Undine Samuel

Longterm results of liver transplantation from donation after circulatory death

Donation after circulatory death (DCD) liver transplantation (LT) may imply a risk for decreased graft survival, caused by posttransplantation complications such as primary nonfunction or ischemic‐type biliary lesions. However, similar survival rates for DCD and donation after brain death (DBD) LT have been reported. The objective of this study is to determine the longterm outcome of DCD LT in the Eurotransplant region corrected for the Eurotransplant donor risk index (ET‐DRI). Transplants performed in Belgium and the Netherlands (January 1, 2003 to December 31, 2007) in adult recipients were included. Graft failure was defined as either the date of recipient death or retransplantation whichever occurred first (death‐uncensored graft survival). Mean follow‐up was 7.2 years. In total, 126 DCD and 1264 DBD LTs were performed. Kaplan‐Meier survival analyses showed different graft survival for DBD and DCD at 1 year (77.7% versus 74.8%, respectively; P = 0.71), 5 years (65.6% versus 54.4%, respectively; P = 0.02), and 10 years (47.3% versus 44.2%, respectively; P = 0.55; log‐rank P = 0.038). Although there was an overall significant difference, the survival curves almost reach each other after 10 years, which is most likely caused by other risk factors being less in DCD livers. Patient survival was not significantly different (P = 0.59). Multivariate Cox regression analysis showed a hazard ratio of 1.7 (P < 0.001) for DCD (corrected for ET‐DRI and recipient factors). First warm ischemia time (WIT), which is the time from the end of circulation until aortic cold perfusion, over 25 minutes was associated with a lower graft survival in univariate analysis of all DCD transplants (P = 0.002). In conclusion, DCD LT has an increased risk for diminished graft survival compared to DBD. There was no significant difference in patient survival. DCD allografts with a first WIT > 25 minutes have an increased risk for a decrease in graft survival. Liver Transplantation 22 1107–1114 2016 AASLD

Adult Liver Allocation in Eurotransplant.

Abstract Liver allocation in Eurotransplant is complex because allocation rules need to follow not only the guidelines of the European Commission but also the specific regulations of each of the 7 Eurotransplant countries with active liver transplant programs. Thirty-eight liver transplant centers served a population of about 135 million in 2015. Around 1600 deceased donor livers are transplanted annually. The number of deceased organ donors remains stable but donor age is increasing. Nevertheless, liver utilization rates are unchanged at around 80%. Donation after circulatory determination of death (DCD) increased fourfold in the past decade. In Belgium and the Netherlands, DCDs were responsible for 30% of deceased donor liver transplant activity in 2015; Austria only occasionally transplants a DCD liver; other Eurotransplant countries do not have active DCD programs. The most frequent indications for liver transplantation are alcoholic liver disease, hepatocellular carcinoma, and viral hepatitis. Livers are allocated first internationally to high urgency status patients or those with an approved combined organ status (for a liver in combination with heart, lung, intestine, or pancreas) and then on a national basis where allocation is recipient-driven or center-driven, depending on country-specific rules. Median waiting time for an elective liver transplant was 4,4 months in 2015; high urgency status patients waited a median of 2 days for a suitable liver. Mortality on the waiting list was 18% in 2015, 4% of patients were delisted because they became unfit for transplantation. One-year and 5-year risk unadjusted adult patient survival after transplantation is 80% and 65%, respectively.

Combined effect of donor and recipient risk on outcome after liver transplantation: Research of the Eurotransplant database

Recently the Eurotransplant donor risk index (ET‐DRI) was published, a model based on data from the Eurotransplant database that can be used for risk indication of liver donors within the Eurotransplant region. Because outcome after liver transplantation (LT) depends both on donor and recipient risk factors, a combined donor‐recipient model (DRM) would give a more complete picture of the overall risk involved. All liver transplants in adult recipients from January 1, 2008 to December 31, 2010 in the Eurotransplant region were included. Risk factors in donors and recipients for failure‐free (retransplant free) survival were analyzed in univariate and multivariate analyses. A simplified recipient risk index (sRRI) was constructed using all available recipient factors. A total of 4466 liver transplants were analyzed. Median donor risk index and ET‐DRI were 1.78 and 1.91, respectively. The ET‐DRI was validated in this new cohort (P < 0.001; concordance index [c‐index], 0.59). After construction of a simplified recipient risk index of significant recipient factors, Cox regression analysis showed that the combination ET‐DRI and sRRI into a new DRM gave the highest predictive value (P < 0.001; c‐index, 0.62). The combined model of ET‐DRI and sRRI gave a significant prediction of outcome after orthotopic LT in the Eurotransplant region, better than the ET‐DRI alone. This DRM has potential in comparing data in the literature and correcting for sickness/physical condition of transplant recipients. It is a first step toward benchmarking of graft survival in the Eurotransplant region. Liver Transpl 21:1486‐1493, 2015.

