Eurotransplant Donor Risk Index Research Articles

Viability assessment and transplantation of extended criteria donor liver grafts using normothermic machine perfusion

BackgroundThe scarcity of available liver grafts necessitates the use of organs from extended criteria donors, a practice associated with an increased risk of graft failure. A notable percentage of deceased donor liver allografts are rejected due to subjective criteria. Normothermic machine perfusion holds promise for introducing objective parameters into this decision-making process. The aim of this study was to compare the outcomes of standard criteria and extended criteria donor allografts after liver transplantation, following viability assessment, using normothermic machine perfusion. MethodsLiver allografts preserved by normothermic machine perfusion before liver transplantation at the University Hospital of Münster were retrospectively analyzed. Organs were stratified according to the Eurotransplant Donor Risk Index. In total, 101 liver grafts were included in this study and divided into 2 groups: (1) standard criteria donors with a Donor Risk Index <1.8 (DRI-low) and (2) extended criteria donors with a Donor Risk Index ≥1.8 (DRI-high). ResultsAn increased risk profile of donor livers, as assessed by the Eurotransplant Donor Risk Index, did not correlate with patient or graft survival. High-risk liver grafts were effectively transplanted into recipients with different risk levels after viability assessment by normothermic machine perfusion. However, the recipients’ model for end-stage liver disease scores showed a significant association with both overall patient and graft survival. ConclusionThe use of normothermic machine perfusion for viability assessment allows safe transplantation of high-risk donor livers and effectively addresses the disparity between donor liver availability and transplantation demand.

Postoperative Outcomes in 415 Patients Following Liver Transplantation Using Extended Donor Criteria: A Study from a Single Center in Germany.

BACKGROUND Because of the massive organ shortage worldwide, marginal organs are increasingly being considered. The aim of this study was to present a comprehensive analysis of donor-related factors clinically supposed to influence the outcome after liver transplantation. This study from a single center in Germany aimed to evaluate postoperative outcomes in 415 patients following liver transplantation using extended donor criteria. MATERIAL AND METHODS Extended donor criteria (EDC) were considered according to the official guidelines issued through the German Medical Association. Other factors and the Eurotransplant Donor Risk Index (ET-DRI) were also considered. Correlation studies, logistic regression, and Kaplan-Meier-estimator were used to evaluate the outcome. RESULTS The postoperative outcomes with or without EDC were comparable. Other factors had an impact on early allograft failure (EAD), including male donors (χ²=14.135, P=0.0001). Other donor-unrelated factors, like cold ischemia time, also had an impact on EAD (r=0.135, P=0.010), especially in patients with model for end-stage liver disease (MELD) <25 (ß=0.001, P=0.008). ET-DRI was a crucial factor in estimating overall and allograft survival after liver transplantation. CONCLUSIONS The findings from this study support the possibility of liver transplantation using organs obtained by EDC. Other factors, like donor sex and cold ischemic time, are not part of the EDC, although they have an impact on EAD. Organs obtained by EDC continue to be an option to address the organ shortage.

Validation of risk scores for allograft failure after liver transplantation in Germany: a retrospective cohort analysis.

A growing number of clinical risk scores have been proposed to predict allograft failure after liver transplantation. However, validation of currently available scores in the Eurotransplant region is still lacking. We aimed to analyze all clinically relevant donor and recipient risk scores on a large German liver transplantation data set and performed a retrospective cohort analysis of liver transplantations performed at the Charité-Universitätsmedizin Berlin from January 2007 until December 2021 with organs from donation after brain death. We analyzed 9 previously published scores in 906 liver transplantations [Eurotransplant donor risk index (ET-DRI/DRI), donor age and model for end-stage liver disease (D-MELD), balance of risk (BAR), early allograft dysfunction (EAD), model for early allograft function (MEAF), liver graft assessment following transplantation (L-GrAFT7), early allograft failure simplified estimation (EASE), and a score by Rhu and colleagues). The EASE score had the best predictive value for 3-month, 6-month, and 12-month graft survival with a c-statistic of 0.8, 0.77, and 0.78, respectively. In subgroup analyses, the EASE score was suited best for male recipients with a high-MELD (>25) and an EAD organ. Scores only based on pretransplant data performed worse compared to scores including postoperative data (eg, ET-DRI vs. EAD, p<0.001 at 3-month graft survival). Out of these, the BAR score performed best with a c-statistic of 0.6. This a comprehensive comparison of the clinical utility of risk scores after liver transplantation. The EASE score sufficiently predicted 12-month graft and patient survival. Despite a relatively complex calculation, the EASE score provides significant prognostic value for patients and health care professionals in the Eurotransplant region.

