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Similar liver transplantation survival with selected cardiac death donors and brain death donors
Abstract
The outcome of orthotopic liver transplantation (OLT) with controlled graft donation after cardiac death (DCD) is usually inferior to that with graft donation after brain death (DBD). This study compared outcomes from OLT with DBD versus controlled DCD donors with predefined restrictive acceptance criteria.
All adult recipients in the Netherlands in 2001-2006 with full-size OLT from DCD (n = 55) and DBD (n = 471) donors were included. Kaplan-Meier, log rank and Cox regression analyses were used.
One- and 3-year patient survival rates were similar for DCD (85 and 80 per cent) and DBD (86.3 and 80.8 per cent) transplants (P = 0.763), as were graft survival rates (74 and 68 per cent versus 80.4 and 74.5 per cent; P = 0.212). The 3-year cumulative percentage of surviving grafts developing non-anastomotic biliary strictures was 31 per cent after DCD and 9.7 per cent after DBD transplantation (P < 0.001). The retransplantation rate was similar overall (P = 0.081), but that for biliary stricture was higher in the DCD group (P < 0.001). Risk factors for 1-year graft loss after DBD OLT were transplant centre, recipient warm ischaemia time and donor with severe head trauma. After DCD OLT they were transplant centre, donor warm ischaemia time and cold ischaemia time. DCD graft was a risk factor for non-anastomotic biliary stricture.
OLT using controlled DCD grafts and restrictive criteria can result in patient and graft survival rates similar to those of DBD OLT, despite a higher risk of biliary stricture.
... Data on NAS and its therapy are still scant in the literature, even though NAS occurs in up to 30% of patients following orthotropic liver transplantation [1,10,[18][19][20][21][22][23][24]. The present study is, to the best of our knowledge, one of the largest trials with a focus on the treatment of NAS, and it is the first to evaluate NAS in both its subtypes (ITBL and IBL) for all three different types of strictures in the bile system. ...
... Limitations of this study were due to its retrospective character. Nonetheless, compared to previous studies, patients' characteristics and incidence of NAS appear representative [1,10,[18][19][20][21][22][23][24]31]. Further limitations were the single-center design and the limited number of patients, especially in the subgroup analysis. ...
Background:
Non-anastomotic biliary strictures (NAS) are a common cause of morbidity and mortality after liver transplantation.
Methods:
All patients with NAS from 2008 to 2016 were retrospectively analyzed. The success rate and overall mortality of an ERCP-based stent program (EBSP) were the primary outcomes.
Results:
A total of 40 (13.9%) patients with NAS were identified, of which 35 patients were further treated in an EBSP. Furthermore, 16 (46%) patients terminated EBSP successfully, and nine (26%) patients died during the program. All deaths were caused by cholangitis. Of those, one (11%) patient had an extrahepatic stricture, while the other eight patients had either intrahepatic (3, 33%) or combined extra- and intrahepatic strictures (5, 56%). Risk factors of overall mortality were age (p = 0.03), bilirubin (p < 0.0001), alanine transaminase (p = 0.006), and aspartate transaminase (p = 0.0003). The median duration of the stent program was 34 months (ITBL: 36 months; IBL: 10 months), and procedural complications were rare.
Conclusions:
EBSP is safe, but lengthy and successful in only about half the patients. Intrahepatic strictures were associated with an increased risk of cholangitis.
... Based on this success story, there is an increasing imbalance between available liver grafts and candidates, which forces transplant centres to increasingly utilize marginal grafts, including livers from donation after circulatory death (DCD) donors [2,3]. In context of different donor risk profiles in various countries and centres, outcomes were inconsistently reported, and results after LT from DCD donors were found equally good or inferior, compared to organs from donation after brain death (DBD) donors [4][5][6][7]. National and centre-specific guidelines, and surgeons experience with DCD grafts contributed significantly to the selection of DCD donors and related outcomes [8]. A recent systematic review and meta-analysis demonstrated with 3-39% a highly variable incidence of ischemic cholangiopathy (IC) after DCD liver transplantation [9]. ...
... In context of todays optimized liver transport and modern communication, CIT is generally shorter and more accurately estimated. The majority of analyses interpret CIT therefore in combination with the cumulative donor and recipient risk aiming for liver implantation within ≤8 or ideally ≤6hrs [5,23,38,51]. The median CIT in our overall DCD cohort was 6.25hrs (IQR:5.2-7.47hrs). ...
Background
To identify the best possible outcomes in liver transplantation from donation after circulatory death donors (DCD) and to propose outcome values, which serve as reference for individual liver recipients or patient groups.
Methods
Based on 2219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1012 low-risk, primary, adult liver transplantations with a laboratory MELD of ≤20points, receiving a DCD liver with a total donor warm ischemia time of ≤30minutes and asystolic donor warm ischemia time of ≤15minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the Comprehensive Complication Index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75th-percentile was considered.
Results
Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centers. The one-year retransplant and mortality rate was 5.23% and 9.01%, respectively. Within the first year of follow-up, 51.1% of recipients developed at least one major complication (≥Clavien-Dindo-Grade-III). Benchmark cut-offs were ≤3days and ≤16days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade-III), ≤16.8% for ischemic cholangiopathy, and ≤38.9CCI points at one-year posttransplant. Comparisons with higher risk groups showed more complications and impaired graft survival, outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk.
Conclusions
Despite excellent 1-year survival, morbidity in benchmark cases remains high with more than half of recipients developing severe complications during 1-year follow-up. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups, and provide a valid comparator cohort for future clinical trials.
Lay summary
The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2219 liver transplantations following controlled DCD donation in 17 centres worldwide.
The following benchmark cut-offs for the most relevant outcome parameters were developed:
ICU and hospital stay: ≤3 and ≤16 days; primary non function: ≤2.5%; renal replacement therapy: ≤9.6%; ischemic cholangiopathy: ≤16.8% and anastomotic strictures ≤28.4%. One-year graft loss and mortality were defined as ≤14.4% and 9.6%, respectively.
Donor and recipient combinations with higher risk had significantly worse outcomes. The use of novel organ perfusion technology achieved similar, good results in this high-risk group with prolonged donor warm ischemia time, when compared to the benchmark cohort.
... [6][7][8] Recently, outcomes of DCD LT have been comparable to those of DBD LT as a result of robust donor and recipient selection and surgical technique optimization, especially during procurement, as well as insights into the effects of warm ischemia time (WIT) and cold ischemia time (CIT) and the use of machine perfusion. [9][10][11][12][13] Patients with HCC are considered ideal candidates for DCD allografts because they tend to have preserved liver function and to be in better physical condition when listed for LT, making them able to tolerate potential complications associated with the use of marginal livers. [14][15][16] Moreover, compared with DBD LT , DCD LT procedures have been associated with a lower dropout rate and shorter time on the waitlist. ...
Objectives:
Liver transplant for patients with hepatocellular carcinoma involves 3 main types of donor allografts: donation after brain death, donation after cardiac death, and donation after brain and cardiac death. Data on this topic are limited, and controversies exist regarding liver transplant outcomes in hepatocellular carcinoma patients who have received these allografts.
Materials and methods:
Data from 490 hepatocellular carcinoma patients who received liver transplant from 2015 to 2021 at the Shulan (Hangzhou) Hospital were retrospectively analyzed. Participants were divided into 3 cohorts according to allograft type: donation after brain death, donation after cardiac death, and donation after brain and cardiac death. Kaplan-Meier and Cox regression methods were used to evaluate patient survival, graft survival, and recurrence-free survival rates after liver transplant.
Results:
Kaplan-Meier analysis revealed that 3-year patient survival rates were 69.2% for donations after brain death, 69.2% for donations after cardiac death, and 46.6% for donations after brain and cardiac death (P = .42); the 3-year graft survival rates were 53.3% for donations after brain death, 56.4% for donations after cardiac death, and 46.6% for donations after brain and cardiac death (P = .44); and 3-year recurrence-free survival rates were 55% for donations after brain death, 56.6% for donations after cardiac death, and 39.5% for donations after brain and cardiac death (P = .46). Complications were also similar across the 3 cohorts (P = .36). Multivariable analysis showed that intraoperative red blood cell transfusion (hazard ratio: 1.820; P = .042) and early allograft dysfunction (hazard ratio: 3.240; P = .041) were independent risk factors for graft survival.
Conclusions:
Similar outcomes can be achieved for hepatocellular carcinoma patients who undergo liver transplant with donations after brain death, donations after cardiac death, or donations after brain and cardiac death allografts, especially when strict donor selection criteria are applied.
... As a solution to this donor shortage, liver transplantation using expanded criteria donor (ECD) grafts, such as donation after cardiac death (DCD) and donors with fatty liver disease, has been explored [2][3][4][5]. The frequency of complications, including delayed graft function, primary nonfunction, and bile duct complications, is high in liver transplantation using DCD liver grafts, and more than half of them cannot be used without modification [6]. The efficiency of ex vivo machine perfusion (MP) for DCD liver grafts has been studied using hypothermic machine perfusion (HMP) [7] and normothermic MP [8]. ...
Ex vivo hypothermic machine perfusion (HMP) is a strategy for controlling ischemia-reperfusion injury in donation after circulatory death (DCD) liver transplantation. The pH of blood increases with a decrease in temperature and water dissociation, leading to a decrease in [H+]. This study aimed to verify the optimal pH of HMP for DCD livers. Rat livers were retrieved 30 min post-cardiac arrest and subjected to 3-h cold storage (CS) in UW solution (CS group) or HMP with UW-gluconate solution (machine perfusion [MP] group) of pH 7.4 (original), 7.6, 7.8, and 8.0 (MP-pH 7.6, 7.8, 8.0 groups, respectively) at 7–10 °C. The livers were subjected to normothermic perfusion to simulate reperfusion after HMP. All HMP groups showed greater graft protection compared to the CS group due to the lower levels of liver enzymes in the former. The MP-pH 7.8 group showed significant protection, evidenced by bile production, diminished tissue injury, and reduced flavin mononucleotide leakage, and further analysis by scanning electron microscopy revealed a well-preserved structure of the mitochondrial cristae. Therefore, the optimum pH of 7.8 enhanced the protective effect of HMP by preserving the structure and function of the mitochondria, leading to reduced reperfusion injury in the DCD liver.
... 6,29,30 This complication is the leading cause of re-transplantation and occurs in 2-12% of recipients of livers procured from brain dead donors. [31][32][33][34] In the current study, the incidence of non-anastomotic strictures based on protocol MRCP was reduced in the IFLT arm. Data from our previous study have shown that the integrity of microvilli in the common bile duct was better preserved in the IFLT vs. CLT group. ...
Background & aims:
Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes.
Methods:
In this randomized, controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. Primary end point was the incidence of early allograft dysfunction. Secondary end points included complications related to graft IRI.
Results:
65 out of 68 randomized patients underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in 2 (6%) randomized to IFLT and in 8 (24%) randomized to CLT (difference, -18%; 95% CI, -35% to -1%; P=.044). Post-reperfusion syndrome occurred in 3 (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference, -54%; 95% CI, -74% to -35%; P < .001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in 2 recipients (8%) randomized to IFLT and in 9 recipients (36%) randomized to CLT (difference, -28%; 95% CI, -50% to -7%; P = .014). The comprehensive complication index at one year after transplantation was 30.48 (95% CI, 23.25-37.71) in the IFLT group vs 42.14 (95% CI, 35.01-49.26) in the CLT group (difference, -11.66; 95% CI, -21.81 to -1.51; P = .025).
Conclusions:
Among patients with end-stage liver disease, IFLT, compared with conventional approach, significantly reduced complications related to ischemia reperfusion injury.
Clinical trial registration:
Chictr.org. ChiCTR1900021158 IMPACT AND IMPLICATIONS: Ischemia reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with conventional approach led to reduced complications related to ischemia reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.
... 12 Many single-center reports have demonstrated that equivalent graft and patient survival rates can be achieved between DCD and DBD LT with careful donor and recipient selection. [13][14][15][16][17][18] One underlying principle with DCD recipient selection is to avoid cases where increased surgical complexity is anticipated. This has raised the question as to what impact a recipient with PVT may have on outcomes following DCD LT. 4 In the present analysis, we demonstrate equivalent graft and patient survival in patients with PVT compared with a propensity matched group of patients without PVT undergoing DCD LT. ...
With donation after circulatory death (DCD) liver transplantation (LT), the goal of the recipient implantation procedure is to minimize surgical complexity to avoid a tenuous environment for an already marginal graft. The presence of portal vein thrombosis (PVT) at the time of LT adds surgical complexity, yet' to date, no studies have investigated the utilization of DCD liver grafts for patients with PVT.
Methods:
All DCD LT performed at Mayo Clinic-Florida, Mayo Clinic-Arizona, and Mayo Clinic-Rochester from 2006 to 2020 were reviewed (N = 771). Patients with PVT at the time of transplant were graded using Yerdel classification. A 1:3 propensity match between patients with PVT and those without PVT was performed.
