further studies looking solely at the impact of HMP on DGF incidence are not required. Follow-up reports detailing long-term graft survival from participants of the studies already included in this review would be an efficient way to generate further long-term graft survival data.Economic analysis, based on the results of this review, would help cement HMP as the standard preservation method in deceased donor kidney transplantation.RCTs investigating (sub)NMP are required.

Kidney transplantation from donors after uncontrolled circulatory death: the Spanish experience

Donation after uncontrolled circulatory death (uDCD) refers to donation from persons who have died following cardiac arrest and unsuccessful attempt at resuscitation. We report the Spanish experience of uDCD kidney transplantation, and identify factors related to short-term post-transplant outcomes. The Spanish CORE system compiles data on all donation and transplant procedures in the country. Between 2012-2015, 517 kidney transplants from 288 uDCD donors were performed. The incidence of primary non-function was 10%, and the incidence of delayed graft function was 76%. One-year death-censored graft survival was 87%. In a Cox-Model, donor age≥ 60 years (odds ratio [OR] 2.7; 95% confidence interval [CI] 1.2-6.1), in situ cooling of kidneys versus normothermic regional perfusion (OR 5.6; 95% CI 2.7-11.5) or hypothermic regional perfusion based on the use of extracorporeal membrane oxygenation devices (OR 4.3; 95% CI 2.1-8.6), and a recipient history of prior kidney transplant (OR 3.5; 95% CI 1.5-8.3) all significantly increased the risk of graft loss during the first year after transplantation. Kidney transplantation from uDCD donors provides acceptable1-year outcomes, although there is room for improvement. Hypothermic and normothermic regional perfusion strategies are preferable to in situ cooling of kidneys from uDCD donors.

Donor Dopamine Does Not Affect Liver Graft Survival: Evidence of Safety From a Randomized Controlled Trial.

Treatment of donation after brain death (DBD) donors with low-dose dopamine improves the outcomes after kidney and heart transplantation. This study investigates the course of liver allografts from multiorgan donors enrolled in the randomized dopamine trial between 2004 and 2007 (clinicaltrials.gov identifier: NCT00115115). There were 264 hemodynamically stable DBDs who were randomly assigned to receive low-dose dopamine. Dopamine was infused at 4 μg/kg/minute for a median duration of 6.0 hours (interquartile range, 4.4-7.5 hours). We assessed the outcomes of 212 liver transplantations (LTs) performed at 32 European centers. Donors and recipients of both groups were very similar in baseline characteristics. Pretransplant laboratory Model for End-Stage Liver Disease score was not different in recipients of a dopamine-treated versus untreated graft (18 ± 8 versus 20 ± 8; P = 0.12). Mean cold ischemia time was 10.6 ± 2.9 versus 10.1 ± 2.8 hours (P = 0.24). No differences occurred in biopsy-proven rejection episodes (14.4% versus 15.7%; P = 0.85), requirement of hemofiltration (27.9% versus 31.5%; P = 0.65), the need for early retransplantation (5.8% versus 6.5%; P > 0.99), the incidence of primary nonfunction (7.7% versus 8.3%; P > 0.99), and in-hospital mortality (15.4% versus 14.8%; P > 0.99). Graft survival was 71.2% versus 73.2% and 59.6% versus 62.0% at 2 and 3 years (log-rank P = 0.71). Patient survival was 76.0% versus 78.7% and 65.4% versus 69.4% at 1 and 3 years (log-rank P = 0.50). In conclusion, donor pretreatment with dopamine has no short-term or longterm effects on outcome after LT. Therefore, low-dose dopamine pretreatment can safely be implemented as the standard of care in hemodynamically stable DBDs.

Better Graft Survival with no Ischemic Cholangiopathy in DCD Liver Transplantation in the UK using Normothermic Regional Perfusion (NRP)

Background Normothermic regional perfusion, whereby the donor is placed on an extracorporeal circuit to circulate oxygenated blood to the abdominal viscera after death, is increasingly being used in controlled donation after circulatory death (DCD) donation. We evaluated the joint experience of the two centres pioneering this technique in the UK and compared NRP DCD liver transplants to non-NRP DCD livers transplanted at each centre in the same period. Methods Between 1/1/2011 and 31/5/17, 44 patients underwent liver transplantation following NRP; these were compared to 185 DCD liver transplants without NRP performed in the same period. NRP was performed for a median 123 (IQR 101-130) minutes before in-situ cold perfusion. Results Table 1 summarises the results. There was no significant difference in the recipient age (58 vs 61) or UK End Stage Liver disease (UKELD) score (55.7 NRP vs 54.3 non-NRP) between groups. 90 day patient survival was similar (100% NRP vs 96.7% non-NRP). There was a significant reduction in ischemic cholangiopathy and early allograft dysfunction with a better graft survival at 90 days. Conclusion Livers from DCD donors undergoing NRP have a lower incidence of primary non function and early allograft dysfunction, fewer biliary complications, and significantly better early graft survival.

