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.

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.

Impact of dynamic changes in MELD score on survival after liver transplantation - a Eurotransplant registry analysis.

BACKGROUND & AIMS: With restricted numbers of available organs, futility in liver transplantation has to be avoided. The concept of dynamic changes in MELD score (DeltaMELD) has previously been shown to be a simple tool to identify patients with the greatest risk of death after transplantation. Aim was to validate this concept with the Eurotransplant (ET) database. METHODS: A retrospective registry analysis was performed on all patients listed for liver transplantation within ET between 2006 and 2011. Patients <18 years of age, acute liver failure, malignancy and patients listed for retransplantation were excluded. Influence of MELD at listing (MELDon), MELD at transplantation (MELDoff), DeltaMELD, age, sex, underlying disease and time on the waiting list on overall survival after liver transplantation were evaluated. RESULTS: A total of 16 821 patients were listed for liver transplantation, 8096 met the inclusion criteria. Age, MELD on and DeltaMELD showed significant influence on survival on the waiting list. Age and DeltaMELD showed influence on survival after liver transplantation, with DeltaMELD>10 showing a 1.6-fold increased risk of death. CONCLUSION: The concept of DeltaMELD was validated in a large, prospective data set. It provides a simple tool to identify patients with increased risk of death after liver transplantation and might help improve long-term results.

Donor scoring system for heart transplantation and the impact on patient survival.

BACKGROUND: The aim of this study was to design and validate a heart donor score that reflects experts' perceived risk of allograft failure. METHODS: All heart donors reported to Eurotransplant between January 1, 2005 and December 31, 2008 (N = 4,110) were used to create a donor score. Based on observed discard rates and using multivariate regression, points were assigned for the following donor factors: age; cause of death; body mass index (BMI); diabetes mellitus (DM); duration of ICU stay; compromised history (drug, abuse, sepsis, meningitis, malignancy, HBsAg(+) or anti-HCV(+)); hypertension; cardiac arrest; echocardiography; coronary angiogram; serum sodium; and noradrenaline and dopamine/dobutamine doses. The donor score was obtained by adding all points. All heart donors reported to Eurotransplant in 2009 were included to validate the score (N = 885). RESULTS: All donor factors, except BMI, DM and duration of ICU stay, significantly predicted discard. Based on the median value of the score, donors were classified into low-risk donors (LRDs: ≤16 points) and high-risk donors (HRDs: ≥17 points). In the validation set, discard rates were significantly different when comparing HRDs (35%) and LRDs (7%) (p < 0.0001). In addition, the heart donor score was significantly associated with 3-year survival: LRD 81.5% vs HRD 70.0% (p = 0.004). CONCLUSIONS: The heart donor score accurately reflects the likelihood of organ acceptance and predicts long-term patient mortality. Application of this score at time of donor reporting may facilitate donor risk assessment and allow for more appropriate matching of extended criteria donor hearts.

Defining an extended criteria donor lung: an empirical approach based on the Eurotransplant experience.

The aim of this study was to design and validate a lung donor score that reflects experts' perceived risk of allograft failure. All lung donors reported to Eurotransplant from 1999 to 2007 [N=6080] were used to create a lung donor score. Based on observed discard rates and using multivariate regression, points were assigned for six preprocurement donor variables. Donors reported in 2008 were used to validate the score [N=751]. All the six factors significantly predicted discard; as an example, the following donor with points: age 55-59years: 2; compromised history: 4; smoking: 2; shadow on chest X-ray: 2; purulent secretion during bronchoscopy: 2; and Pao(2) /Fio(2) ratio below 300mmHg: 3. Discard rates for donors with a lung donor score of 6 points (class 1) was 18%, while 36% and 54% of the donors with a score of 7-8 (class 2) and 9+(class 3) were discarded (P<0.001), respectively. In addition, the donor lung score was significantly associated with 1-year survival: class 1: 91%; class 2: 80%; and class 3: 72% (P=0.017). The lung donor score accurately reflects the likelihood of organ acceptance and predicts patient mortality, and its application at time of donor reporting may facilitate donor risk assessment and patient selection.