Results:
A total of 91 (11.8%) patients with PVT undergoing DCD LT were identified. Grade I PVT was present in 62.6% of patients, grade II PVT in 27.5%, grade III in 8.8%, and grade 4 in 1.1%. At the time of LT, thromboendovenectomy was performed in 89 cases (97.8%). There was no difference in the rates of early allograft dysfunction (43.2% versus 52.4%; P = 0.13) or primary nonfunction (1.1% versus 1.1%; P = 0.41) between the DCD PVT and DCD without PVT groups, respectively. The rate of ischemic cholangiopathy was not significantly different between the DCD PVT (11.0%) and DCD without PVT groups (10.6%; P = 0.92). Graft (P = 0.58) and patient survival (P = 0.08) were similar between the 2 groups. Graft survival at 1-, 3-, and 5-y was 89.9%, 84.5%, and 79.3% in the DCD PVT group.
Conclusions:
In appropriately selected recipients with grades I-II PVT, DCD liver grafts can be utilized safely with excellent outcomes.
... Unlike PNF, EAD represents marginal, usually reversible, graft function during the first postoperative week, and results in a higher morbidity and mortality. 4 Compared with 1-10% seen in donation after brain death (DBD) LT, the incidence of biliary complications after DCD LT is approximately 10-30%, [19][20][21][22] in which the time from asystole to cross-clamp is considered as a ma-jor risk factor. 23 Moreover, advanced donor age, prolonged ischemia time, microvascular thrombosis, bile salt toxicity and immune injury may be the underlying mechanisms of the development of biliary complications. ...
Liver transplantation (LT) is the final treatment option for patients with end-stage liver disease. The increasing donor shortage results in the wide usage of grafts from extended criteria donors across the world. Using such grafts is associated with the elevated incidences of post-transplant complications including initial nonfunction and ischemic biliary tract diseases, which significantly reduce recipient survival. Although several clinical factors have been demonstrated to impact donor liver quality, accurate, comprehensive, and effective assessment systems to guide decision-making for organ usage, restoration or discard are lacking. In addition, the development of biochemical technologies and bioinformatic analysis in recent years helps us better understand graft injury during the perioperative period and find potential ways to restore graft function. Moreover, such advances reveal the molecular profiles of grafts or perfusate that are susceptible to poor graft function and provide insight into finding novel biomarkers for graft quality assessment. Focusing on donors and grafts, we updated potential biomarkers in donor blood, liver tissue, or perfusates that predict graft quality following LT, and summarized strategies for restoring graft function in the era of extended criteria donors. In this review, we also discuss the advantages and drawbacks of these potential biomarkers and offer suggestions for future research.
... (R Foundation, Vienna, Austria). 28 Benchmark recipients consisted of predominantly male patients (222 of 373; 60%), displayed a median age of 50 years (IQR: 39-59), and a median labMELD score of 17 points (IQR: [11][12][13][14][15][16][17][18][19][20][21][22]. The median donor age in the benchmark cohort was 49 years (IQR: 37-61), the median cold ischemia time was 7.5 hours (IQR: 6.1-9.2 hours). ...
Objective:
To define benchmark cutoffs for redo liver transplantation (redo-LT).
Background:
In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT.
Methods:
We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with MELD score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary non-function (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers.
Results:
Out of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index (CCI®) at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks.
Conclusion:
This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This major analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.
... (R Foundation, Vienna, Austria). 28 Benchmark recipients consisted of predominantly male patients (222 of 373; 60%), displayed a median age of 50 years (IQR: 39-59), and a median labMELD score of 17 points (IQR: [11][12][13][14][15][16][17][18][19][20][21][22]. The median donor age in the benchmark cohort was 49 years (IQR: 37-61), the median cold ischemia time was 7.5 hours (IQR: 6.1-9.2 hours). ...
Objective
In the era of organ shortage, redo liver transplantation (reLT) is frequently discussed in terms of expected poor outcome, high cost and therefore wasteful resources. However, there is a lack of benchmark data to reliably assess outcomes after reLT. The aim of this study was to define the ideal reLT case, and to establish clinically relevant benchmark values for best achievable outcome in reLT.
Methods
We collected data on reLT between January 2010 and December 2018 from 22 high volume transplant centers on three continents. Benchmark cases were defined as recipients with model of end-stage liver disease score <=25, absence of portal vein thrombosis, no mechanical ventilation before surgery, receiving a graft from a donor after brain death. In addition, early reLT including those for primary non-function (PNF) were excluded. Clinically relevant endpoints covering intra- and postoperative course were selected and complications were graded by severity using the Clavien-Dindo classification and the comprehensive complication index (CCI). The benchmark cutoff for each outcome was derived from the 75th percentile of the median values of all benchmark centers, indicating the “best achievable” result. To assess the utility of the newly established benchmark values, we analyzed patients who received reLT for PNF (non-benchmark patients).
Results
Out of 1110 reLT 413 (37.2%) qualified as benchmark cases. Benchmark values included: Length of intensive care unit and hospital stay: <=6 and <=24 days, respectively; Clavien-Dindo grade >=3a complications and the CCI at 1 year: <=76% and <=72.2, respectively; in-hospital and 1-year mortality rates: <=14.0% and <=14.3%, respectively. The cutoffs for transplant-specific complications such as biliary complications at 1 year, outflow problems at 1 year and hepatic artery thrombosis at discharge were <=27.3%, <=2.5% and <=4.8%, respectively. Patients receiving a reLT for PNF showed mean outcome values all outside the reLT benchmark values. In-hospital mortality rate was 34.4% and the mean CCI at discharge 68.8.
Conclusion
ReLT remains associated with high morbidity and mortality. The availability of benchmark values for outcome parameters of reLT may serve for comparison in any future analyses of individuals, patient groups, or centers, but also in the evaluation of new therapeutic strategies and principles.
... Among these, primary non-function and post-transplant biliary complications, including non-anastomotic stricture (NAS) of the bile ducts, are a frequent cause of post-transplant morbidity, early graft loss and patient death. [2][3][4][5][6][7] To overcome the limitations of SCS, dynamic preservation of donor livers using ex situ machine perfusion has recently entered into clinical practice. Two different types of ex situ liver machine perfusion are currently applied clinically: (dual) hypothermic oxygenated machine perfusion ([D]HOPE) and normothermic machine perfusion (NMP). ...
Ex situ normothermic machine perfusion (NMP) is increasingly used for viability assessment of high‐risk donor livers, whereas dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia‐reperfusion injury. We aimed to resuscitate and test the viability of initially‐discarded, high‐risk donor livers using sequential DHOPE and NMP with two different oxygen carriers: an artificial hemoglobin‐based oxygen carrier (HBOC) or red blood cells (RBC). In a prospective observational cohort study of 54 livers that underwent DHOPE‐NMP, the first 18 procedures were performed with a HBOC‐based perfusion solution and the subsequent 36 procedures were performed with an RBC‐based perfusion solution for the NMP phase. All but one livers were derived from extended criteria donation after circulatory death donors, with a median donor risk index of 2.84 (IQR 2.52‐3.11). After functional assessment during NMP, 34 livers (63% utilization), met the viability criteria and were transplanted. One‐year graft and patient survival were 94% and 100%, respectively. Post‐transplant cholangiopathy occurred in 1 patient (3%). There were no significant differences in utilization rate and post‐transplant outcomes between the HBOC and RBC group. Ex situ machine perfusion using sequential DHOPE‐NMP for resuscitation and viability assessment of high‐risk donor livers results in excellent transplant outcomes, irrespective of the oxygen carrier used.
... Optimal utilization of grafts from DCD donors is most likely to have been associated with a learning curve 9 . More recent publications from countries outside the UK describe improvements in the use of DCD livers, including improved patient and graft survival and lower rates of biliary complications, PNF, and HAT [11][12][13][14][15] . A recent analysis of the UK liver transplant waiting list indicated that patients fair better by accepting an offer of a DCD liver rather than waiting for a future offer of a better-quality donor liver 16 . ...
Background
Despite high waiting list mortality rates, concern still exists on the appropriateness of using livers donated after circulatory death (DCD). We compared mortality and graft loss in recipients of livers donated after circulatory or brainstem death (DBD) across two successive time periods.
Methods
Observational multinational data from the United Kingdom and Ireland were partitioned into two time periods (2008–2011 and 2012–2016). Cox regression methods were used to estimate hazard ratios (HRs) comparing the impact of periods on post-transplant mortality and graft failure.
Results
A total of 1176 DCD recipients and 3749 DBD recipients were included. Three-year patient mortality rates decreased markedly from 19.6 per cent in time period 1 to 10.4 per cent in time period 2 (adjusted HR 0.43, 95 per cent c.i. 0.30 to 0.62; P < 0.001) for DCD recipients but only decreased from 12.8 to 11.3 per cent (adjusted HR 0.96, 95 per cent c.i. 0.78 to 1.19; P = 0.732) in DBD recipients (P for interaction = 0.001). No time period-specific improvements in 3-year graft failure were observed for DCD (adjusted HR 0.80, 95% c.i. 0.61 to 1.05; P = 0.116) or DBD recipients (adjusted HR 0.95, 95% c.i. 0.79 to 1.14; P = 0.607). A slight increase in retransplantation rates occurred between time period 1 and 2 in those who received a DCD liver (from 7.3 to 11.8 per cent; P = 0.042), but there was no change in those receiving a DBD liver (from 4.9 to 4.5 per cent; P = 0.365). In time period 2, no difference in mortality rates between those receiving a DCD liver and those receiving a DBD liver was observed (adjusted HR 0.78, 95% c.i. 0.56 to 1.09; P = 0.142).
Conclusion
Mortality rates more than halved in recipients of a DCD liver over a decade and eventually compared similarly to mortality rates in recipients of a DBD liver. Regions with high waiting list mortality may mitigate this by use of DCD livers.
... www.nature.com/scientificreports/ morbidities associated with cDCD livers [30][31][32][33] . A recent multicenter study suggests that use of postmortem NRP in cDCD donors may reduce rates of post-OLT BCs and graft loss 34 . ...
Controversy exists regarding whether the rate of hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) differs when using livers from donation after controlled circulatory death (DCD) versus livers from donation after brain death (DBD). The aim of this cohort study was to analyze rates of HCC recurrence, patient survival, and graft survival after OLT for HCC, comparing recipients of DBD livers (n = 103) with recipients of uncontrolled DCD livers (uDCD; n = 41). No significant differences in tumor size, tumor number, serum alpha-fetoprotein, proportion of patients within Milan criteria, or pre-OLT bridging therapies were identified between groups, although the waitlist period was significantly shorter in the uDCD group (p = 0.040). HCC recurrence was similar between groups. Patient survival was similar between groups, but graft survival was lower in the uDCD group. Multivariate analysis identified recipient age (p = 0.031), pre-OLT bridging therapy (p = 0.024), and HCC recurrence (p = 0.048) as independent risk factors for patient survival and pre-OLT transarterial chemoembolization (p = 0.045) as the single risk factor for HCC recurrence. In conclusion, similar patient survival and lower graft survival were observed in the uDCD group. However, the use of uDCD livers appears to be justified due to a shorter waitlist time, and lower waitlist dropout and HCC recurrence rates.
... On the basis of previous reports about the transplantation of livers obtained from donors after circulatory death, we presumed an incidence of 29% among livers that had been preserved by static cold storage, and we expected that the incidence with machine perfusion would be 11% (proportional reduction, 60%). [22][23][24][25] On the basis of a power of 80% and a 5% significance level (two-sided test) in two independent groups, we calculated that 77 livers would be needed in each trial group. We aimed to include 1 additional patient per trial group, resulting in 78 patients per group. ...
Background
Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited.
Methods
In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications.
Results
A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval [CI], 0.14 to 0.94; P=0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups.
Conclusions
Hypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.)
... The use of Maastricht categories I and II for DCD LTx has opened a potentially significant donor pool not previously utilized. However, this comes at the cost of a higher incidence of post-DCD LTx complications, such as ischemic type biliary lesions, primary non-function, and increased re-transplantation rates, in comparison to organs from DBD donors [4,[10][11][12]. ...
Introduction:
Liver transplantation is established as a lifesaving procedure for patients with acute and chronic liver failure, as well as certain selected malignancies. Due to a continuing 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 “supply and demand”.
Methods:
A retrospective analysis of DCD and subsequent liver transplantations was performed.
Results:
From May 2016 to September 2019, a total 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.
Conclusion:
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.
... Post-transplant cholangiopathies continue to be a major challenge in clinical liver transplantation, in terms of morbidity and mortality. Incidence rates range between 1 and 30%, depending on variations in ischemia times and donor variables (Abt et al., 2003;Dubbeld et al., 2010). After cold ischemic preservation, up to 90% of the donor livers present with histological evidence of luminal epithelium injury of the extrahepatic and large intrahepatic bile ducts (op den Dries et al., 2014). ...