Compared efficacy of preservation solutions on the outcome of liver transplantation: Meta-analysis.

AIMTo compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations.METHODSA systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31st, 2017. The inclusion criteria were comparative, randomized controlled trials (RCTs) for deceased donor liver (DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin (UW) solution or histidine-tryptophan-ketoglutarate (HTK), Celsior (CS) and Institut Georges Lopez (IGL-1) solutions. Fifteen RCTs (1830 livers) were included; the primary outcomes were primary non-function (PNF) and one-year post-transplant graft survival (OGS-1).RESULTSAll trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, CS and IGL-1 (RR = 0.02, 95%CI: 0.01-0.03, P = 0.356). Comparing OGS-1 also failed to reveal any difference between UW, HTK, CS and IGL-1 (RR = 0.80, 95%CI: 0.80-0.80, P = 0.369). Two trials demonstrated higher PNF levels for UW in comparison with the HTK group, and individual studies described higher rates of biliary complications where HTK and CS were used compared to the UW and IGL-1 solutions. However, the meta-analysis of the data did not prove a statistically significant difference: the UW, CS, HTK and IGL-1 solutions were associated with nearly equivalent outcomes.CONCLUSIONAlternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted.

Emerging Innovations in Liver Preservation and Resuscitation

The availability of marginal liver grafts represents a potential resource of orthotopic liver transplantation (OLT) in the era of organ shortage. However, an increased susceptibility to ischemia-reperfusion injury results in the increased risk for primary nonfunction and biliary complications. Novel methods of organ preservation and resuscitation are under investigation to improve outcomes of OLT with the use of marginal grafts. Machine perfusion (MP) in OLT is categorized based on the temperature setting. Hypothermic MP minimizes oxygen demand and uses single- or dual-vessel infusion with or without oxygenation. Normothermic MP increases the metabolic rate to the physiologic level, and requires dual-vessel infusion with a higher blood flow rate with oxygenation typically by blood as an oxygen carrier. Midthermic or subnormothermic MP uses medium temperature settings to allow metabolic activity to maintain cellular integrity as well as decrease oxygen demand. Since 2010, a total of 9 clinical trials have investigated the safety and feasibility of hypothermic and normothermic MP. The results suggest that the incidence of primary nonfunction was minimal even when marginal grafts were used. Organ preservation time could be reasonably increased. MP offers an opportunity to assess the viability and time to apply therapeutic interventions. This review highlights the history of MP, mechanisms of different temperature settings in MP, and recent large animal studies and clinical trials in OLT.

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.

Effect of donor-specific antibodies and panel reactive antibodies in living donor liver transplant recipients.

PurposePreformed circulating donor-specific antibodies (DSAs) immunologically challenge vascular endothelium and the bile duct. However, the liver is an immune-tolerant organ and can avoid immunological challenges. This study was undertaken to analyze the effects of DSAs after adult living donor liver transplantation (LDLT).MethodsWe retrospectively reviewed 219 LDLT patients' records treated at our center.ResultsOf the 219 patients, 32 (14.6%) were DSA (+) and 187 (85.4%) were DSA (-). Class I DSAs were present in 18 patients, class II in seven patients, and both in seven patients. Seven patients (3.2%) showed DSA to HLA-A, four (1.8%) to HLA-B, seven (3.2%) to HLA-DR, and 14 (6.4%) to two or more HLAs. More DSAs were observed in female recipients than male recipients in the DSA (+) group. The DSA (+) group showed significantly higher levels of class I and II panel reactive antibody (PRA) than did the DSA (-) group. No significant intergroup differences were found between incidences of primary nonfunction, acute rejection, vascular complication, or biliary complication. There were no significant differences in graft survival rates between the two groups. However, the recipients with multiple DSAs tended to have more acute rejection episodes and events of biliary stricture and lower graft survival rates than did patients in the DSA (-) group.ConclusionIn LDLT, the presence of multiple DSAs and high PRA seemed to be associated with poor graft outcomes, although our results did not reach statistical significance. Large cohort studies are necessary to clarify the impact of DSA and PRA in LDLT.