Does kidney transplantation with a standard or expanded criteria donor improve patient survival? Results from a Belgian cohort.

BACKGROUND: Changes in recipient and donor factors have reopened the question of survival benefits of kidney transplantation versus dialysis. METHODS: We analysed survival among 3808 adult Belgian patients waitlisted for a first deceased donor kidney transplant from 2000 to 2012. The primary outcome was mortality during the median waiting time plus 3 years of follow-up after transplantation or with continued dialysis. Outcomes were analysed separately for standard criteria donor (SCD) and expanded criteria donor (ECD) kidney transplants. We adjusted survival analyses for recipient age (20-44, 45-64 and ≥65 years), sex and diabetes as the primary renal disease. RESULTS: Among patients ≥65 years of age, only SCD transplantation provided a significant survival benefit compared with dialysis, with a mortality of 16.3% [95% confidence interval (CI) 13.2-19.9] with SCD transplantation, 20.5% (95% CI 16.1-24.6) with ECD transplantation and 24.6% (95% CI 19.4-29.5) with continued dialysis. Relative mortality risk was increased in the first months after transplantation compared with dialysis, with equivalent risk levels reached earlier with SCD than ECD transplantation in all age groups. CONCLUSIONS: The results of this study suggest that older patients might gain a survival benefit with SCD transplantation versus dialysis, but any survival benefit with ECD transplantation versus dialysis may be small.

Family overrule of registered refusal to donate organs.

It is well known that families frequently overrule the wishes of dying patients who had previously expressed a wish to donate their organs. Various strategies have been suggested to reduce the frequency of these 'family overrules'. However, the possibility of families overruling a patient's registered decision not to donate has not been discussed in the medical literature, although it is legally possible in some countries. In this article, we provide an ethical analysis of family overrule of a relative's refusal to donate, using the different jurisdictions of the UK, Switzerland, Germany and the Netherlands to provide some context. Despite some asymmetries between overruling consent and overruling refusal, there are some cases in which donation should proceed despite a recorded refusal to do so.

Accuracy of Pretransplant Imaging Diagnostic for Hepatocellular Carcinoma: A Retrospective German Multicenter Study.

Selection and prioritization of patients with HCC for LT are based on pretransplant imaging diagnostic, taking the risk of incorrect diagnosis. According to the German waitlist guidelines, imaging has to be reported to the allocation organization (Eurotransplant) and pathology reports have to be submitted thereafter. In order to assess current procedures we performed a retrospective multicenter analysis in all German transplant centers with focus on accuracy of imaging diagnostic and tumor classification. 1168 primary LT for HCC were conducted between 2007 and 2013 in Germany. Patients inside the Milan, UCSF, and up-to-seven criteria were misclassified with definitive histologic results in 18%, 15%, and 11%, respectively. Patients pretransplant outside the Milan, UCSF, and up-to-seven criteria were otherwise misclassified in 34%, 43%, and 41%. Recurrence-free survival correlated with classification by posttransplant histological report, but not pretransplant imaging diagnostic. Univariate analysis revealed tumor size, vascular invasion, and grading as significant parameters for outcome, while tumor grading was the only parameter persisting by multivariate testing. Conclusion. There was a relevant percentage (15-40%) of patients misclassified by imaging diagnosis at a time prior to LI-RADS and guidelines to improve imaging of HCC. Outcome analysis showed a good correlation to histological, in contrast poor correlation to imaging diagnosis, suggesting an adjustment of the LT selection and prioritization criteria.

Equally Interchangeable? How Sex and Gender Affect Transplantation.

Organ transplantation as an option to overcome end-stage diseases is common in countries with advanced healthcare systems and is increasingly provided in emerging and developing countries. A review of the literature points to sex- and gender-based inequity in the field with differences reported at each step of the transplant process, including access to a transplantation waiting list, access to transplantation once waitlisted, as well as outcome after transplantation. In this review, we summarize the data regarding sex- and gender-based disparity in adult and pediatric kidney, liver, lung, heart, and hematopoietic stem cell transplantation and argue that there are not only biological but also psychological and socioeconomic issues that contribute to disparity in the outcome, as well as an inequitable access to transplantation for women and girls. Because the demand for organs has always exceeded the supply, the transplant community has long recognized the need to ensure equity and efficiency of the organ allocation system. In the spirit of equity and equality, the authors call for recognition of these inequities and the development of policies that have the potential to ensure that girls and women have equitable access to transplantation.

The Impact of Hepatectomy Time of the Liver Graft on Post-transplant Outcome: A Eurotransplant Cohort Study.