Invasive Fungal Infections After Liver Transplantation: A Retrospective Matched Controlled Risk Analysis.

BackgroundInvasive fungal infections (IFI) are major risks for mortality after liver transplantation (LT). The aim of this study was to evaluate possible risk factors for the development of IFI after LT.Material/MethodsAll adult patients with IFI after LT between January 2012 and December 2016 at Essen University were identified. Pre-, intra-, and postoperative data were reviewed. These were compared to a 1-to-3 matched control group. Multinominal univariate and multivariate regression analyses were performed.ResultsOut of the 579 adults who underwent LT, 33 (5.6%) developed postoperative IFI. Fourteen had invasive aspergillosis with 7 (50%) mortality, and 19 had Candida sepsis with 7 (37%) mortality. The overall mortality due to invasive fungal infections was 42%. Perfusion fluid contamination with yeast was detected in 5 patients (15%). Multivariate regression analyses showed that preoperative dialysis (OR=1.163; CI: 1.038–1.302), Eurotransplant donor risk index (OR=0.04; CI=0.003–0.519), length of hospital stay (OR=25.074; CI: 23.99–26.208), and yeast contamination of the preservation fluid (OR=47.8; CI: 4.77–478, 96) were associated with IFI in the Candida group, whereas duration of surgery (OR=1.013; CI: 1.005–1.022), ventilation hours (OR=0.993; CI=0.986–0.999), and days of postoperative dialysis (OR=1.195; CI: 1.048–1,362) were associated with IFI in the aspergillosis group.ConclusionsPost-LT IFI had 42% mortality in our cohort. Prophylactic antifungal therapy should be expanded to broader risk groups as defined above.

Prognostic role of the Donor Risk Index, the Eurotransplant Donor Risk Index, and the Balance of Risk score on graft loss after liver transplantation.

This study aimed to identify cutoff values for donor risk index (DRI), Eurotransplant (ET)-DRI, and balance of risk (BAR) scores that predict the risk of liver graft loss. MEDLINE and Web of Science databases were searched systematically and unrestrictedly. Graft loss odds ratios and 95% confidence intervals were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Cutoff values for predicting graft loss at 3months, 1year, and 3years were analyzed for each of the scores. Measures of calibration and discrimination used in studies validating the DRI and the ET-DRI were summarized. DRI≥1.4 (six studies, n=35580 patients) and ET-DRI≥1.4 (four studies, n=11666 patients) were associated with the highest risk of graft loss at all time points. BAR>18 was associated with the highest risk of 3-month and 1-year graft loss (n=6499 patients). A DRI cutoff of 1.8 and an ET-DRI cutoff of 1.7 were estimated using a summary receiver operator characteristic curve, but the sensitivity and specificity of these cutoff values were low. A DRI and ET-DRI score≥1.4 and a BAR score>18 have a negative influence on graft survival, but these cutoff values are not well suited for predicting graft loss.

Model for end-stage liver disease score predicts complications after liver transplantation.