Introduction
Chimerism after orthotopic liver transplantation (OLT) has largely been investigated in intrahepatic cellular constituents. However, little is known about chimerism in the extrahepatic and large intrahepatic bile ducts. Our aim was to evaluate the presence and extent of chimerism after OLT in the peribiliary glands (PBG) and the luminal epithelium of the large donor bile ducts.
Methods
For this study, we examined six extrahepatic and large intrahepatic bile ducts from livers that were re-transplanted. In all cases there was a sex-mismatch between donor and recipient (female donor organ and male recipient), which allowed to discriminate between donor- and recipient-derived cells. Specimens from female to female transplants were used as negative controls and male to male transplants as positive controls. Fluorescence in situ hybridization (FISH) for Y and X chromosomes was performed and the percentage of XY positive cells was determined among biliary epithelial cells. Immunohistochemistry was used to correlate chimerism with histological features.
Results
Cholangiocellular chimerism in all studied specimens ranged from 14 to 52%. The degree of chimerism was not associated with biliary damage. Marked chimerism was present at 5 days post-OLT. Ki-67-positivity was detected in 1–8% of the epithelial cells at the time of liver re-transplantation, and this correlated inversely with the degree of chimerism.
Conclusion
Recipient-derived cholangiocytes are present in the large bile ducts of the donor liver after OLT. The presence of chimerism in the large bile ducts suggests that recipient-derived cells may play a role in biliary regeneration following ischemia-induced injury during OLT.
... Initial reports examining the use of liver grafts from donation after circulatory death (DCD) donors described inferior long-term outcomes when compared to donation after brain death (DBD) donors as the result of high rates of biliary complications, increased rates of primary nonfunction (PNF), and hepatic artery thrombosis. [1][2][3][4][5] However, with increasing collective experience with DCD LT, national results have improved, 6 with multiple individual centers demonstrating similar outcomes between DCD and DBD LT. [7][8][9][10][11][12] The obesity epidemic has led to a rise in the number of steatotic donor liver grafts. There is a paucity of data on the outcome of DCD LT utilizing livers with macrosteatosis. ...
Background
Given the potentially additive risk from using donor livers that are both steatotic and from a donation after circulatory death(DCD) donor, there is a paucity of data on the outcome of DCD liver transplantation(LT) utilizing livers with macrosteatosis.
Methods
All DCD LT performed at Mayo Clinic‐Florida, Mayo Clinic‐Arizona and Mayo Clinic‐Rochester from 1999‐2019 were included(N=714). Recipients of DCD LT were divided into 3 groups: those with Moderate Macrosteatosis(30‐60%), Mild Macrosteatosis(5‐30%) and No Steatosis.
Results
Patients with Moderate Macrosteatosis had a higher rate of post‐reperfusion syndrome (PRS)(53.9% vs. 26.2%;p=0.002), post‐reperfusion cardiac arrest(7.7% vs.0.3%;p<0.001), primary non‐function(PNF)(7.7%vs.1.0%;p=0.003), early allograft dysfunction(EAD)(70.8%vs.45.6% and 8.3%;p=0.02) and acute kidney injury (AKI)(39.1%vs.19.4%; p=0.02) than patients with No Steatosis. No difference in any of the peri‐operative complications was seen between the Mild Macrosteatosis and the No Steatosis groups except for the rate of EAD(56.8%vs.45.6%;p=0.04). No difference in ischemic cholangiopathy(IC), vascular thrombosis/stenosis or graft and patient survival was seen between the three groups.
Conclusion
DCD donors with mild macrosteatosis <30% can be utilized with no increase in peri‐operative complications and similar patient and graft survival compared to DCD donors with no steatosis. When utilizing DCD donors with moderate macrosteatosis higher rates of PRS, PNF, post‐reperfusion cardiac arrest, EAD and AKI should be anticipated.
... 1,2 Nevertheless, recent studies have displayed similar graft and recipient survival outcomes following DCD-LT compared with livers transplanted from DBD donors. [3][4][5][6] Several studies have been designed to identify risk factors in DCD-LT. Different donor factors, such as age, weight, or body mass index (BMI), procedure-related factors such as cold ischemia time (CIT) or warm ischemia time (WIT), or recipient model for end-stage liver disease (MELD) scores have been significantly associated with graft failure after DCD-LT. ...
Background:
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 ischaemic cholangiopathy (IC), and to compare these results with those of LT using DBD in the same time period.
Methods:
Between June 2012 and July 2018, we performed 66 transplants using cDCD and 258 with DBD grafts.
Results:
The incidence of IC was similar in both groups (2% in DBD, 1.5% in DCD; p=0.999). No significant differences were found for overall graft and patient survival rates between the groups at 1 and 2 years post-transplantation.
Conclusions:
This study provided evidence that cDCD donors exhibit excellent graft and patient survival outcomes. When the warm ischaemia time is less than 30 minutes and cold ischaemia time is less than 6 hours, 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.
... These disadvantages were reported at the onset of controlled-DCD programs along with worse graft and patient survival rates. 6,7 Currently, the results can be comparable to those obtained with DBD, 8 but the percentage of potential grafts rejected during the evaluation and extraction process can reach 30% to 40% of the total potential donors evaluated. The most frequent cause of rejection of a DCD graft is the presence of a poor macroscopic aspect at recovery. ...
Our main objective was to compare liver transplantation (LT) results between donation after circulatory death (DCD) and donation after brainstem death (DBD) in our hospital and to analyze, within the DCD group, the influence of age on the results obtained with DCD donors with ages over 70 years and up to 80 years. All DCD‐LT performed were analyzed prospectively. The results of the DCD group were compared with those of a control group who received a DBD‐liver transplant immediately after each DCD‐liver transplant. Later, the results obtained within the DCD group were analyzed according to the age of the donors, considering 2 subgroups with a cut‐off point at 70 years. Survival results for liver transplantation with DCD and super rapid recovery (SRR) were not inferior to those obtained in a similar group of patients transplanted with DBD livers. However, the price of DCD was a higher rate of biliary complications, including ischemic cholangiopathy. Donor age was not a negative factor. This article is protected by copyright. All rights reserved.
Exposure to vaccine lipid nanoparticles, mRNA, adenoviral DNA, and or Spike protein from one of the approved Covid-19 vaccines, or through secondary exposure, as through blood transfusion, is a potential source of harm. Blood reactions are an acknowledged side-effect of Covid-19 vaccination, not limited to hemolysis, paroxysmal nocturnal hemoglobinuria, chronic cold agglutinin disease, immune thrombocytopenia, haemophagocytosis, hemophagocytic lymphohistiocytosis, and many other blood related conditions. The observation of adverse events has motivated investigation into the cardiovascular mechanisms of harm by Covid-19 vaccines, and the biodistribution of vaccine contents. Biodistribution may not be limited to the body of the vaccine recipient, as a growing body of evidence demonstrates the possibility of secondary exposure to vaccine particles. These can be via bodily fluids and include the following routes of exposure: blood transfusion, organ transplantation, breastfeeding, and possibly other means. As covid-19 vaccines are associated with an increased risk of stroke, the persistence of vaccine artifacts in the blood presents a possible threat to a recipient of a blood donation from a vaccinated donor who suffered from vaccine induced thrombosis or thrombocytopenia. (VITT) We assess the feasibility and significance of these risks through an overview of the case report literature of blood disorders in vaccinated individuals, pharmacovigilance reports from the US Vaccine Adverse Events Reporting System (VAERS) and a meta-analysis of the available literature on organ transplants from vaccinated organ donors. Our analysis establishes biological mechanistic plausibility, a coherent safety signal in pharmacovigilance databases for secondary vaccine contents exposure (for the cases of blood transfusion and breastfeeding) and also an elevated level of adverse events in organ transplants from VITT-deceased donors, echoing increases in organ transplantation related complications seen in national statistics for some countries. Secondary exposure to vaccine artifacts is a potential explanation for some of the cases put forth, and requires a deeper investigation.
Relevance. The choice of biliary anastomosis is the main factor determining the risk of developing biliary complications after orthotopic liver transplantation. The two most common forms of biliary tract reconstruction are choledocholedochostomy (duct-to-duct anastomosis) and choledochoeunostomy (connection of the bile duct to the jejunum). The choice of biliary tract reconstruction is determined by a variety of factors, including the underlying pathology of the liver, the size of the bile ducts of the donor and recipient, previous transplantation or previous biliary tract surgery, as well as the preferences of the surgeon performing the operation. Despite the correctly chosen method of reconstruction, complications such as strictures, lithiasis, biloma, and bile leakage occur infrequently.
Objective : to present a review of the literature on methods of diagnosis and treatment of biliary complications after liver transplantation.
Materials and methods . The analysis of literary sources in English and Russian from 2010 to 2023 on this topic in the databases PubMed, MEDLINE, Google Scholar was carried out. The review highlights clinical studies, as well as literature reviews on similar topics with an emphasis on the treatment and diagnosis of biliary complications.
Conclusion. The problem of biliary complications of liver transplantation remains relevant and unresolved to the end. Noninvasive imaging techniques for complications arising after biliary tract surgery have prospects for development. The tactics of percutaneous, endoscopic and open interventions on the biliary graft tree require further improvement.
Background:
Normothermic machine perfusion (NMP) is used for the viability assessment of high-risk donor livers before transplantation. The production of hemostatic proteins is one of the major synthetic functions of the liver. The objective of this study was to measure the concentration and functionality of hemostatic proteins concentration in the NMP perfusate of human donor livers.
Methods:
Thirty-six livers that underwent NMP for viability assessment were included in this study. Perfusate samples taken during NMP (start, 150 min, and 300 min) were used for the measurement of antigen and activity levels of hemostatic proteins (factors II, VII, and X; fibrinogen; plasminogen; antithrombin; tissue plasminogen activator; von Willebrand factor; and proteins induced by vitamin K absence). The antigen levels were correlated with hepatocellular function according to previously proposed individual hepatocellular viability criteria: lactate clearance and perfusate pH.
Results:
Antigen levels of hemostatic proteins reached subphysiological levels in the NMP perfusate. Hemostatic proteins that were produced during NMP were at least partially active. All livers produced all hemostatic proteins tested within 150 min of NMP. Hemostatic protein concentrations did not significantly correlate with perfusate lactate and perfusate pH after 150 min of NMP.
Conclusions:
All livers produce functional hemostatic proteins during NMP. The generation of a functional hemostatic system in NMP perfusate confirms the need for adequate anticoagulation of the perfusate to avoid generation of (micro)thrombi that may harm the graft.
The current shortage of pediatric multivisceral donors accounts for the long time and mortality on the waiting list of pediatric patients. The use of donors after cardiac death, especially after the outbreak of normothermic regional perfusion, has increased in recent years for all solid organs except the intestine, mainly because of its higher susceptibility to ischemia-reperfusion injury. We present the first literature case of multivisceral donors after cardiac death transplantation in a 13-month-old recipient from a 2.5-month-old donor. Once exitus was certified, an extracorporeal membrane oxygenation circuit was established, cannulating the aorta and infrarenal vena cava, while the supra-aortic branches were clamped. The abdominal organs completely recovered from ischemia through normothermic regional perfusion (extracorporeal membrane oxygenation initially and beating heart later). After perfusion with the preservation solution, the multivisceral graft was uneventfully implanted. Two months later, the patient was discharged without any complications. This case demonstrates the possibility of reducing the time spent on the waiting list for these patients.
Introduction
Donation after cardiac death (DCD) has been leading the way to help bridge the growing gap between availability of donors and recipients on waitlist. With advances in technology and our understanding of DCD donation the safety profile is growing. It is becoming an increasing viable option even in marginal settings.
Discussion
The ethos surroundings DCD is still a matter of contention but there is support and collaboration from larger societies and establishments with development of standardizing protocols. Preparation is key. Experience of the procurement and transplanting surgeons are pivotal. There are multiple moving parts and for the success of a DCD program, dedication is needed from the donor hospitals, organ procurement organizations and the transplant centers. Previous practices based on anecdotal experiences are now either supported by or refuted by increasing evidence and data, based on the development of consensus-based guidelines with the end goal of having uniform outcomes. Normothermic regional and machine perfusion have expanded options in the DCD world, challenging the limits and expanding our paradigm. Recognition of the weaknesses and organ specific complications allow the clinician to make choices for optimal outcomes. These advancements have allowed outcomes to be optimized.
Conclusions
Expanding the organ donor pool is one solution to increase the availability of organs for transplantation. Increasing the attention to and the use of DCD organs combined with machine and normothermic perfusion is a future strategy to obtain ongoing clinical success in organ transplantation and lower the waiting list mortality.