OBJECTIVE: Assessing the effect of donor hepatectomy time on outcome after transplantation. SUMMARY OF BACKGROUND DATA: When blood supply in a deceased organ donor stops, ischemic injury starts. Livers are cooled to reduce cellular metabolism and minimize ischemic injury. This cooling is slow and livers are lukewarm during hepatectomy, potentially affecting outcome. METHODS: We used the Eurotransplant Registry to investigate the relationship between donor hepatectomy time and post-transplant outcome in 12,974 recipients of deceased-donor livers (January 1, 2004, to December 31, 2013). Cox regression analyses for patient and graft survival (censored and uncensored for death with a functioning graft) were corrected for donor, preservation, and recipient variables. Donor hepatectomy time was defined as time between start of aortic cold flush and placement of the liver in the ice-bowl. RESULTS: Median donor hepatectomy time was 41 minutes [interquartile range (IQR) 32 to 52]. Livers donated after circulatory death had longer hepatectomy times than those from brain-dead donors [50 minutes (35 to 68) vs 40 minutes (32 to 51), P < 0.001]. Donor hepatectomy time was independently associated with graft loss [adjusted hazard ratio (HR) 1.03 for every 10-minute increase, 95% confidence interval (95% CI) 1.02-1.05; P < 0.001]. The magnitude of this effect was comparable to the effect of each hour of additional cold ischemia time (adjusted HR 1.04, 95% CI 1.02-1.05; P < 0.001). Donor hepatectomy time had a similar effect on death-censored graft survival and patient survival. Livers donated after circulatory death and those with a higher donor risk index were more susceptible to the effect of donor hepatectomy time on death-censored graft survival. CONCLUSION: Donor hepatectomy time impairs liver transplant outcome. Keeping this time short together with efficient cooling during hepatectomy might improve outcome.

Outcome of Liver Transplant Patients With High Urgent Priority: Are We Doing the Right Thing?

BACKGROUND: About 15% of liver transplantations (LTs) in Eurotransplant are currently performed in patients with a high-urgency (HU) status. Patients who have acute liver failure (ALF) or require an acute retransplantation can apply for this status. This study aims to evaluate the efficacy of this prioritization. METHODS: Patients who were listed for LT with HU status from January 1, 2007, up to December 31, 2015, were included. Waiting list and posttransplantation outcomes were evaluated and compared with a reference group of patients with laboratory Model for End-Stage Liver Disease (MELD) score (labMELD) scores ≥40 (MELD 40+). RESULTS: In the study period, 2299 HU patients were listed for LT. Ten days after listing, 72% of all HU patients were transplanted and 14% of patients deceased. Patients with HU status for primary ALF showed better patient survival at 3 years (69%) when compared with patients in the MELD 40+ group (57%). HU patients with labMELD ≥45 and patients with HU status for acute retransplantation and labMELD ≥35 have significantly inferior survival at 3-year follow-up of 46% and 42%, respectively. CONCLUSIONS: Current prioritization for patients with ALF is highly effective in preventing mortality on the waiting list. Although patients with HU status for ALF have good outcomes, survival is significantly inferior for patients with a high MELD score or for retransplantations. With the current scarcity of livers in mind, we should discuss whether potential recipients for a second or even third retransplantation should still receive absolute priority, with HU status, over other recipients with an expected, substantially better prognosis after transplantation.

Optimizing the Use of Geriatric Livers for Transplantation in the Eurotransplant Region.

Acceptance criteria for liver allografts are ever more expanding because of a persisting wait-list mortality. Older livers are therefore offered and used more frequently for transplantation. This study aims to analyze the use and longterm outcome of these transplantations. Data were included on 17,811 first liver transplantations (LTs) and information on livers that were reported for allocation but not transplanted from 2000 to 2015 in the Eurotransplant (ET) region. Graft survival was defined as the period between transplantation and date of retransplantation or date of recipient death. In the study period, 2394 (13%) transplantations were performed with livers ≥70 years old. Graft survival was 74%, 57%, and 41% at 1-, 5-, and 10-year follow-up, respectively. A history of diabetes mellitus in the donor (hazard ratio [HR], 1.3; P = 0.01) and positive hepatitis C virus antibody in the recipient (HR, 1.5; P < 0.001) are specific risk factors for transplantations with livers ≥70 years old. Although donor age is associated with a linearly increasing risk of graft loss between 25 and 80 years old, no difference in graft survival could be observed when "preferred" recipients were transplanted with a liver <70 or ≥70 years old (HR 1.1; CI 0.92-1.23, P = 0.40) or with a donor <40 or ≥70 years old (HR 1.2; CI 0.96-1.37, P = 0.13). Utilization of reported livers ≥70 years old increased from 42% in 2000-2003 to 76% in 2013-2015 without a decrease in graft survival (P = 0.45). In conclusion, an important proportion of LTs in the ET region are performed with livers ≥70 years old. The risk of donor age on graft loss increases linearly between 25 and 80 years old. Livers ≥70 years old can, however, be transplanted safely in preferred patients and are to be used more frequently to further reduce wait-list mortality.