Increased model for end-stage liver disease (MELD) score measured in the early postoperative course is associated with one-year mortality and graft loss. However, the correlation with postoperative complications has not been investigated. The aim of this study was to investigate the association between postoperative MELD score and subsequent complications. Adult liver transplant recipients transplanted from January 2011 until December 2016 were included. MELD score days 1-5 were correlated with complications day 6-30, subdivided into type and severity according to Clavien-Dindo classification. We included 246 adult liver transplant recipients. Between days 6 and 30, 671 complications occurred in 201 of the patients (82%) corresponding to 64% of all postoperative complications in the whole postoperative period (days 0-30). In multivariate analyses adjusted for recipient gender and age, preoperative MELD score, and Eurotransplant Donor Risk Index, postoperative MELD score was significantly associated with having one or more complications, any type of complication except cardiovascular and renal complications, and complication severity. Postoperative MELD score days 1-5 were associated with complications arising in the subsequent period 6-30 days after transplantation. An increased MELD score should heighten the clinician's awareness of a possible complication.

Development and Validation of a Comprehensive Model to Estimate Early Allograft Failure Among Patients Requiring Early Liver Retransplant

Expansion of donor acceptance criteria for liver transplant increased the risk for early allograft failure (EAF), and although EAF prediction is pivotal to optimize transplant outcomes, there is no consensus on specific EAF indicators or timing to evaluate EAF. Recently, the Liver Graft Assessment Following Transplantation (L-GrAFT) algorithm, based on aspartate transaminase, bilirubin, platelet, and international normalized ratio kinetics, was developed from a single-center database gathered from 2002 to 2015. To develop and validate a simplified comprehensive model estimating at day 10 after liver transplant the EAF risk at day 90 (the Early Allograft Failure Simplified Estimation [EASE] score) and, secondarily, to identify early those patients with unsustainable EAF risk who are suitable for retransplant. This multicenter cohort study was designed to develop a score capturing a continuum from normal graft function to nonfunction after transplant. Both parenchymal and vascular factors, which provide an indication to list for retransplant, were included among the EAF determinants. The L-GrAFT kinetic approach was adopted and modified with fewer data entries and novel variables. The population included 1609 patients in Italy for the derivation set and 538 patients in the UK for the validation set; all were patients who underwent transplant in 2016 and 2017. Early allograft failure was defined as graft failure (codified by retransplant or death) for any reason within 90 days after transplant. At day 90 after transplant, the incidence of EAF was 110 of 1609 patients (6.8%) in the derivation set and 41 of 538 patients (7.6%) in the external validation set. Median (interquartile range) ages were 57 (51-62) years in the derivation data set and 56 (49-62) years in the validation data set. The EASE score was developed through 17 entries derived from 8 variables, including the Model for End-stage Liver Disease score, blood transfusion, early thrombosis of hepatic vessels, and kinetic parameters of transaminases, platelet count, and bilirubin. Donor parameters (age, donation after cardiac death, and machine perfusion) were not associated with EAF risk. Results were adjusted for transplant center volume. In receiver operating characteristic curve analyses, the EASE score outperformed L-GrAFT, Model for Early Allograft Function, Early Allograft Dysfunction, Eurotransplant Donor Risk Index, donor age × Model for End-stage Liver Disease, and Donor Risk Index scores, estimating day 90 EAF in 87% (95% CI, 83%-91%) of cases in both the derivation data set and the internal validation data set. Patients could be stratified in 5 classes, with those in the highest class exhibiting unsustainable EAF risk. This study found that the developed EASE score reliably estimated EAF risk. Knowledge of contributing factors may help clinicians to mitigate risk factors and guide them through the challenging clinical decision to allocate patients to early liver retransplant. The EASE score may be used in translational research across transplant centers.

Preoperative Assessment of Muscle Mass Using Computerized Tomography Scans to Predict Outcomes Following Orthotopic Liver Transplantation.