Liver transplantation from donors after circulatory death (DCD) is associated with considerable rates of primary nonfunction and ischemic-type biliary lesions. Compared with donation was after brain death (DBD), the biggest disadvantage of DCD is warm ischemia injury in the procurement stage. Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. Such donors should donate according to the DCD procedure, that is, remove life support and donate after cardiac arrest. We retrospectively analyzed donor and recipient characteristics with preoperative and postoperative parameters according to 3 donation types to comprehensively describe incidence of ischemia reperfusion injury (IRI) related biliary complications among different donor type adult liver transplantation recipients. A total of 50 patients were included in this study (DBD group n = 17, DCD group n = 26, DBCD group n = 7). Only 1 patient, whose donor type was DBCD was diagnosed with ischemic-type biliary lesions demonstrated cast and retrograde ascending cholangitis. Rates of primary graft non-function (DBD n = 1, 5.9%; DCD n = 2, 7.7%; DBCD, 0%; P = .546) were similar and total biliary complications (DBD n = 1, 5.9%; DCD n = 1, 3.8%; DBCD N = 2, 28.6%; P = .042) were different. No differences were found regarding development of postreperfusion syndrome or coagulopathy in 3 groups. Compared with standard DBD donor, the clinical outcome of DCD donor liver transplantation was satisfactory, with no increase in the incidence of IRI, and, no difference in the incidence of ischemic bile duct complications. This work was carried out in compliance with the Helsinki Congress and the Declaration of Istanbul.
Background
An increased number of older recipients underwent liver transplantation in recent years, and consequently needing to obtain more liver grafts. In order to increase this pool, in 2006, we initiated the use of livers from uncontrolled circulatory death (uDCD). We analyzed the use of uDCD livers in sexagenarian recipients and their effect on overall survival.
Methods
A retrospective and comparative study was performed among 4 groups according to recipient age (less or greater than 60 years) and donor type (donor brain death [DBD] or uDCD): Group A: DBD livers in recipients aged <60 years (n = 169); Group B: uDCD livers in recipients aged <60 years (n = 36); Group C: DBD livers in recipients aged >60 years (n = 96); and Group D: uDCD livers in recipients aged >60 years(n = 39).
Results
Intraoperative transfusion, biliary complications, primary non-function, acute rejection, chronic renal dysfunction, retransplantation, and mortality during follow-up (cardiovascular diseases in 3 patients, hepatitis C virus recurrence in 4 patients, and de novo malignancies in 3 patients) were significantly higher, and 5-year patient and graft survival was significantly lower in sexagenarian recipients.
Bilirubin and packed red blood cells transfusion were risk factors for patient survival, whereas hepatocelular carcinoma, creatinine, and packed red blood cells transfusion were risk factors for patient survival. Recipient age (<60 years) was confirmed as protective factor for patient and graft survival, whereas the use of uDCD was not a risk factor for patient or graft survival.
Conclusions
Use of a uDCD liver did not demonstrate as a risk factor for patient and graft survival, and recipient age (<60 years) was a protective factor for patient and graft survival.
Introduction and Objectives
Outcomes of liver transplantation (LT) with donors after circulatory death (DCD) have been considered suboptimal due to higher rates of ischemic cholangiopathy, especially when the super-rapid recovery (SRR) technique is used. This study aimed to compare the incidence of complications between recipients receiving DCD vs those receiving donors after brain death (DBD) in a large-volume liver transplant centre.
Methods
We performed a retrospective cohort study (LT from January 2015 to December 2018) comparing recipients who underwent a LT with DCD vs. a control group of LT with DBD, matched 1:1 without replacement by propensity score matching that included the following variables: LT indication, recipient sex and age, donor age and MELD score.
Results
51 recipients with DCD-LT (29 SRR, 22 normothermic regional perfusion [NRP]) were matched with 51 DBD-LT recipients. Biliary complications were more frequent in DCD, 10%(n=5), all with SRR technique, vs 2%(n=1) in the DBD group, p=0.2}. Two patients (4%) suffered primary graft non-function in the DCD group (1 SRR and 1 NRP) versus zero in the DBD group (p=0.49). Postoperative bleeding and reinterventions were also higher in the DCD group: 7 (13.7%) vs 1 (1.95%) and 8 (15.7%) vs 2 (3.9%) respectively (p=0.06 and 0.09). On the 1st postoperative day AST/ALT peak was higher in DCD (p≤0001). The incidence of rejection, vascular complications, renal injury, hospital stay, and readmissions were similar in both groups. Cumulative 1-, 2-, 3- and 4-year graft and patient survival were also similar.
Conclusions
DCD donors are an adequate option to increase the donor pool in LT, achieving similar graft and patient survival rates to those achieved with DBD donors, especially when the NRP technique is used.
Liver transplantation (LT) is the only curative therapy in patients with end-stage liver disease with excellent long-term survival; however, LT recipients are at risk of significant complications. Among these complications are biliary complications with an incidence ranging from 5 to 32% and associated with significant post-LT morbidity and mortality. Prompt recognition and management are critical as these complications have been associated with mortality rates up to 19% and retransplantation rates up to 13%. An important limitation of published studies is that a large proportion does not discriminate between anastomotic strictures and nonanastomotic strictures. This review aims to summarize our current understanding of risk factors and natural history, diagnostic testing, and treatment options for post-LT biliary strictures.
DCD donor is a valuable organ source for liver transplantation, which is helpful to reduce the mortality of patients with end-stage liver disease and increase the availability of organ transplantation. The future development prospect of DCD liver transplantation is good [1]. With the continuous improvement of surgical skills and relevant clinical assistant techniques for DCD liver transplantation, its clinical effects have been continuously improved, but generally speaking, it is still not as good as donation after brain death (DBD) liver transplantation. The survival rate of patients after DCD liver transplantation at 1 and 3 years was lower than that of DBD liver transplantation, and the incidence of postoperative complications was higher than that of DBD liver transplantation. DCD graft is prone to postoperative complications such as ischemic bile duct stricture, primary graft nonfunction, hepatic artery, and portal vein thrombosis [2, 3].
As the demand for organ transplantation increases, utilization of liver allografts of donation after cardiac death (DCD) is becoming increasingly necessary. Although, the clinical outcomes of DCD allografts have been well described, the histologic features are not well characterized. Liver biopsies (n=131) from age matched DCD (n=60) and donation after brain death (DBD; n=71) recipients with Hepatitis C virus were compared. Histologic features were studied in a blinded fashion, subgrouped into time 0, 0-6 months, and >6 months. In time 0 biopsies, more DCD cases had zone 3 (43.8 vs 29%) and bridging necrosis (19 vs 0%), albeit not statistically significant. At 0-6 months, more DCD cases had portal edema (p=0.01). Pericholangitis (30.4% vs 18.8%) and acute cholestasis (21.7% vs 12.5%) were more common in DCD, but not statistically significant. At >6 months, pericholangitis (19% vs 4.5%) persisted in DCD, though not statistically significant. Overall, both groups had similar bile duct injury, portal inflammation, and fibrosis. Post-operative biliary complications were more common in DCD (19% vs 0%). 3-year and 10-year graft survival and patient outcomes were similar in both cohorts. Biliary alterations were more prevalent in the 0-6 month time period DCD biopsies reflecting increased vulnerability of this group to biliary complications in the early post-OLT period. This finding may suggest poor graft perfusion despite comparable cold ischemia times. However, these features improved and DCD recipients have similar graft and overall survival compared to DBD recipients indicating that carefully selected DCD liver allografts are a viable option for transplantation.
Background
Donation after circulatory death (DCD) is related to a warm ischemia time and more complications compared with traditional donors (donation after brain death [DBD]).
Methods
This study included biopsy samples retrospectively collected from November 2014 to December 2018 to compare histologic and biological markers of DCD and DBD liver grafts. The analysis includes marker of early apoptosis (p21), senescence (telomerase reverse transcriptase [TERT]), cell damage (caspase-3 active), endothelial damage (vascular endothelial growth factor), stem cell (CD90), hypoxia (HIF1A), inflammatory activation (COX-2), and cross-organ allograft rejection (CD44). A propensity score matching (PSM) was used to match patients receiving DCD livers to those receiving DBD livers. We analyzed the immunohistochemical initial liver damage–related warm ischemia time.
Results
Positive staining expression of liver damage biomarkers (COX-2, CD44, TERT, HIF1A, and CD90) was found, but no significant differences were found between DCD and DBD and with ischemic cholangiopathy. After PSM, there was a significant relationship between CD90 and male donors (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.07-0.91), TERT with donor sodium (OR, 1.11; 95% CI, 1.02-1.2), HIF1A with steatosis (OR, 0.33; 95% CI, 0.13-0.83), and CD44 with donor vasoactive drugs (OR, 0.36; 95% CI, 0.13-1) and glutamic oxaloacetic transaminase 1 week increase (OR, 1.01; 95% CI, 1-1.03).
Conclusions
DCD immunohistochemical initial liver damage was found to behave similarly to DBD. The increase in complications and cholangiopathy associated with warm ischemia could be related to a different later phenomenon.
Although the utilization of donation after circulatory death donors (DCDs) for liver transplantation (LT) has increased steadily, much controversy remains, and no common acceptance criteria exist with regard to donor and recipient risk factors and prediction models. A consensus conference was organized by International Liver Transplantation Society on January 31, 2020, in Venice, Italy, to review the current clinical practice worldwide regarding DCD-LT and to develop internationally accepted guidelines. The format of the conference was based on the grade system. International experts in this field were allocated to 6 working groups and prepared evidence-based recommendations to answer-specific questions considering the currently available literature. Working group members and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and recommendations provided by working group 2, covering the entire spectrum of donor and recipient risk factors and prediction models in DCD-LT.
Livers for transplantation from donation after circulatory death donors are relatively more prone to early and ongoing alterations in graft function that might ultimately lead to graft loss and even patient death. In consideration of this fact, this working group of the International Liver Transplantation Society has performed a critical evaluation of the medical literature to create a set of statements regarding the assessment of early allograft function/dysfunction and complications arising in the setting of donation after circulatory death liver transplantation.
Controversy exists regarding whether the rate of hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) differs when using livers from donation after controlled circulatory death (DCD) versus livers from donation after brain death (DBD).
The aim of this cohort study was to analyze rates of HCC recurrence, patient survival, and graft survival after OLT for HCC, comparing recipients of DBD livers (n=103) with recipients of uncontrolled DCD livers (uDCD; n=41).
No significant differences in tumor size, tumor number, serum alpha-fetoprotein, proportion of patients within Milan criteria, or pre-OLT bridging therapies were identified between groups, although the waitlist period was significantly shorter in the uDCD group (p=0.04). HCC recurrence was similar between groups. Patient survival was similar between groups, but graft survival was lower in the uDCD group. Multivariate analysis identified recipient age (p=0.03), pre-OLT bridging therapy (p=0.02), and HCC recurrence (p=0.04) as independent risk factors for patient survival and pre-OLT transarterial chemoembolization (p=0.04) as the single risk factor for HCC recurrence.
In conclusion, similar patient survival and lower graft survival were observed in the uDCD group. However, the use of uDCD livers appears to be justified due to shorter waitlist time and similar HCC recurrence in both groups.
Machine perfusion technology has been revolutionizing the field of liver transplantation and undergoes rapid clinical implementation. But what is machine perfusion? Why should we implement this? And how can machine perfusion be responsible for increases in the quality and quantity of liver transplants? The concept of machine perfusion is relatively simple; it provides an environment for the liver graft outside of the body while closely mimicking the physiologic in-vivo situation. The liver is connected via its blood vessels to a sterile machine perfusion device and an adjustable continuous flow of perfusate through the liver is generated. With this, machine perfusion offers the ability to better preserve donor liver grafts while providing oxygen and nutrients, for reconditioning and optimization of liver grafts. During machine perfusion the accumulated oxygen and nutrient debts can be restored, and normal repair and regenerative pathways can be re-activated. The liver, with its energy stores and metabolic state replenished, is preconditioned and better prepared for the injurious effects of reperfusion injury after implantation in the recipient, especially the livers of suboptimal quality. Besides that, machine perfusion allows for ex-situ real-time assessment of viability prior to transplantation. This may potentially increase the donor pool as previously discarded suboptimal liver grafts can be tested for viability and subsequently transplanted if viable. Finally, machine perfusion may facilitate longer ex-situ storage of donor organs, which facilitates logistics of transplant procedures. Altogether, with an increasing demand for liver grafts worldwide, machine perfusion promises to be a beneficial alternative preservation method for liver grafts, especially those considered to be of suboptimal quality.