Association between donor age and risk of graft failure after liver transplantation: an analysis of the Eurotransplant database.

Grafts from elderly donors are increasingly used for liver transplantation. As of yet there is no published systematic data to guide the use of specific age cutoffs the effect of elderly donors on patient outcomes must be clarified. This study analyzed the Eurotransplant database (01/01/2000-31/07/2014; N = 26 294) out of whom 8341 liver transplantations were filtered to identify for this analysis. 2162 of the grafts came from donors >60 including 203 from octogenarians ≥80 years. Primary outcome was the risk of graft failure according to donor age using a confounder adjusted Cox-Regression model with frailty terms (or random effects). The proportion of elderly grafts increased during the study period [i.e., octogenarians 0.1% (n = 1) in 2000 to 3.4% (n = 45) in 2013]. Kaplan-Meier and Cox-analyses revealed a reduced survival and a higher risk for graft failure with increasing donor age. Although the age effect was allowed to vary non-linearly, a linear association hazard ratio (HR = 1.1 for a 10 year increase in donor age) was evident. The linearity of the association suggests that there is no particular age at which the effect increases more rapidly, providing no evidence for a cutoff age. In clinical practice, the combination of high donor age with HU-transplantations, hepatitis C, high MELD-scores and long cold ischemic time should be avoided.

The Impact of Implantation Time During Liver Transplantation on Outcome: A Eurotransplant Cohort Study.

BACKGROUND: The liver graft quickly rewarms during transplantation when the vascular anastomoses are being performed, potentially impacting on outcomes. METHODS: We investigated the relationship between implantation time and outcome in 5223 recipients of deceased-donor livers transplanted in Eurotransplant (2004-2013). Cox regression analyses were corrected for donor, preservation, and recipient variables. Transplant loss represents all-cause graft failure. RESULTS: Median implantation time was 41 minutes (interquartile range, 34-51). Implantation time independently associated with transplant loss (adjusted hazard ratio, 1.04 for every 10-minute increase; 95% confidence interval, 1.01-1.07; P = 0.007). The magnitude of the implantation time effect was comparable to the effect of each additional hour of cold ischemia (adjusted hazard ratio, 1.03; 95% confidence interval, 1.02-1.05; P < 0.001). The effect was most pronounced early posttransplant with no evidence of a significant effect beyond 3 months. A similar detrimental effect of implantation time was seen for graft and patient survivals. The increased risk for transplant loss in livers donated after circulatory determination of death could be attributed to donor warm ischemia time. CONCLUSIONS: Implantation time associates with inferior liver transplant outcome in a continuous way. These findings need confirmation and further study of confounding factors is needed so steps toward improving outcomes can be made.

The Effect of Histidine-tryptophan-ketoglutarate Solution and University of Wisconsin Solution: An Analysis of the Eurotransplant Registry.

BACKGROUND: Both University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are currently used in the Eurotransplant region for preservation of liver allografts. Previous studies on their effect have led to a lot of discussion. This study aims to compare the effect of HTK and UW on graft survival. METHODS: First liver transplantations in recipients 18 years or older from January 1, 2007, until December 31, 2016, were included. Graft survival was compared for livers preserved with HTK and UW at 30 days, 1, 3, and 5 years. Multivariable analysis of risk factors was performed and outcome was adjusted for important confounders. RESULTS: Of all 10 628 first liver transplantations, 8176 (77%) and 2452 (23%) were performed with livers preserved with HTK and UW, respectively. Kaplan-Meier curves showed significant differences in graft survival between HTK and UW at 30 days (89% vs 93%, P=<0.001), 1 year (75% vs 82%, P=<0.001), 3 years (67% vs 72%, P<0.001), and at 5 years (60% vs 67%, P<0.001). No significant differences in outcome were observed in separate analyses of Germany or non-German countries. In multivariable analysis, UW was associated with a decreased risk of graft loss at 30 days (HR 0.772, P=0.002) and at 1 year (0.847 (0.757-0.947). When adjusted for risk factors, no differences in long term outcome could be detected. CONCLUSIONS: Because the use of preservation fluids is clustered geographically, differences in outcome by preservation fluids are strongly affected by regional differences in donor and recipient characteristics. When adjusted for risk factors, no differences in graft survival exist between transplantations performed with livers preserved with either HTK or UW.