Sarcopenia is an established risk factor predicting survival in chronically ill and trauma patients. We herein examine the assessment and clinical implication of sarcopenia in liver transplantation (LT). Computerized tomography scans from 172 patients waitlisted for LT were analyzed by applying 6 morphometric muscle scores, including 2 density indices (psoas density [PD] and skeletal muscle density [SMD]) and 4 scores based on muscle area (total psoas area, psoas muscle index, skeletal muscle area, and skeletal muscle index). The prevalence of sarcopenia in our cohort ranged from 7.0% to 37.8%, depending on the score applied. Only sarcopenia as defined by the density indices PD and SMD (but not total psoas area, psoas muscle index, skeletal muscle area, or skeletal muscle index) revealed clinical relevance since it correlates significantly with postoperative complications (≥Grade III, Clavien-Dindo classification) and sepsis. Furthermore, sarcopenia predicted inferior patient and graft survival, with low muscle density (PD: <38.5 HU or SMD: <30 HU) representing an independent risk factor in a multivariate regression model (P < 0.05). Importantly, the widely used Eurotransplant donor risk index had a predictive value in nonsarcopenic patients but failed to predict graft survival in patients with sarcopenia. Sarcopenia revealed by low muscle density correlates with major complications following LT and acts as an independent predictor for patient and graft survival. Therefore, the application of a simple computerized tomography-morphologic index can refine an individual recipient's risk estimate in a personalized approach to transplantation.

Graft Risk Index After Liver Transplant: Internal and External Validation of a New Spanish Indicator.

Scarcity of liver grafts has led to the use of marginal donors, consequently increasing the number of complications posttransplant. To prevent this situation, several indicators have been developed. However, important differences remain among countries. Here, we compared an early-risk liver transplant indicator based on the Spanish Liver Transplant Registry, called the Graft Risk Index, versus the US donor risk index and the Eurotransplant donor risk index. The new indicator was based on prospectively collected data from 600 adult liver transplants performed in our center. We considered 2 events to compare the indexes: graft survival and rejection-free graft survival, with Cox proportional regression for analyses. Power to predict graft survival was evaluated by calculating the receiver operating characteristic area under the curve. We found no differences between the US and Eurotransplant donor risk indexes in prediction of patients with and without early graft failure. With regard to early survival, only the Graft Risk Index allowed better survival discrimination, in which survival progressively decreased with values ≥ 3 (with probability of graft survival at 1 month of 68%; 95% confidence interval, 46.2-82.5). This increase in risk was significant compared with the standard group (hazard ratio of 10.15; 95% confidence interval, C 3.91- 26.32; P < .001). We calculated powers of prediction of 0.52 (95% confidence interval, 0.43-0.62), 0.54 (95% confidence interval, 0.45-0.65), and 0.69 (95% confidence interval, 0.61-0.77) for donor risk index, Eurotransplant donor risk index, and early Graft Risk Index, respectively. Neither the US donor risk index nor the Eurotransplant donor risk index was valid for our Spanish liver donation and transplant program. Therefore, an indicator to predict posttransplant graft survival that is adapted to our environment is necessary. This national Graft Risk Index can be a useful tool to optimize donor-recipient matching.

Potential value and limitations of different clinical scoring systems in the assessment of short- and long-term outcome following orthotopic liver transplantation.