Donation after circulatory death (DCD) donors are a unique group of patients who do not fulfil the conventional classification of brain death but in whom further resuscitation or treatment is considered futile. Once cardiac arrest and the cessation of circulation has been confirmed, either due to unsuccessful resuscitation or planned withdrawal of treatment they can proceed to organ donation. Donation is performed by rapidly preserving and cooling the organs followed by surgical removal. Since the advent of early kidney only DCD programmes, successful liver, pancreas, lung and heart DCD protocols have been developed and translated into clinical practice. Despite good outcomes following transplant with DCD organs there are additional risks, including higher rates of primary non-function (kidney, liver) and delayed graft function (kidney). However, this has stimulated research into improving outcomes by better donor selection, improved preservation and utilisation of technology. In particular, hypothermic and normothermic machine perfusion of kidneys, livers, hearts and lungs has been driven by the increase in DCD donors and a desire to optimise outcomes and minimise organ discard.
Purpose
To evaluate whether Doppler ultrasonography (DUS) and contrast-enhanced ultrasonography (CEUS) can identify liver donation after brain death (DBD) and cardiac death (DCD) with the risk of developing short-term primary graft dysfunction (PGD) or arterial and biliary complications within 1 year.
Materials and methods
Consecutive DBD and DCD donors who underwent DUS/CEUS examinations before surgical procurement from February 2016 to June 2018 at our institution were included. The US and CEUS images of each donor liver were analysed, and the parameters were recorded.
Results
The mean time for US examination was 32 min (range, 20-59 min), and all donors tolerated the examination well. In terms of short-term outcomes, among the 52 eligible donor livers, 20 (38.5%) of their recipients developed PGD. The multivariable analysis showed that decreased enhancement of donor livers on CEUS (OR = 15.976, 95% CI: 1.652-154.628, P = 0.017) and high recipient model for end-stage liver disease (MELD) scores (OR = 1.050, 95% CI: 1.004-1.099, P = 0.034) before liver transplantation (LT) were independent factors of PGD. In contrast, for long-term complications, among the 48 eligible donor livers, 16 (33.3%) developed arterial or biliary complications within 1 year. The multivariable analysis did not show any independent factors of arterial or biliary complications within 1 year.
Conclusions
A decrease in enhancement on CEUS is an independent risk factor for poor short-term outcomes of LT. CEUS may be promising for predicting post-LT outcomes of critically ill donors effectively and safely by evaluating the haemodynamic changes in DBD and DCD donor livers.
Better understanding of how to utilize donation after circulatory death (DCD) liver grafts has resulted in improved national outcomes and expansion in the number of DCD liver transplants (LTs). This improvement has been driven by better donor and recipient matching, careful evaluation of hemodynamics during withdrawal of life support, and refinement of the procurement operation. Changes to liver allocation likely will result in increased utilization of DCD liver grafts. Ischemic cholangiopathy remains the Achilles heel of DCD LTs and, although rates have fallen with improved protocols, a certain rate likely is unavoidable. This review discusses contemporary issues with DCD LTs.
Background
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).
Methods
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 11 years.
Results
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 >3700 ml/min as protective effect.
Conclusions
Adequate donor pump flow during NRP was a protective.
AnaesthesiaAnaesthesia for liver transplantationLiver transplantation (LT) is still challenging due to the potential forhaemodynamicHaemodynamic instability during reperfusionReperfusion, massive blood lossBlood loss, pro- and anti-coagulant factor imbalance, massive fluidFluids replacement and fluid shift, all organ impairment, severe cardiovascular events, rapid deterioration and marginal grafts. There is no official training program for LT anaesthetists, and different countries have different ways of preparing anaesthetists for safe LT anaesthesia delivery. The fact that there are numerous publications on anaesthesia indicates that this speciality is very complex. Therefore, this chapter aims to simplify and explain the basics of LT anaesthesia and should be read alongside all of the other chapters in the LT section.
The increasing utilization of extended criteria donors (ECD) to overcome the demand of liver grafts and decrease the mortality on the waiting list for transplant, has led the transplant community to explore alternative preservation techniques to minimise the ischaemia reperfusion injury (IRI) associated to ECD, decrease the risk of complications and achieve similar outcomes. These new alternative preservation techniques have emerged in recent years, involving ex situ but also in situ machine perfusion, and it is predicted that it may become the standard of care in the near future. The advantage of these techniques is that they can preserve and provide oxygen to the donor liver, they can recondition and improve the donor organ quality, and in normothermic conditions they can provide a functional assessment and viability of the graft to help the surgeons in the decision making whether to utilize that liver. Other advantages are the potential to improve transplant logistics with prolonged preservation times and also the possibility of using therapeutic strategies during the perfusion to improve their quality or further minimise IRI. Current research is being undertaken using these different perfusion techniques alone or in combination to minimize the ischemic damaged suffered during procurement and cold preservation of the donor livers, to increase the donor pool and decrease the discard rates of ECD livers that could be safely transplanted.
Background:
Biliary complications are the most common complications of donation after circulatory death (DCD) liver transplantation and the international experience with DCD transplants suggests increased rates of biliary complications compared to donation after brain death transplants. Therefore, it is important to understand factors that are associated with the development of biliary complications within the Australian DCD context in order to inform future practice. The aim of this study is to determine the incidence of biliary complications after DCD liver transplantation at the Australian National Liver Transplantation Unit and identify factors associated with this outcome.
Methods:
A retrospective analysis of all adult DCD liver transplants at the Australian National Liver Transplantation Unit from 2007 to 2015 was undertaken. The primary outcome measure was the incidence of biliary complications and was censored on 31 December 2016. Recipients were then stratified into groups based on the development of biliary complications and risk factor analysis was performed.
Results:
Biliary complications occurred in 35% of DCD transplants, including seven anastomotic strictures and 10 non-anastomotic strictures. Higher donor risk index scores (P = 0.03), post-transplant portal vein complications (P = 0.042) and peak gamma-glutamyl transferase levels within 7 days post-transplant (P = 0.047) were associated with biliary complications.
Conclusion:
Findings from this study demonstrate that biliary complications remain common in DCD liver recipients. Recipients who developed a biliary complication tended to have higher donor risk index, elevated peak gamma-glutamyl transferase levels within 7 days post-transplant or a portal vein complication. The presence of any of these factors should prompt close monitoring for post-transplant biliary complications.
Background
Living donor liver transplantation (LDLT) and donation after circulatory death (DCD) can expand the donor pool for cholestatic liver disease (CLD) patients. We sought to compare the outcomes of deceased donor liver transplant (DDLT) vs. LDLT in CLD patients.
Methods
Retrospective cohort analysis of adult CLD recipients registered in the OPTN database who received primary LT between 2002‐2018. Cox proportional hazards regression models with mixed effects were used to determine the impact of graft type on patient and graft survival.
Results
5,999 DDLT (5,730 donation after brain death [DBD], 269 DCD) and 912 LDLT recipients were identified. Ten‐year patient/graft survival rates were DBD:73.8%/67.9%, DCD:74.7%/60.7%, and LDLT:82.5%/73.9%. Higher rates of biliary complications as a cause of graft failure were seen in DCD(56.8%) than LDLT(30.5%) or DBD(18.7%) recipients. On multivariable analysis, graft type was not associated with patient mortality, while DCD was independently associated with graft failure (P =0.046).
Conclusion
DBD, DCD, and LDLT were associated with comparable overall patient survival. No difference in the risk of graft failure could be observed between LDLT and DBD. DCD can be an acceptable alternative to DBD with equivalent patient survival, but inferior graft survival likely related to the high rate of biliary complications.
Ischemic cholangiopathy (IC) has been described as the Achilles heel of donation after circulatory death (DCD) liver transplantation. Ischemic cholangiopathy can be defined as diffuse nonanastomotic biliary strictures that occur in a spectrum of clinical and radiologic severity following liver transplantation. Biliary ducts, especially cholangiocytes, seem to be more sensitive to ischemia than hepatocytes; however the exact mechanism for this is not entirely clear. While IC is observed as a complication of both donation after brain death (DBD) and DCD liver transplantation, initial series with DCD liver transplantation demonstrated IC rates as high as 30% compared to rates of 2–4% seen with DBD liver transplantation. Several distinct radiologic patterns of IC have been described, which are associated with different clinical courses; these include diffuse necrosis, bilateral multifocal/multifocal progressive, confluence dominant, and the minor form. Treatment of IC can be difficult given the often diffuse multifocal lesions of the biliary tree. Initial therapy primarily focuses on addressing biliary obstruction and treatment of infection (cholangitis). While milder cases of IC can sometimes be successfully managed with percutaneous or endoscopic drainage and stenting, more severe cases will often ultimately require retransplantation. The present chapter provides a thorough overview of IC and provides both proposed treatment options as well as preventative strategies.
Within the last decade, liver transplantation from DCD donors has gained interest and outcomes have improved, mainly due to an increased awareness of the overall risk and subsequent selection policy. Although most countries have steadily pushed their donor risk factor boundaries, the overall utilization rate of DCD livers remains suboptimal. The repeat occurrences of DCD-specific complications, difficult to reduce further, are highlighted as one reason behind such advancement standstill, despite the continuous technical, medical, and anesthesiologic innovation.
Donation after circulatory death (DCD) donors represent a potential means to help address the disparity between the number of patients awaiting liver transplantation (LT) and the availability of donor livers. While initial enthusiasm for DCD LT was high in the early 2000s, early reports of high rates of biliary complications and inferior graft survival resulted in reluctance among many transplant centers to use DCD liver grafts. As with all innovations in transplant practice, there is undoubtedly a learning curve associated with the optimal utilization of liver grafts from DCD donors. More contemporary data has demonstrated that results with DCD LT are improving and the number of DCD LT performed annually has been steadily increasing. In this concise review, potential mechanisms of injury for DCD livers are discussed along with strategies that have been employed in clinical practice to improve DCD LT outcomes.
Introduction
During conventional liver transplantation (CLT), ischaemia-reperfusion injury (IRI) is inevitable and is associated with complications such as early allograft dysfunction (EAD), primary non-function and ischaemic-type biliary lesions. We have established a novel procedure called ischaemia-free liver transplantation (IFLT). The results from a pilot study suggest that IFLT might prevent IRI and yield better transplant outcomes than CLT. The purpose of this study was to further assess the efficacy and safety of IFLT versus CLT in patients with end-stage liver disease.
Methods and analysis
This is an investigator-initiated, open-label, phase III, prospective, single-centre randomised controlled trial on the effects of IFLT in patients with end-stage liver disease. Adult patients (aged 18–75 years) eligible for liver transplantation will be screened for participation in this trial and will be randomised between the IFLT group (n=34) and the CLT group (n=34). In the IFLT group, the donor liver will be procured, preserved and implanted with continuous normothermic machine perfusion (NMP). In the CLT group, the donor liver will be procured after a fast cold flush, preserved in 0°C–4°C solution and implanted under hypothermic and hypoxic conditions. Patients in both groups will be managed according to the standard protocol of our centre. The primary end point is the incidence of EAD after liver transplantation. Intraoperative and postoperative parameters of donor livers and recipients will be observed and recorded, and postoperative liver graft function, complications and recipient and graft survival will be evaluated. After a 12-month follow-up of the last enrolled recipient, the outcomes will be analysed to evaluate the safety and efficacy of IFLT versus CLT in patients with end-stage liver disease.
Ethics and dissemination
The protocol was reviewed and approved by the Ethics Committee of The First Affiliated Hospital of Sun Yat-sen University. The findings will be disseminated to the public through conference presentations and peer-reviewed scientific journals.
Trial registration number
ChiCTR1900021158.
The utilization of livers from uncontrolled donor circulatory death (uDCD) donation increases the availability of liver grafts, but is associated with a higher incidence of biliary complications (BCs) and lower graft survival than those donated after brain death (DBD). From January 2006 to December 2016, we performed 75 orthotopic liver transplantations (OLT) using uDCD livers. To investigate the relationship of BCs with the use of uDCD OLT, we compared patients who developed BCs (23 cases) to those who did not (non‐BC, 43 cases) after excluding cases of primary nonfunction and hepatic artery thrombosis, a known cause of BC. The groups had similar uDCD donor maintenance, donor and recipient characteristics, and perioperative morbidity/mortality rates, but we observed a higher rate of hepatocellular carcinoma and hepatitis C virus in the non‐BC group. For BC management, percutaneous transhepatic biliary dilation was performed in 21 cases, endoscopic retrograde cholangiopancreatography dilation in 3 cases, Roux‐en‐Y hepaticojejunostomy in 6 cases, T‐tube in 1 case, and retransplantation in 3 cases. In the BC group, 1‐, 3‐, and 5‐year patient survival was 91.3%, 69.6%, and 65.2% versus 77.8%, 72.9%, and 72.9% in the non‐BC group (P=0.89), whereas 1‐, 3‐, and 5‐year graft survival was 78.3%, 60.9%, and 56.5% in BC group versus 77.8%, 72.9%, and 72.9% in the non‐BC group (P=0.38). Multivariate analysis did not indicate independent risk factors for BC development. Conclusion: Patient and graft survival was generally lower in patients who developed BCs, but not significantly so, and these complications were managed in the majority of patients through radiological, endoscopical, or Roux‐en‐Y hepaticojejunostomy. Retransplantation is necessary in rare cases, after the failure of biliary dilation or surgical procedures.