Heart re-transplantation in Eurotransplant.

Internationally 3% of the donor hearts are distributed to re-transplant patients. In Eurotransplant, only patients with a primary graft dysfunction (PGD) within 1 week after heart transplantation (HTX) are indicated for high urgency listing. The aim of this study is to provide evidence for the discussion on whether these patients should still be allocated with priority. All consecutive HTX performed in the period 1981-2015 were included. Multivariate Cox' model was built including: donor and recipient age and gender, ischaemia time, recipient diagnose, urgency status and era. The study population included 18 490 HTX, of these 463 (2.6%) were repeat transplants. The major indications for re-HTX were cardiac allograft vasculopathy (CAV) (50%), PGD (26%) and acute rejection (21%). In a multivariate model, compared with first HTX hazards ratio and 95% confidence interval for repeat HTX were 2.27 (1.83-2.82) for PGD, 2.24 (1.76-2.85) for acute rejection and 1.22 (1.00-1.48) for CAV (P < 0.0001). Outcome after cardiac re-HTX strongly depends on the indication for re-HTX with acceptable outcomes for CAV. In contrast, just 47.5% of all hearts transplanted in patients who were re-transplanted for PGD still functioned at 1-month post-transplant. Alternative options like VA-ECMO should be first offered before opting for acute re-transplantation.

Lung allocation score: the Eurotransplant model versus the revised US model - a cross-sectional study.

Both Eurotransplant (ET) and the US use the lung allocation score (LAS) to allocate donor lungs. In 2015, the US implemented a new algorithm for calculating the score while ET has fine-tuned the original model using business rules. A comparison of both models in a contemporary patient cohort was performed. The rank positions and the correlation between both scores were calculated for all patients on the active waiting list in ET. On February 6th 2017, 581 patients were actively listed on the lung transplant waiting list. The median LAS values were 32.56 and 32.70 in ET and the US, respectively. The overall correlation coefficient between both scores was 0.71. Forty-three per cent of the patients had a < 2 point change in their LAS. US LAS was more than two points lower for 41% and more than two points higher for 16% of the patients. Median ranks and the 90th percentiles for all diagnosis groups did not differ between both scores. Implementing the 2015 US LAS model would not significantly alter the current waiting list in ET.

The center effect in liver transplantation in the Eurotransplant region: a retrospective database analysis.

Apart from donor and recipient risk factors, the effect of center-related factors has significant impact on graft survival after liver transplantation (LT). To investigate this effect in Eurotransplant, a retrospective database analysis was performed, including all LT's in adult recipients (≥18 years) in the Eurotransplant region from 1.1.2007 until 31.12.2013. Additionally, a survey was sent out to all transplant centers requesting information on surgeons' experience and exposure. In total, 10 265 LT's were included (median follow-up 3.3 years), performed in 39 transplant centers. Funnel plots showed significant differences in graft survival between the transplant centers. After correction for donor and recipient risk, with the Eurotransplant donor risk index (ET-DRI) and the simplified recipient risk index (sRRI) and random effects, these differences diminished. Mean historical volume (in the preceding 5 years) was a significant (P < 0.001), nonlinear marker for graft survival in the multivariate analysis. This study demonstrates that funnel plots can be used for benchmarking purposes in LT. Case-mix correction can be performed with the use of the ET-DRI and sRRI. The center effect encompasses the entire complex process of preoperative workup, operation to follow-up.

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.

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.

Bridging the gap in heart transplantation.

PURPOSE OF REVIEW: Countries in Europe and in the USA are proclaiming their need for an objective allocation system that can cope with distribution of a scarce resource in a changing environment of an older donor and recipient population and of an increased number of patients on mechanical circulatory support, whose prospects are increasing. RECENT FINDINGS: The current heart allocation systems in Eurotransplant, France and the USA are all urgency tier systems, where within the same tier a first-come, first-served principle is applied. Both Eurotransplant and France are developing new heart allocation schemes that hinge on a benefit principle, thereby combining the prospects of patients after transplantation with their expected clinical course while on the waiting list. In the USA, a different approach has been chosen for their new allocation scheme, as the medical urgency of the patient is the driving force behind the proposal. SUMMARY: Policies to ensure a fair, efficient, and medically optimal matching of donor organs and recipients are continually evaluated and refined. The ethical cornerstone of each organ allocation policy in the described countries is the effort of balancing justice and utility.

Adult Liver Allocation in Eurotransplant.

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.