BackgroundIn an attempt to further improve liver allograft utilization and outcome in orthotopic liver transplantation (OLT), a variety of clinical scoring systems have been developed. Here we aimed to comparatively investigate the association of the Balance-of-Risk (BAR), Survival-Outcomes-Following-Liver-Transplant (SOFT), Preallocation-Survival-Outcomes-Following-Liver-Transplant (pSOFT), Donor-Risk-Index (DRI), and the Eurotransplant-Donor-Risk-Index (ET-DRI) scores with short- and long-term outcome following OLT.MethodsWe included 338 consecutive patients, who underwent OLT in our institution between May 2010 and November 2017. For each prognostic model, the optimal cutoff values were determined with the help of the Youden-index and their diagnostic accuracy for 90-day post OLT-mortality and major postoperative complications was measured by the area under the receiver operating characteristic curve (AUROC). Patient- and graft survival were analyzed using the Kaplan-Meier method and the log-rank test. Morbidity was assessed using the Clavien-Dindo classification and the Comprehensive-Complication-Index.ResultsBAR, SOFT, and pSOFT performed well above the conventional AUROC-threshold of 0.70 with good prediction of early mortality. Only BAR showed AUC>0.70 for both mortality and major morbidity. With the cutoffs of 14, 31, and 22 respectively for BAR, SOFT, and pSOFT, subgroup analysis showed significant differences (p<0.001) in morbidity and mortality, length of intensive care- and hospital-stay and early allograft dysfunction rates. Five-years patient survival was inferior in the high BAR, pSOFT, and SOFT groups.ConclusionsOut of all scores tested, the BAR-score had the best value in predicting both 90-day morbidity and mortality after OLT showing the highest AUCs. The pSOFT and SOFT scores demonstrated an acceptable accuracy in predicting 90-day morbidity and mortality. The used BAR, SOFT, and pSOFT cutoffs allowed the identification of patients at risk in terms of five-year patient survival. The DRI and ET-DRI scores have failed to predict recipient outcomes in the present setting.

Identification and Validation of the Predictive Capacity of Risk Factors and Models in Liver Transplantation Over Time.

Outcome after liver transplantation (LT) is determined by donor, transplant and recipient risk factors. These factors may have different impact on either patient or graft survival (outcome type). In the literature, there is wide variation in the use of outcome types and points in time (short term or long term). Objective of this study is to analyze the predictive capacity of risk factors and risk models in LT and how they vary over time and per outcome type. All LTs performed in the Netherlands from January 1, 2002, to December 31, 2011, were analyzed with multivariate analyses at 3-month, 1-year, and 5-year for patient and (non-)death-censored graft survival. The predictive capacity of the investigated risk models was compared with concordance indices. Recipient age, model for end-stage liver disease sodium, ventilatory support, diabetes mellitus, hepatocellular carcinoma, previous malignancy, hepatitis C virus antibody, hepatitis B virus antibody, perfusion fluid, and Eurotransplant donor risk index (ET-DRI) had significant impact on outcome (graft or patient survival) at 1 or multiple points in time. Significant factors at 3-month patient survival (recipient age, model for end-stage liver disease sodium, ventilatory support) were used to compose a concept model. This model, had a higher c-index than the balance-of-risk score, DRI, ET-DRI, donor-recipient model and simplified recipient risk index for long-term patient and non-death-censored graft survival. In this study, the effects of recipient risk factors and models on different outcome types and time points were shown. Short-term patient survival mainly depends on recipient risk factors, long-term graft survival on donor risk factors and is more difficult to predict. Next to the concept model, the donor-recipient model has a higher predictive capacity to other risk models for (long-term) patient and non-death-censored graft survival. The DRI and ET-DRI best predicted death-censored graft survival. Knowledge about risk factors and models is critical when using these for waitlist management and/or help in organ allocation and decision-making.

A Donor Quality Index for liver transplantation: development, internal and external validation

Organ shortage leads to using non-optimal liver grafts. Thus, to determine the graft quality, the Donor Risk Index and the Eurotransplant Donor Risk Index have been proposed. In a previous study we showed that neither could be validated on the French database. Our aim was then dedicated to propose an adaptive Donor Quality Index (DQI) using data from 3961 liver transplantation (LT) performed in France between 2009 and 2013, with an external validation based on 1048 French LT performed in 2014. Using Cox models and three different methods of selection, we developed a new score and defined groups at risk. Model performance was assessed by means of three measures of discrimination corrected by the optimism using a bootstrap procedure. An external validation was also performed in order to evaluate its calibration and discrimination. Five donor covariates were retained: age, cause of death, intensive care unit stay, lowest MDRD creatinine clearance, and liver type. Three groups at risk could be discriminated. The performances of the model were satisfactory after internal validation. Calibration and discrimination were preserved in the external validation dataset. The DQI exhibited good properties and is potentially adaptive as an aid for better guiding decision making for LT.