Objective:
The aim of this study was to evaluate sequential hypothermic and normothermic machine perfusion (NMP) as a tool to resuscitate and assess viability of initially declined donor livers to enable safe transplantation.
Summary background data:
Machine perfusion is increasingly used to resuscitate and test the function of donor livers. Although (dual) hypothermic oxygenated machine perfusion ([D]HOPE) resuscitates livers after cold storage, NMP enables assessment of hepatobiliary function.
Methods:
In a prospective clinical trial, nationwide declined livers were subjected to ex situ NMP (viability assessment phase), preceded by 1-hour DHOPE (resuscitation phase) and 1 hour of controlled oxygenated rewarming (COR), using a perfusion fluid containing an hemoglobin-based oxygen carrier. During the first 2.5 hours of NMP, hepatobiliary viability was assessed, using predefined criteria: perfusate lactate <1.7 mmol/L, pH 7.35 to 7.45, bile production >10 mL, and bile pH >7.45. Livers meeting all criteria were accepted for transplantation. Primary endpoint was 3-month graft survival.
Results:
Sixteen livers underwent DHOPE-COR-NMP. All livers were from donors after circulatory death, with median age of 63 (range 42-82) years and median Eurotransplant donor risk index of 2.82. During NMP, all livers cleared lactate and produced sufficient bile volume, but in 5 livers bile pH remained <7.45. The 11 (69%) livers that met all viability criteria were successfully transplanted, with 100% patient and graft survival at 3 and 6 months. Introduction of DHOPE-COR-NMP increased the number of deceased donor liver transplants by 20%.
Conclusions:
Sequential DHOPE-COR-NMP enabled resuscitation and safe selection of initially declined high-risk donor livers, thereby increasing the number of transplantable livers by 20%.
Trial registration:
www.trialregister.nl; NTR5972.
There is a lack of universally accepted clinical parameters to guide the utilization of donation after cardiac death (DCD) donor livers and it is unclear as to which patients would benefit most from these organs. We reviewed our experience in 141 patients who underwent liver transplantation using DCD allografts from 1993 to 2007. Patient outcomes were analyzed in comparison to a matched cohort of 282 patients who received livers from donation after brain death (DBD) donors. Patient survival was similar, but 1-, 5- and 10-year graft survival was significantly lower in DCD (69%, 56%, 44%) versus DBD (82%, 73%, 63%) subjects (p < 0.0001). Primary nonfunction and biliary complications were more common in DCD patients, accounting for 67% of early graft failures. A donor warm ischemia time >20 min, cold ischemia time >8 h and donor age >60 were associated with poorer DCD outcomes. There was a lack of survival benefit in DCD livers utilized in patients with model for end-stage liver disease (MELD) < or =30 or those not on organ-perfusion support, as graft survival was significantly lower compared to DBD patients. However, DCD and DBD subjects transplanted with MELD >30 or on organ-perfusion support had similar graft survival, suggesting a potentially greater benefit of DCD livers in critically ill patients.
Currently, patients awaiting deceased-donor liver transplantation are prioritized by medical urgency. Specifically, wait-listed chronic liver failure patients are sequenced in decreasing order of Model for End-stage Liver Disease (MELD) score. To maximize lifetime gained through liver transplantation, posttransplant survival should be considered in prioritizing liver waiting list candidates. We evaluate a survival benefit based system for allocating deceased-donor livers to chronic liver failure patients. Under the proposed system, at the time of offer, the transplant survival benefit score would be computed for each patient active on the waiting list. The proposed score is based on the difference in 5-year mean lifetime (with vs. without a liver transplant) and accounts for patient and donor characteristics. The rank correlation between benefit score and MELD score is 0.67. There is great overlap in the distribution of benefit scores across MELD categories, since waiting list mortality is significantly affected by several factors. Simulation results indicate that over 2000 life-years would be saved per year if benefit-based allocation was implemented. The shortage of donor livers increases the need to maximize the life-saving capacity of procured livers. Allocation of deceased-donor livers to chronic liver failure patients would be improved by prioritizing patients by transplant survival benefit.
Single-center studies have reported that liver allograft survival is not affected by preservation in histidine-tryptophan-ketoglutarate (HTK) versus University of Wisconsin (UW) solution. We analyzed the UNOS database of liver transplants performed from July, 2004, through February, 2008, to determine if preservation with HTK (n = 4755) versus UW (n = 12 673) impacted graft survival. HTK preservation of allografts increased from 16.8% in 2004 to 26.9% in 2008; this was particularly striking among donor after cardiac death (DCD) allografts, rising from 20.7% in 2004 to 40.9% in 2008. After adjusting for donor, recipient and graft factors that affect graft survival, HTK preservation was associated with an increased risk of graft loss (HR 1.14, p = 0.002), especially with DCD allografts (HR 1.44, P = 0.025) and those with cold ischemia time over 8 h (HR 1.16, P = 0.009). Furthermore, HTK preservation was associated with a 1.2-fold higher odds of early (< 30 days) graft loss as compared to UW preservation (OR 1.20, p = 0.012), with a more pronounced effect on allografts with cold ischemia time over 8 h (OR 1.31, p = 0.007), DCD allografts (OR 1.63, p = 0.09) and donors over 70 years (OR 1.67, p = 0.081). These results suggest that the increasing use of HTK for abdominal organ preservation should be reexamined.
Liver transplantation is the treatment of choice for many patients with acute and chronic liver failure, but its application is limited by a shortage of donor organs. Donor organ shortage is the principal cause of increasing waiting lists, and a number of patients die while awaiting transplantation. Non-heart-beating donor (NHBD) livers are a potential means of expanding the donor pool. This is not a new concept. Prior to the recognition of brainstem death, organs were retrieved from deceased donors only after cardiac arrest. Given the preservation techniques available at that time, this restricted the use of extrarenal organs for transplantation. In conclusion, after establishment of brain death criteria, deceased donor organs were almost exclusively from heart-beating donors (HBDs). To increase organ availability, there is now a resurgence of interest in NHBD liver transplantation. This review explores the basis for this and considers some of the published results.
Increasing donor hospital cooperation with donation after cardiac death (DCD) requires the organ procurement organization (OPO) to use current withdrawal of life support (WLS) protocols. Hospital ICU nurses/physicians are comfortable performing the emotionally draining procedure of WLS in the ICU while OPOs are reluctant to accept these donors due to increased warm ischemia (WI). In our area, several hospitals will only allow WLS to occur in the ICU. This study compares liver outcomes from DCD donors where death occurred in the ICU (DCDICU) vs the OR (DCDOR).
From March 2003 to June 2004, 34 DCD donors were recovered by our OPO. WLS occurred in the ICU for 26 donors (76%) and in the OR for 8 donors (24%). Thirteen of 26 DCDICU and 5 of 8 DCDOR livers were transplanted. Donor demographics, warm ischemic time, cold ischemic time, distance shipped, and recipient functions were analyzed.
Eighteen livers were transplanted both locally and at distant transplant centers. Results are outlined in the .
Although DCDICU donors averaged approximately 4 minutes longer WI than DCDOR donors, short-term results for both groups were equivalent. These findings support using DCDICU livers. DCDICU donors have the potential to significantly improve donor hospital cooperation.
Transplant physicians and candidates have become increasingly aware that donor characteristics significantly impact liver transplantation outcomes. Although the qualitative effect of individual donor variables are understood, the quantitative risk associated with combinations of characteristics are unclear. Using national data from 1998 to 2002, we developed a quantitative donor risk index. Cox regression models identified seven donor characteristics that independently predicted significantly increased risk of graft failure. Donor age over 40 years (and particularly over 60 years), donation after cardiac death (DCD), and split/partial grafts were strongly associated with graft failure, while African-American race, less height, cerebrovascular accident and 'other' causes of brain death were more modestly but still significantly associated with graft failure. Grafts with an increased donor risk index have been preferentially transplanted into older candidates (>50 years of age) with moderate disease severity (nonstatus 1 with lower model for end-stage liver disease (MELD) scores) and without hepatitis C. Quantitative assessment of the risk of donor liver graft failure using a donor risk index is useful to inform the process of organ acceptance.
The shortage of deceased donor kidneys and livers for transplantation has prompted the use of organs from donors deceased after cardiac death (DCD). We used the UNOS database to examine patient and graft survival following transplantation of DCD organs compared to those following grafts from donors deceased after brain death (DBD; for livers, grafts from donors < 60 years old were labeled '< 60 yrs'). Of 44035 deceased donor kidney transplant recipients, 1177 (3%) received a DCD kidney. There was no difference in patient or graft survival at 5 years (DCD vs. DBD: 81.3% vs. 80.8% and 66.9% vs. 66.5%; p = 0.70 and p = 0.52 respectively). Of 24688-deceased donor liver transplant recipients, 345 (1.4%) were from DCD donors and 20289 (82%) were from '< 60 yrs' DBD donors. Three-year patient and graft survival were inferior in the DCD group (DCD vs. '< 60 yrs' DBD: 77% vs. 80% and 65% vs. 75%; p = 0.016 and p < 0.0001 respectively) but were comparable to current alternatives, '>/= 60 yrs' DBD livers (donor age >/= 60) and split livers. DCD livers are a reasonable option when death is imminent. Our study demonstrates good outcomes using DCD kidneys and livers and encourages their use.
We describe the first cases of reuse of auxiliary liver grafts for orthotopic transplantation in chronic liver disease. A reduced liver graft (segments 2, 3, half of 4) was first transplanted auxiliary for acute liver failure using a new technique. After regeneration of both native liver and graft, the auxiliary graft was removed and immunosuppression discontinued in the first recipients. After informed consent of donors and recipients, both auxiliary grafts were then orthotopically transplanted into second recipients. Both grafts function normally. Reuse of auxiliary grafts may help to reduce the shortage or liver grafts available for transplantation.
Unlabelled:
Retransplantation (RT) in Hepatitis C (HCV) patients remains controversial.
Aims:
To study trends in RT and evaluate the impact of HCV status in the context of a comprehensive recipient and donor risk assessment. The UNOS database between 1994 and October 2005 was utilized to analyze 46 982 LT and RT. Graft and patient survival along with patient and donor characteristics were compared for 2283 RT performed in HCV and non-HCV patients during 1994-1997, 1998-2001 and 2002-October 2005. Overall HCV prevalence at RT increased from 36% in the initial period to 40.6% after 2002. In our study group, 1-year patient and graft survival post-RT improved over the same time intervals from 65.0% to 70.7% and 54.87% to 65.8%, respectively. HCV was only associated with decreased patient and graft survival with a retransplant (LT-RT) interval (RI) >90 days. Independent predictors of mortality for RT with RI >90 days were patient age, MELD score >25, RI <1 year, warm ischemia time > or =75 min and donor age > or =60 (significant for HCV patients only). Outcomes of RT are improving, but can be optimized by weighing recipient factors, anticipation of operative factors and donor selection.
Background
Donation after cardiac death is a method by which severely neurologically injured patients not fulfilling brain-death criteria can donate organs.
Objective
To develop an evaluation tool that can be used to predict if a patient is a suitable candidate for donation after cardiac death.
Methods
The University of Wisconsin Donation After Cardiac Death Evaluation Tool assigns numeric values to observable clinical parameters to yield an overall predictive score of suitability for donation after cardiac death. This evaluation tool is typically utilized in a critical care unit to evaluate patients with a severe neurological injury, who do not meet brain-death criteria, and for whom the physician and family have chosen to terminally withdraw life support. Each patient is disconnected from a ventilator and observed for up to 10 minutes. Observations are then scored to yield a prediction of suitability for donation after cardiac death.
Results
Using the University of Wisconsin Donation After Cardiac Death Evaluation Tool, we were able to predict suitability for donation after cardiac death 83.7% of the time, within a 60-minute period and 74.4% of the time within a 120-minute period. The actual results using the tool were higher when clinical observations were included in the donation after cardiac death evaluation—an overall accuracy of 88.4%.