Center Volume Is Associated With Outcome After Pancreas Transplantation Within the Eurotransplant Region.

Background Outcome after surgery depends on several factors, among these, the annual volume-outcome relationship. This might also be the case in a highly complex field as pancreas transplantation. No study has investigated this relationship in a European setting. Methods All consecutive pancreas transplantations from January 2008 until December 2013 were included. Donor-, recipient-, and transplant-related factors were analyzed for their association with patient and graft survivals. Centers were classified in equally sized groups as being low volume (<5 transplantations on average each year in the 5 preceding years), medium volume (5-13/year), or high volume (≥13/year). Results In the study period, 1276 pancreas transplantations were included. Unadjusted 1-year patient survival was associated with center volume and was best in high volume centers, compared with medium and low volume: 96.5%, 94% and 92.3%, respectively (P = 0.017). Pancreas donor risk index (PDRI) was highest in high volume centers: 1.38 versus 1.21 in medium and 1.25 in low volume centers (P < 0.001). Pancreas graft survival at 1 year did not differ significantly between volume categories: 86%, 83.2%, and 81.6%, respectively (P = 0.114). After multivariate Cox-regression analysis, higher PDRI (hazard ratio [HR], 1.60; P < 0.001), retransplantation (HR, 1.91; P = 0.002), and higher recipient body mass index (HR, 1.04; P = 0.024) were risk factors for pancreas graft failure. High center volume was protective for graft failure (HR, 0.70; P = 0.037) compared with low center volume. Conclusion Patient and graft survival after pancreas transplantation are superior in higher volume centers. High volume centers have good results, even though they transplant organs with the highest PDRI.

Family over rules? an ethical analysis of allowing families to overrule donation intentions

Abstract Millions of people want to donate their organs after they die for transplantation, and many of them have registered their wish to do so or told their family and friends about their decision. For most of them, however, this wish is unlikely to be fulfilled, as only a small number of deaths (1% in the United Kingdom) occur in circumstances where the opportunity to donate organs is possible. Even for those who do die in the “right” way and have recorded their wishes or live in a jurisdiction with a “presumed consent” system, donation often does not go ahead because of another issue: their families refuse to allow donation to proceed. In some jurisdictions, the rate of “family overrule” is over 10%. In this article, we provide a systematic ethical analysis of the family overrule of donation of solid organs by deceased patients, and examine arguments both in favor of and against allowing relatives to “veto” the potential donors intentions. First, we provide a brief review of the different consent systems in various European countries, and the ramifications for family overrule. Next, we describe and discuss the arguments in favor of permitting donation intentions to be overruled, and then the arguments against doing so. The “pro” arguments are: overrule minimises family distress and staff stress; families need to cooperate for donation to take place; families might have evidence regarding refusal; and failure to permit overrules could weaken trust in the donation system. The “con” arguments are: overrule violates the patients wishes; the family is too distressed and will regret the decision; overruling harms other patients; and regulations prohibit overrule. We conclude with a general discussion and recommendations for dealing with families who wish to overrule donation. Overall, overrule should only rarely be permitted.

The Impact of Anastomosis Time During Kidney Transplantation on Graft Loss: A Eurotransplant Cohort Study.

Recent studies raised the concern that warm ischemia during completion of vascular anastomoses in kidney implantation harms the transplant, but its precise impact on outcome and its interaction with other risk factors remain to be established. We investigated the relationship between anastomosis time and graft survival at 5 years after transplantation in 13 964 recipients of deceased donor solitary kidney transplants in the Eurotransplant region. Anastomosis time was independently associated with graft loss after adjusting for other risk factors (adjusted hazard ratio [HR] 1.10 for every 10‐min increase, 95% confidence interval [CI] 1.06–1.14; p < 0.0001), whereas it did not influence recipient survival (HR 1.00, 95% CI 0.97–1.02). Kidneys from donation after circulatory death (DCD) were less tolerant of prolonged anastomosis time than kidneys from donation after brain death (p = 0.02 for interaction). The additive effect of anastomosis time with donor warm ischemia time (WIT) explains this observation because DCD status was no longer associated with graft survival when adjusted for this summed WIT, and there was no interaction between DCD status and summed WIT. Time to create the vascular anastomoses in kidney transplantation is associated with inferior transplant outcome, especially in recipients of DCD kidneys.