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 (≥18years) 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, 10265 LT's were included (median follow-up 3.3years), 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 5years) 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.

External validation of the Donor Risk Index and the Eurotransplant Donor Risk Index on the French liver transplantation registry.

A major limitation to liver transplantation is organ shortage leading to the use of non-optimal liver grafts. The Donor Risk Index has been validated and recommended to select donors/organs. The Eurotransplant Donor Risk Index was derived from the Donor Risk Index. The objective of our study was to perform an external validation of both Donor Risk Index and Eurotransplant-Donor Risk Index against the French liver transplantation Cristal registry according to recommendations of the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis. Liver transplantations performed in France between 2009 and 2013 were used to perform the validation study for the Donor Risk Index and the Eurotransplant-Donor Risk Index respectively. We applied on the French data the models used to construct the Donor Risk Index and the Eurotransplant-Donor Risk Index respectively. Neither the Donor Risk Index nor the Eurotransplant-Donor Risk Index were validated against this dataset. Discrimination and calibration of these scores were not preserved according to our data. Important donor and candidates differences between our dataset and the Organ Procurement and Transplantation Network or the Eurotransplant datasets may explain why the Donor Risk Index and the Eurotransplant-Donor Risk Index appeared unadapted to the French transplant registry. Neither of these risk indexes were suitable to optimize the French liver allocation system. Thus, our next step will be to propose a general adaptive model for a Donor Risk Index.

Flushing the liver with urokinase before transplantation does not prevent nonanastomotic biliary strictures.

The aim of the present study was to assess whether flushing the donor liver with urokinase immediately before implantation reduces the incidence of nonanastomotic biliary strictures (NASs) after liver transplantation, without causing increased blood loss, analyzed as a historical cohort study. Between January 2005 and October 2012, all liver (re-)transplantations were included. Of the 185 liver transplant recipients included, 63 donor livers between January 2010 and October 2012 received urokinase (study group), whereas the donor liver of 122 consecutive recipients, who served as a historical control group, between January 2005 and January 2010 did not receive urokinase. Basic donor (Eurotransplant donor risk index) and recipient (age, body mass index, laboratory Model for End-Stage Liver Disease score) characteristics did not significantly differ in both groups. Thirty-three recipients developed NASs: 22 in the control group (18%) and 11 (17.5%) in the study group (P = 0.68). Analyzed separately for donation after circulatory death (P = 0.42) or donation after brain death (P = 0.89), there was no difference between the groups in incidence of NAS. Of all the recipients developing NAS, 7 (21%) needed retransplantation and all others were treated conservatively. Autologous blood transfusion requirements did not differ significantly between both groups (P = 0.91), whereas interestingly, more heterologous blood transfusions were needed in the control group (P < 0.001). This study has its limitations by its retrospective character. A multi-institutional prospective study could clarify this issue. In conclusion, arterial flushing of the liver with urokinase immediately before implantation did not lead to a lower incidence of NAS in this study, nor did it lead to increased blood loss.

Evaluating twenty-years of follow-up after orthotopic liver transplantation, best practice for donor-recipient matching: What can we learn from the past era?