Organ shortage for liver transplantation continues to be a major problem. Non heart beating donors (NHBD) are gaining increasing importance as a potential source of transplantable organs for clinical use, mainly in kidney transplantation. Up to now, the experience in liver transplantation with this type of donors has been limited and has only been considered in donors in whom cardiac arrest (CA) has occured at a known given time. This is due to the high risk of primary non-function and late complications related to intrahepatic biliary lesions when warm ischemia time (WIT) is not controlled. The method of retrieval of these organs should offer the possibility to stop liver injury, revert hisologic lesions appeared after WIT, and to assess the quality of the potential donor liver. Based on the experience of kidney transplantation, total body cooling achieved by extracorporal cardiopulmonary bypass seems to be the best method. Moreover it allows the inclusion of a time for tissue oxygenation at 37 degreesC (Normothermic Recirculation, NR) prior to body cooling which has been shown to improve graft viability, and also allows a time to measure organ quality before transplantation. In our experience, we demonstrated that liver transplantation from NHBD is feasible; NR has beneficial effect on liver viability improving endothelial cell damage, hepatocyte energy charge and histological changes at 5 days. We also showed that time of cardiac arrest is determinant of graft viability; even if hepatocellular function is preserved after 40 minutes of CA using NR, irreversible intrahepatic biliary lesions are always present and burden long-term survival. Moreover. bypass pump and blood flows an directly related to WIT and the achievement of better pump flows may predict survival during NR. In animals with 40 minutes of CA, we also reported the possibility to manipulate the potential graft during NR with L-Arginine, Glycine and S-Adenosyl-Methyonine, which minimize endothelial and hepatocellular damage as well as lesions at 5 days. Further research needs to be done in order to confirm our experimental data.
The use of donation after cardiac death (DCD) donors may provide a valuable source of organs for liver transplantation. Concerns regarding primary nonfunction (PNF) and intrahepatic biliary stricture (IHBSs) have limited the enthusiasm for their use. A retrospective analysis of 1436 consecutive deceased donor liver transplants performed between December 1998 and October 2006 was conducted. These included 108 DCD liver transplants, which were compared to 1328 transplants performed with organs from donors meeting the criteria for donation after brain death (DBD). The median follow-up was 48 months. The 1-, 3-, and 5-year patient survival and graft survival for DCD donors were 91.5%, 88.1%, and 88.1% and 79.3%, 74.5%, and 71.0%, respectively. The 1-, 3-, and 5-year patient survival and graft survival for DBD donors were 87.3%, 81.1%, and 77.2% and 81.6%, 74.7%, and 69.1%, respectively. Patient survival and graft survival were not significantly different between DCD donors less than 60 years old, DCD donors greater than 60 years old, and DBD donors. Causes of graft loss included IHBSs (n = 9), PNF (n = 4), recurrent hepatitis C virus (n = 4), hepatic artery thrombosis (n = 1), rejection (n = 2), and patient death (n = 13). Contrary to previously published data, excellent long-term patient survival and graft survival can be obtained with DCD allografts, and in our experience, they are equivalent to those obtained from DBD allografts.
Grafts from donation after cardiac death (DCD) donors are used to increase the number of organs available for liver transplantation. There is concern that warm ischemia may impair graft function. We compared our DCD recipients with a case-matched group of donation after brain death (DBD) recipients. Between January 2002 and April 2008, 39 DCD grafts were transplanted. These were matched with 39 DBD recipients on the basis of identified variables that had a significant impact on mortality. These were used to individually match DCD and DBD patients with similar predictive mortality. We compared patient/graft survival, primary non-function (PNF), and rates of complications. Of all liver transplants, 6.1% were DCD grafts. PNF occurred twice in the DCD group. The incidence of nonanastomotic biliary strictures (NABS; 20.5% versus 0%, P = 0.005) and hepatic artery stenosis (HAS; 12.8% versus 0%, P = 0.027) in the DCD group was higher. One-year (79.5% versus 97.4%, P = 0.029) and 3-year (63.6% versus 97.4%, P = 0.001) graft survival was lower in the DCD group. Three-year patient survival was also lower (68.2% versus 100%, P < 0.0001). Our study is the first to use case-matched patients and compare groups with similar predictive mortality. There was a higher incidence of NABS and HAS in the DCD group. NABS were likely a result of warm ischemia. HAS may have been due to ischemia or arterial injury during retrieval. The DCD group had significantly poorer outcomes, but DCD grafts remain a valuable resource. With careful donor/recipient selection, minimization of ischemia, and good postoperative care, acceptable results can be achieved.
Utilization, outcomes, and retransplantation (ReTx) of liver allografts obtained by donation after cardiac death (DCD) are examined to identify mechanisms to optimize donation.
DCD for liver transplantation (LTX) has immediate potential to expand the donor pool but application is limited.
Retrospective analysis of the Scientific Registry of Transplant Recipients (SRTR) from January 2002 to April 2007 identified 855 DCD and 21,089 donation after brain death (DBD) adult, initial, whole-organ, liver-only LTX. Donor, recipient, and transplant characteristics were compared. Outcome measures were listing for ReTx within 1 year and graft survival determined as death or ReTx.
DCD donors were younger (P < 0.001), with fewer African American and non-white race (P < 0.001), and fewer deaths secondary to stroke (P < 0.001). DCD recipients were older (P < 0.001), with lower Model for End-Stage Liver Disease (MELD) scores (P < 0.001), and less likely in intensive care (P = 0.02) or high-urgency status (P < 0.001). DCD allografts were more frequently imported from another allocation region (12% vs. 7%; P < 0.001). Cox regression analysis of time to DCD graft failure demonstrates higher DCD graft failure within the first 180 days (20.5% DCD vs. 11.5% DBD; P < 0.001) with convergence thereafter. DCD listing for ReTx and graft failure progressed continuously over 180 days versus 20 days in DBD. At ReTx, DCD recipients waited longer and received higher risk allografts (P = 0.039) more often from another region. More DCD recipients remain waiting for ReTx with fewer removed for death, clinical deterioration, or improvement.
DCD utilization is impeded by early outcomes and a temporally different failure pattern that limits access to ReTx. Allocation policy that recognizes these limitations and increases access to ReTx is necessary for expansion of this donor population.
Organ shortage for liver transplantation continues to be a major problem. Non heart beating donors (NHBD) are gaining increasing importance as a potential source of transplantable organs for clinical use, mainly in kidney transplantation. Up to now, the experience in liver transplantation with this type of donors has been limited and has only been considered in donors in whom cardiac arrest (CA) has occurred at a known given time. This is due to the high risk of primary non-function and late complications related to intrahepatic biliary lesions when warm ischemia time (WIT) is not controlled. The method of retrieval of these organs should offer the possibility to stop liver injury, revert histologic lesions appeared after WIT, and to assess the quality of the potential donor liver. Based on the experience of kidney transplantation, total body cooling achieved by extracorporal cardiopulmonary bypass seems to be the best method. Moreover it allows the inclusion of a time for tissue oxygenation at 37 degrees C (Normothermic Recirculation, NR) prior to body cooling which has been shown to improve graft viability, and also allows a time to measure organ quality before transplantation. In our experience, we demonstrated that liver transplantation from NHBD is feasible; NR has beneficial effect on liver viability improving endothelial cell damage, hepatocyte energy charge and histological changes at 5 days. We also showed that time of cardiac arrest is determinant of graft viability; even if hepatocellular function is preserved after 40 minutes of CA using NR, irreversible intrahepatic biliary lesions are always present and burden long-term survival. Moreover, bypass pump and blood flows are directly related to WIT and the achievement of better pump flows may predict survival during NR. In animals with 40 minutes of CA, we also reported the possibility to manipulate the potential graft during NR with L-Arginine, Glycine and S-Adenosyl-Methyonine, which minimize endothelial and hepatocellular damage as well as lesions at 5 days. Further research needs to be done in order to confirm our experimental data.
The limits of organ donation from heart-beating (HB) donors reached a plateau illustrated by the number of postmortem kidneys for transplantation. Programs such as the European Donor Hospital Education Program (EDHEP) and Donor Action have helped to stop a further decrease in the number instead of an expected increase. For kidneys, heart, liver, and lungs one must also explore the use of marginal donors as a possible additional source. Examples are donors with a horseshoe kidney, those at both ends of the age spectrum, and those with medical contraindication such as diabetes. We have enlarged our kidney donor pool considerably with non-heart-beating(NHB) donors. Because we preserve these kidneys in a preservation machine, we are able to perform viability testing. With glutathione S-transferase (GST) as a measure of tubular damage, we now decide whether to transplant based on GST values. For other organs, NHB donation does not seem to be an option other than for the liver when the warm ischemia time is short.
Hepatic allografts from non-heart-beating donors (NHBD) have been cited as a means to expand the supply of donor livers. Concern exists that donor warm ischemic time in addition to subsequent cold ischemia-reperfusion injury may result in damage to sensitive cell populations within the liver. Because the biliary epithelium is sensitive to ischemia-reperfusion injury, the authors surmised that an increased incidence of biliary complications might occur among recipients of an NHBD allograft.
This study was a retrospective evaluation of NHBD recipients compared to a group of heart-beating donor (HBD) recipients from a single institution.
Fifteen patients received a hepatic allograft from a controlled NHBD donor. NHBD and HBD (n=221) graft survival did not differ at 1 (71.8% vs. 85.4%, P=0.23) or 3 years (71.8% vs. 73.9%, P=0.68). Patient survival at 1 (79% vs. 90.9%, P=0.16) and 3 years (79.0% vs. 77.7%, P=0.8) was also similar. Major biliary complications occurred in five (33.3%) NHBD recipients; 66.6% of the NHBD biliary complications consisted of intrahepatic strictures versus 19.2% among HBD recipients (P<0.01). Major biliary complications in the NHBD recipients resulted in multiple interventional procedures, retransplantation, and death.
Donor warm ischemic time may predispose hepatic allografts to an increased incidence of ischemic type strictures. Although graft and patient survival was similar to a cohort of HBD recipients, caution is urged with the use of these organs.
The shortage of organs has led centers to expand their criteria for the acceptance of marginal donors. The combination of multiple marginal factors seems to be additive on graft injury. In this review, the utility of various marginal donors in patients requiring liver transplantation will be described, including older donors, steatotic livers, non-heart-beating donors, donors with viral hepatitis, and donors with malignancies. The pathophysiology of the marginal donor will be discussed, along with strategies for minimizing the ischemia reperfusion injury experienced by these organs. Finally, new strategies for improving the function of the marginal/expanded donor liver will be reviewed.
The demand for liver transplantation has increasingly exceeded the supply of cadaver donor organs. Non-heart-beating donors (NHBDs) may be an alternative to increase the cadaver donor pool.
The outcome of 20 liver transplants from Maastricht category 2 NHBDs is compared with 40 liver transplants from heart-beating donors (HBDs). After unsuccessful cardiopulmonary resuscitation (CPR), cardiopulmonary support (CPS) with simultaneous application of chest and abdominal compression (n=6), and cardiopulmonary bypass (CPB; n=14), which was hypothermic (n=7) or normothermic (n=7), were used to preserve the organs from NHBDs. Factors that may influence the outcome of livers from Maastricht category 2 NHBDs were also investigated.
With a minimum follow-up of 2 years, actuarial patient and graft survivals with livers from Maastricht category 2 NHBDs were 80% and 55%, respectively. Transplantation of organs from these donors was associated with a significantly higher incidence of primary nonfunction, biliary complications, and more severe initial liver dysfunction compared with livers from HBDs. Graft survival was 83% in livers from NHBDs preserved with CPS and 42% in those maintained with CPB. No graft failed if the duration of warm ischemia did not exceed 130 min with CPR or CPS, and if the period of CPB did not surpass 150 min when this method was used after CPR, regardless if it was hypothermic or normothermic.
Livers from Maastricht type 2 NHBDs may be used for transplantation if the period of warm ischemia during CPR or CPS does not exceed 130 min. Hypothermic or normothermic CPB after CPR preserves liver viability for an additional 150 min.
Donation after cardiac death is a method by which severely neurologically injured patients not fulfilling brain-death criteria can donate organs.
To develop an evaluation tool that can be used to predict if a patient is a suitable candidate for donation after cardiac death.
The University of Wisconsin Donation After Cardiac Death Evaluation Tool assigns numeric values to observable clinical parameters to yield an overall predictive score of suitability for donation after cardiac death. This evaluation tool is typically utilized in a critical care unit to evaluate patients with a severe neurological injury, who do not meet brain-death criteria, and for whom the physician and family have chosen to terminally withdraw life support. Each patient is disconnected from a ventilator and observed for up to 10 minutes. Observations are then scored to yield a prediction of suitability for donation after cardiac death.
Using the University of Wisconsin Donation After Cardiac Death Evaluation Tool, we were able to predict suitability for donation after cardiac death 83.7% of the time, within a 60-minute period and 74.4% of the time within a 120-minute period. The actual results using the tool were higher when clinical observations were included in the donation after cardiac death evaluation--an overall accuracy of 88.4%.
The objective of this analysis was to compare the results of transplantation of livers, pancreases, kidneys, and lungs from donation after cardiac death (DCD) donors to organs transplanted from donation after brain death (DBD) donors.
From January 1984 through July 2000, outcomes of 382 DCD kidneys were compared to 1,089 kidneys (SPK) transplants and 36 liver transplants from DCD donors were compared to 455 SPK and 510 liver transplants from DBD donors. Likewise, 31 simultaneous pancreas-kidneys transplants from DBD donors.