Higher Retransplantation rate following Extended Right Split-Liver Transplantation - An analysis from the Eurotransplant Liver follow-up Registry

Split‐liver transplantation has been perceived as an important strategy to increase the supply of liver grafts by creating 2 transplants from 1 allograft. The Eurotransplant Liver Allocation System (ELAS) envisages that the extended right lobes (ERLs) after splitting (usually in the pediatric center) are almost exclusively shipped to a second center. Whether the ELAS policy impacts the graft and patient survival of extended right lobe transplantation (ERLT) in comparison to whole liver transplantation (WLT) recipients remains unclear. Data on all liver transplantations performed between 2007 and 2013 were retrieved from the Eurotransplant Liver Follow‐up Registry (n = 5351). Of these, 5013 (269 ERL, 4744 whole liver) could be included. The impact of the transplant type on patient and graft survival was evaluated using univariate and multivariate proportional hazard models adjusting for demographics of donors and recipients. Cold ischemia times were significantly prolonged for ERLTs (P < 0.001). Patient survival was not different between ERLT and WLT. In the univariate analysis, ERLT had a significantly higher risk for retransplantation (P = 0.02). For WLT, the risk for death gradually and significantly increased with laboratory Model for End‐Stage Liver Disease (MELD) scores of >20. For ERLT, this effect was seen already with laboratory MELD scores of >14. These results mandate a discussion on how to refine the splitting policy to avoid excess retransplant rates in ERL recipients and to further improve transplant outcomes of these otherwise optimal donor organs. Liver Transplantation 24 26–34 2018 AASLD.

The duration of asystolic ischemia determines the risk of graft failure after circulatory-dead donor kidney transplantation: A Eurotransplant cohort study

Circulatory death donor (DCD) kidney transplantations are steadily increasing. Consensus reports recommend limiting donor warm ischemia time (DWIT) in DCD donation, although an independent effect on graft outcome has not been demonstrated. We investigated death‐censored graft survival in 18 065 recipients of deceased‐donor kidney transplants in the Eurotransplant region: 1059 DCD and 17 006 brain‐dead donor (DBD) kidney recipients. DWIT was defined as time from circulatory arrest until cold flush. DCD donation was an independent risk factor for graft failure (adjusted hazard ratio [HR] 1.28, 95% CI 1.10‐1.46), due to an increased risk of primary nonfunction (62/1059 vs 560/17 006; P < .0001). With DWIT in the model, DCD donation was no longer a risk factor, demonstrating that DWIT explains the inferior graft survival of DCD kidneys. Indeed, DCD transplants with short DWIT have graft survival comparable to that of standard‐criteria DBD transplants (P = .59). DWIT also associated with graft failure in DCDs (adjusted HR 1.20 per 10‐minute increase, 95% CI 1.03‐1.42). At 5 years after transplantation, graft failure occurred in 14 of 133 recipients (10.5%) with DWIT <10 minutes, 139 of 555 recipients (25.0%) with DWIT between 10 and 19 minutes, and 117 of 371 recipients (31.5%) with DWIT ≥20 minutes. These findings support the expert opinion–based guidelines to limit DWIT.

Reconditioning by endischaemic hypothermic in-house machine perfusion: A promising strategy to improve outcome in ECD kidney transplantation

This clinical study evaluates end‐ischemic hypothermic machine perfusion (eHMP) in expanded criteria donors (ECD) kidneys. eHMP was initiated upon arrival of the kidney in our center and continued until transplantation. Between 11/2011 and 8/2014 eHMP was performed in 66 ECD kidneys for 369 (98‐912) minutes after 863 (364‐1567) minutes of cold storage (CS). In 49 of 66 cases, the contralateral kidney from the same donor was preserved by static CS only and accepted by another Eurotransplant (ET) center. Five (10.2%) of these kidneys were ultimately judged as “not transplantable” by the accepting center and discarded. After exclusion of early unrelated graft losses, 43 kidney pairs from the same donor were eligible for direct comparison of eHMP vs CS only: primary non‐function and delayed graft function (DGF) were 0% vs 9.3% (P=.04) and 11.6% vs 20.9% (P=.24). There was no statistically significant difference in 1‐year graft survival (eHMP vs CS only: 97.7% vs 88.4%, P=.089). In a multivariate analysis, eHMP was an independent factor for prevention of DGF (OR: 0.28, P=.041). Development of DGF was the strongest risk factor for 1‐year graft failure (Renal resistance: 38.2, P<.001). In summary, eHMP is a promising reconditioning technique to improve the quality and acceptance rate of suboptimal grafts.

Conscientious objection to deceased organ donation by healthcare professionals

In this article, we analyse the potential benefits and disadvantages of permitting healthcare professionals to invoke conscientious objection to deceased organ donation. There is some evidence that permitting doctors and nurses to register objections can ultimately lead to attitudinal change and acceptance of organ donation. However, while there may be grounds for conscientious objection in other cases such as abortion and euthanasia, the life-saving nature of donation and transplantation renders objection in this context more difficult to justify. In general, dialogue between healthcare professionals is a more appropriate solution, and any objections must be justified with a strong rationale in hospitals where such policies are put in place.