AIMTo characterize major determinants of 20-year survival after liver transplantation (LT).METHODSThis longitudinal single-institution study includes 313 consecutive patients who received a LT between 1988 and 1992. Pretransplant clinical characteristics and laboratory values were assessed and compared between 20-year survivors and non-survivors. Particular attention was paid to the Model for End-Stage Liver Disease (labMELD)-score and the Eurotransplant Donor Risk Index (ET-DRI) to unravel their impact on 20-year survival after LT.RESULTSTwenty-year survivors were significantly younger (44 vs 50 years, P = 0.001), more likely to be female (49% vs 36%, P = 0.03) and less likely to be obese at the time of LT (19% vs 32%, P = 0.011). Mean labMELD-score (P = 0.156), rate of high-urgency LT (P = 0.210), cold-ischemia time (P = 0.994), rate of retransplantation (P = 0.12) and average donor age (28 vs 33 years, P = 0.099) were not statistically different. The mean estimated glomerular filtration rate was higher among survivors (P = 0.007). ET-DRI > 1.4 (P = 0.020) and donor age ≥ 30 years (P < 0.022) had significant influence on 20-year survival. The overall survival was not significantly impacted by labMELD-score categories (P = 0.263).CONCLUSIONLT offers excellent long-term results in case of optimal donor and recipient conditions. However, mainly due to the current organ shortage, these ideal circumstances are rarely given; thus algorithms for donor-recipient matching need to be refined, in order to enable a maximum benefit for the recipients of high quality as well as marginal organs.

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.

The Combination of ET-DRI and Recipient Risk Factors Is Predictive of Graft Failure After Liver Transplantation Within the Eurotransplant Region.

INTRODUCTION The Eurotransplant Donor Risk Index (ET-DRI) is a donor risk model predictive of graft failure after liver transplantation. Obviously, a combination of donor and recipient risk would be more complete in predicting outcome. Currently such a model does not exist for the Eurotransplant region. OBJECTIVE Investigation of the predictive value of the combination of donor risk (ET-DRI) and recipient risk (RRI) as a predictive model of outcome after liver transplantation. METHODS All liver transplants within the Eurotransplant region in adult (≥18) recipients from 1.1.2008 till 31.12.2010 were analysed. A simplified RRI was created using all available recipient factors (age, sex, cause of ESLD, MELD, urgency status and retransplant status). RESULTS A total of 4466 liver transplants were performed. Median donor age was 53 years and most frequent cause of death (COD) was by CVA (62%). Median CIT was 9 hours and 25% of all transplants were performed with a rescue organ. Median DRI and ET-DRI were 1.78 and 1.82 respectively. Median recipient age was 55 years and most frequent cause of ESLD was alcoholic cirrhosis (24%), followed by patients with a malignant liver disease (21%). Patients were mainly transplanted according to their lab-MELD score (72%). Median lab-MELD was 23. The ET-DRI was highly significant in the Cox-regression analysis, correcting for recipient factors (Log-Rank test p<0.001; c-index 0.54). A second analysis of the combination of the ET-DRI with MELD gave a strong correlation with outcome (Log-Rank p<0.001; c-index 0.58). Finally, all recipient factors were used to create a simplified RRI. This simplified RRI and ET-DRI were divided into three categories (low, medium, high). The combination of these two risk indices gave nine values, that were stronger correlated with outcome after OLT as compared to MELD-ET-DRI (Log-Rank p<0.001; c-index 0.71). The most hazardous combination (high-RRI with high-ET-DRI) had a HR of 5.5 as compared to the reference combination (low RRI-low ET-DRI). CONCLUSION The combination of the ET-DRI with a simplified RRI is a very significant, predictive model of graft failure after liver transplantation. Potentially this model could also be used as a tool for liver allocation.

The Ideal LT-Recipient - Single Center Experience From Two Decades Long Term Follow-Up.