The rate of delayed graft function (DGF) was higher in kidneys transplanted from DCD donors (27.5% versus 21.3%, p=0.01). Likewise, discharge creatinines were higher in recipients of DCD kidneys (1.9 mg/dL versus 1.7 mg/dL, p=0.001). There was no difference in 10-year graft survival between DCD and DBD recipients (45.0% versus 48.0%, p=0.054). No difference in 5-year pancreatic and renal allograft survival was seen after SPK from DCD or DBD donors. After liver transplantation, biliary strictures were higher in recipients of DCD livers (13.9% versus 8.0%, p=0.03). Likewise, 3-year patient and graft survivals were lower for recipients of DCD livers (65.8% versus 84.9%, p=0.01; and 58.6% versus 76.9%, p=0.006).
This large experience with transplantation from DCD donors demonstrates that similar patient and graft survivals can be expected when compared to recipients of organs from DBD donors.
This study examines donation after cardiac death (DCD) practices and outcomes in liver transplantation.
Livers procured from DCD donors have recently been used to increase the number of deceased donors and bridge the gap between limited organ supply and the pool of waiting list candidates. Comprehensive evaluation of this practice and its outcomes has not been previously reported.
A national cohort of all DCD and donation after brain-death (DBD) liver transplants between January 1, 2000 and December 31, 2004 was identified in the Scientific Registry of Transplant Recipients. Time to graft failure (including death) was modeled by Cox regression, adjusted for relevant donor and recipient characteristics.
DCD livers were used for 472 (2%) of 24,070 transplants. Annual DCD liver activity increased from 39 in 2000 to 176 in 2004. The adjusted relative risk of DCD graft failure was 85% higher than for DBD grafts (relative risk, 1.85; 95% confidence interval, 1.51-2.26; P < 0.001), corresponding to 3-month, 1-year, and 3-year graft survival rates of 83.0%, 70.1%, and 60.5%, respectively (vs. 89.2%, 83.0%, and 75.0% for DBD recipients). There was no significant association between transplant program DCD liver transplant volume and graft outcome.
The annual number of DCD livers used for transplant has increased rapidly. However, DCD livers are associated with a significantly increased risk of graft failure unrelated to modifiable donor or recipient factors. Appropriate recipients for DCD livers have not been fully characterized and recipient informed consent should be obtained before use of these organs.
Donation after cardiac death (DCD) is recognized as an important source of allografts to bridge the growing disequilibrium between the number of donors and recipients. Current transplant experience with DCD organs has focused on the adult recipient population, however little is known about the pediatric recipient experience. While there is increasing acceptance of these grafts in adults, transplant centers appear reluctant to use these grafts in the pediatric population.
We reviewed the United Network for Organ Sharing database from 1995-2005 to determine the national experience with pediatric recipients of DCD organs.
Among 4026 renal transplants performed in children 18 years and younger, 26 (0.6%) received a renal allograft from a DCD donor. Ten (38.5%) received kidney allografts from pediatric donors (age < or = 18) and 16 (61.5%) from adult donors (age > 18 years). Graft survival at one and five years was 82.5%, 74.3% for kidneys from DCD donors compared to 89.6%, 64.8% from brain dead donors (DBD) (P = 0.7). Among 4991 liver transplants, 19 (0.4%) were from DCD donors. Sixteen patients (84.2%) received livers from pediatric donors and three (15.8%) from adult donors. Graft survival at one and five years was 89.2%, 79.3% for livers from DCD, compared to 75.6%, 65.8% for DBD (P = 0.3).
The use of DCD donors in the pediatric population is very limited; however graft survival is comparable to DBD grafts. Although pediatric centers may have been reluctant to utilize this donor source, this limited experience demonstrates that the select use of DCD organs can produce acceptable and durable graft survival in the pediatric population.
Liver transplantation from donation after cardiac death (DCD) donors is an increasingly common approach for expansion of the donor organ supply. However, transplantation with DCD livers results in inferior graft survival. In this study, we examined donor and recipient characteristics that are associated with poor allograft outcomes and present a set of criteria that permit allograft survival that is comparable to that of donation after brain death (DBD) grafts in both low- and high-risk recipients.
The United Network for Organ Sharing/Organ Procurement and Transplantation Network Liver Transplantation Registry between January 1996 and March 2006 was investigated. Adult DCD liver transplants (n = 874) were included.
A DCD risk index was developed using the statistically significant factors from a multivariate Cox model: history of previous transplantation, life support status at transplantation, donor age, donor warm ischemia time (DWIT), and cold ischemia time (CIT). Favorable DCD donor criteria were donor age < or =45 years, DWIT < or =15 min, and CIT < or =10 hr. Four risk groups were developed based upon index scores that showed different graft survival. Graft survival of the favorable DCD group (84.9% at 1 year, 75.2% at 3 years, and 69.4% at 5 years) was comparable to that for DBD liver transplantation irrespective of recipient condition. Increasing donor age was more highly predictive of poor outcomes in DCD compared to DBD, especially in recipients in poor preoperative condition.
DCD livers from young donors with short DWIT and CIT should be given greater consideration in order to expand the number of available donor organs.
Liver transplantation (LT) from controlled donation after cardiac death (DCD) donors has increased steadily during the past decade because of the donor shortage in the United States. Although early reports of LT from DCD donors provided evidence for acceptable outcomes, long-term graft and patient survival rates from these procedures have been reviewed only recently.
From February 1990 to June 2006, 1209 LTs were performed from donation after brain death (DBD) donors, and 24 were performed from DCD donors at our institution. Detailed review of donor and recipient characteristics, and survival rates were evaluated in the two groups.
One- and 3-year patient survival was similar in both groups, (DCD 86.8%, 81.7% vs. DBD 84.0%, 76.0%, respectively; P=0.713). Graft survival appeared inferior in the DCD group compared with the DBD group at 1 year (69.1% vs. 78.7%) and 3 years (58.6% vs. 70.2%), but there was no statistical difference (P=0.082). There were no significant differences in hepatic artery thrombosis, portal vein thrombosis, primary nonfunction, and biliary stricture between the two groups. All cases with biliary stricture in DCD group finally led to graft loss, and all survived with retransplantation.
The outcome of LT from DCD donors remains acceptable in our institution. Although biliary complication rate was similar in two groups, the consequence of this complication in DCD was more severe and often led to graft loss. Close observation of biliary complications after LT from DCD donors would be beneficial.
Biliary complications after liver transplantation (LT) using organs retrieved from donors after cardiac death are not well characterized. The aim of this study was to evaluate the severity of biliary complications and outcomes after donation after cardiac death liver transplantation (DCD-LT). A retrospective evaluation of 20 DCD-LTs from 1997-2006 was performed. The recipient age was 53+/-8.7, and the donor age was 35+/-11 years. The warm ischemia time, cold ischemia time, peak alanine aminotransferase level, and peak aspartate aminotransferase level were 33+/-12 minutes, 8.7+/-2.7 hours, 1757+/-1477 U/L, and 4020+/-3693 U/L, respectively. The bilirubin and alkaline phosphatase levels at hospital discharge after LT were 3.2+/-5.4 mg/dL and 248+/-200 U/L, respectively. During a median follow-up of 7.5 months (range: 1-73), 5 patients (25%; 1 death after re-LT) died (3 from sepsis, 1 from recurrent hepatocellular carcinoma at 4 months, and 1 from a cardiac event at 46 months), and additionally, 4 patients (20%) required re-LT (1 because of hepatic artery thrombosis, 1 because of primary graft nonfunction, and 2 because of biliary strictures). Twelve (60%) developed biliary complications, and of these, 11 (55%) had serious biliary complications. The biliary complications were as follows: a major bile leak for 2 patients (10%; both eventually underwent retransplantation), anastomotic strictures for 5 patients (25%), hilar strictures for 7 patients (35%), extrahepatic donor duct strictures for 9 patients (45%), intrahepatic strictures for 10 patients (50%), stones for 1 patients (5%), casts for 7 patients (35%), and debris for 2 patients (10%). More than 1 biliary complication was seen in most patients, and these were unpredictable and required multiple diagnostic or therapeutic procedures. Serious biliary complications are common after DCD-LT, and research should focus on identifying donor and recipient factors that predict and prevent serious biliary complications.
1. This is a retrospective study using the UNOS database to examine the effects of various recipient, donor and transplant factors on 10-year liver graft survivals. A total of 68,776 adult liver transplants were reported to OPTN/UNOS from September 1987 to July 2006. Recipient, donor and transplant characteristics were compared using the paired t test for continuous variables. The chi-square tests were used to compare categorical variables. We calculated actual liver graft survival rates using the Kaplan-Meier methods. For statistical comparisons of survival curves, we used log-rank analysis. 2. The number of recipients who were older than 65 years of age has been steadily increasing each year. Since 1998, more than 10% of all recipients were over 65 years old, and in 2003 it reached 15.3%. The 1-, 5- and 10-year graft survival rates of liver transplant recipients who were younger than 65 years were 82.1%, 67.8% and 52.6%, respectively; for recipients who were 65 years or older they were 77.5%, 59.7% and 41.2%, respectively. 3. The impact of recipient, donor and transplant factors on liver graft survivals changed over time after liver transplantation. Recipient age, sex, having diabetes or angina and being positive against HCV antibody had both short- and long- term effects on transplant grafts. Pre-transplant dialysis and cold ischemia time had only short-term effects. 4. Our results showed that the transplants from older donors, DCD donors, HCV antibody-positive donors and diabetic donors had poorer graft survival than the transplants from other types of donors. 5. When the grafts which failed within one year were excluded from analyses, recipients whose serum total bilirubin at transplantation was higher than 7 mg/dL or recipients who were on mechanical ventilation at transplantation had better liver graft survival compared to other recipients. The better prognosis among recipients with higher total bilirubin or recipients on mechanical ventilation is partially explained by younger recipient age in these recipient groups. 6. The present allocation policy, the MELD-based deceased donor liver allocation system, mainly assigns a donor to a recipient depending on recipient pre-transplant medical status. However, to optimize the use of limited organs, not only pre-transplant recipient status but also expected liver graft outcome based donor assignment to recipients should be incorporated. 7. In conclusion, our study on ten-year liver graft survival showed that impacts of recipient, donor and transplant factors on liver graft survivals changed over time after liver transplantation.
The use of donation after cardiac death (DCD) donor hepatic allografts is becoming more widespread; however, there have been published reports of increased graft failure from specific complications associated with this type of allograft. The complication of ischemic cholangiopathy (IC) has been reported to occur more frequently after the use of DCD hepatic allografts. We report the results of 52 liver transplants from DCD donors and the factors that influenced the development of IC. We conducted a retrospective review of all DCD and donation after brain death (DBD) donor liver recipients from September 2003 through December 2006 at a single institution. Survival and complication rates were compared between the 2 groups. The Cox proportional hazards model was then used to identify recipient and donor factors that predict the development of IC in the DCD group. There was no difference in 1-year patient or graft survival rates between the 2 groups. There was no incidence of primary nonfunction from the DCD allografts. Hepatic artery complications and anastomotic bile duct complications were comparable in the 2 groups. There was, however, an increased risk for the development of IC in the DCD group (13.7% versus 1%, P = 0.001). Donor weight >100 kg and total ischemia times > or =9 hours, in donors older than 50 years of age, predicted the development of IC in the DCD group. In conclusion, there is a higher incidence of IC in recipients receiving DCD donor livers; however, patient and graft outcomes with DCD donors remain comparable to those with DBD donors. Careful donor selection may improve utilization of these grafts.
Compared with standard donors, kidneys recovered from donors after cardiac death (DCD) exhibit higher rates of delayed graft function (DGF), and DCD livers demonstrate higher rates of biliary ischemia, graft loss, and worse patient survival. Current practice limits the use of these organs based on time from donor extubation to asystole, but data to support this is incomplete. We hypothesized that donor postextubation parameters, including duration and severity of hemodynamic instability or hypoxia might be a better predictor of subsequent graft function.
We performed a retrospective examination of the New England Organ Bank DCD database, concentrating on donor factors including vital signs after withdrawal of support.
Prolonged, severe hypotension in the postextubation period was a better predictor of subsequent organ function that time from extubation to asystole. For DCD kidneys, this manifested as a trend toward increased DGF. For DCD livers, this manifested as increased rates of poor outcomes. Maximizing the predictive value of this test in the liver cohort suggested that greater than 15 min between the time when the donor systolic blood pressure drops below 50 mm Hg and flush correlates with increased rates of diffuse biliary ischemia, graft loss, or death. Donor age also correlated with worse outcome.
Time between profound instability and cold perfusion is a better predictor of outcome than time from extubation to asystole. If validated, this information could be used to predict DGF after DCD renal transplant and improve outcomes after DCD liver transplant.
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