Introduction: Organ shortage has led to implementation of different liver allocation policies and use of marginal organs. This study characterizes patients that benefit most from LT regarding survival. The impact of Model of End-Stage Liver Disease (MELD)-score and Eurotransplant Donor Risk Index (ET-DRI) on long-term survival are described. Methods: A longitudinal single-institution study was performed. Between 1988 and 1992, 337 LT were conducted in 313 patients. Pretransplant clinical characteristics and laboratory values were assessed and compared between 20-year LT survivors and non-survivors. Furthermore, the labMELD-score was calculated and the ET-DRI was determined for the donor organs and their impact on long-term survival was analyzed. Results: 20-year survivors were significantly younger (44 vs. 50 years, p<0.001), included less recipients over 55 years (12% vs. 26%, p=0.003), more females (49% vs. 36%, p=0.03), had a lower mean BMI (22.7 vs. 23.5, p=0.037) and a lower prevalence of obesity (19% vs. 32%, p=0.016). There were no statistically significant differences regarding MELD-score (p=0.156), rate of urgent LT (p=0.127), coldischemia time (p=0.994), rate of retransplantation (p=0.12) as well as pretransplant laboratory parameters. The mean estimated glomerular filtration rate was higher among survivors (p=0.007), but the number of patients with impaired renal function was not significantly lower. Mean donor age was lower in survivors (42 vs. 49 years, p<0.001) and mean ET-DRI was lower (1.32 vs. 1.37, p=0.121). ET-DRI scores of 1 to 1.2, 1.21 to 1.4 and >1.4 led to survival outcomes of 94.1%, 90% and 82.4% at 1 year, 90.2%, 80.0% and 69.1% at 5 years, 86.3%, 71.5% and 60.3% at 10 years and 59.7%, 56.9% and 37.6% at 20 years (p= 0.033). survival at 1, 5, 10 and 20 years was 94%, 91%, 89% and 76% for those receiving donor organs <30 (n=56), 89%, 79%, 73% and 54% for the group 31-55 (n=211) and 88%, 81%, 61% and 36% for donor organs >55 (n=57) (p<0.001). Patients without HBMI showed significantly better overall 20-year survival (58% vs. 42%, p=0.007). Survival was not significantly impacted by MELD-score categories. Conclusion: Excellent long-term results after LT are feasible. Precise donor-recipient matching is crucial for acceptable survival and waitlist-mortality, especially when allocating extended-criteria donor organs to sicker patients.

Post-Transplant MELD Score Predicts Mortality and Re-Transplantation Among Liver Transplant Recipients.

Introduction: Predictors of outcome after liver transplantation (LTx) remain poorly defined. The MELD score reflects the degree of liver disease, but the pre-transplantation MELD score does not predict death after LTx. We explored the predictive ability of continuous determinations of the post-transplant MELD score on the risk of death or re-LTx. Methods: Patients receiving a deceased donor liver transplantation from 2007 to October 2013 at our center were characterized according to MELD score prior to and 14 days after LTx, and 1-year re-TX or death status after transplantation was ascertained. The risk of this outcome was assessed according to quartiles of MELD in Cox models adjusted for age, gender, fulminant hepatic failure and EuroTransplant Donor Risk Index. Results: 254 patients received a liver transplantation of whom 30 died and 8 required re-LTx. The hazard ratio (HR) of death/re-Tx for patients in highest (Q4) versus lowest quartile (Q1) of MELD determined at varying times relative to date of transplantation: 2.8 (95% CI: 1.0-7.9) just prior to LTx, 4.2 (1.6-11.2) 1 day and 11.7 (2.8-50.1) 14 days after (see fig 1 for Kaplan-Meier estimated according to MELD quartiles at day 14). The predicted risk of death/re-Tx for MELD at day 14 (adjusted HR(Q4 vs rest of cohort)=8.3 (3.5-19.5)) was not affected by further adjustment for changes in the MELD score from previous days to day 14, nor by introducing the biochemical variables at day 14 upon which the MELD score is calculated. Conclusion: The MELD score determined 14 days after liver transplantation is a strong predictor of survival or re-Tx after liver transplantation. The predictive ability is not affected by changes in MELD upto that day, and is a stronger predictor than each of the components it is constructed from. Future studies should focus on identifying reasons for post-transplant MELD score elevations, and identify novel strategies for intervention in recipients with a high score.Figure: No Caption available.