Three-year survival rates for all consecutive heart-only and lung-only transplants performed in Eurotransplant, 1997-1999.

The definition of proper patient selection criteria remains a prominent item in constant need of attention. While the concept of gathering evidence in order to determine practice continues to be hopelessly ambiguous, it can never be emphasized too much that these univariate results are just a first foray into analysing predictors of survival; all following results should be regarded and interpreted in this perspective. HEART TRANSPLANT SURVIVAL: The 3-year survival rate for heart transplant recipients under age 16 was 83% versus 72% for adult recipients. Acutely retransplanted adult heart recipients had a 3-year survival rate of 36% compared with 72% for recipients of a first heart allograft. Patients suffering from DCM had the best survival rates at 3 years (74%) compared with patients suffering from CAD (70%) or from another end-stage heart disease (67%). With advancing age of the adult recipient, the mortality risk increased. Patients aged 16-40 had a 3-year survival rate of 77%, compared with 74%, 70% and 61% for transplant recipients aged 41-55, 56-65 and over age 65, respectively. The 3-year survival rates for adult recipients transplanted with an heart allograft from a donor aged under 16 or between 16-44 were 78% and 74%, compared with 66% and 63% for donors aged 45-55 and over 55, respectively. The 3-year survival rates for recipients of hearts with cold ischemic times under 2 hours, 2-3, 3-4, 4-5, 5-6 and more than 6 hours were 74%, 75%, 70%, 65%, 54% and 40%, respectively. Transplanting a female donor heart into a male recipient was associated with the worst prognosis: the 3-year survival rates were 73%, 71%, 66% and 76%, respectively, for the donor/recipient groups male/male, male/female, female/male and female/female, respectively. When the donor-to-recipient body weight ratio was below 0.8, the 3-year survival rate was 64%, compared to 72% for weight-matched pairs and 74% for patients who received a heart from an oversized donor (p=0.004). Better survival rates were obtained for better HLA-matched transplants. The 3-year survival rates were 75%, 89%, 78%, 78%, 69%, 72%, and 71% for HLA-A,-B,-DR zero, 1, 2, 3, 4, 5 and 6 mismatched groups, respectively (p=0.04). Survival was significantly associated with the CMV serologic status of the donor and recipient; the 3-year survival rates were: D+/R+, 71%; D+/R-, 69%; D- R-, 76%; and D-/R+, 76% (p=0.04). Patients in an ICU had a 3-year survival rate of 62%, compared to 72% for patients in a general ward and 74% for outpatients (p<0.0001). Patients that were on a VAD and there-upon transplanted had a 3-year survival rate of 65%, compared to 73% for patients without a VAD (p=0.004). Being on a ventilator was a major risk factor for death after transplantation; patients on ventilator support at the time of the transplant had a 3-year survival rate of 52% compared to 73% for the other patients (p<0.0001). LUNG TRANSPLANT SURVIVAL: The 3-year survival rate for children (73%) appeared to be better than the adult rate (61%; p=0.8). Adult lung transplant survival was significantly worse in the case of a repeat lung transplant; a 3-year retransplant survival rate of 42% was obtained compared with 61% for first transplants (p=0.049). With respect to the underlying end-stage lung disease, no statistically significant difference in long-term survival could be detected in this cohort. The 3-year survival rates were: 62% for COPD/Emphysema, 70% for CF, 58% for IPF, 64% for Alpha-1 ATD and 56% for PPH (p=0.2). Our data demonstrated no effect of the recipient's age on long-term lung transplant survival, except for 2 senior patients in this cohort. At 3-years the survival rates for recipients aged 16-40, 41-55 and 56-65 were 65%, 60% and 62%, respectively (p=0.05). The 3-year survival rates for transplants performed with lungs from donors aged under 16, 16-44, 45-55 and over 55 was 57%, 64%, 55% and 62%, respectively (p=0.1) No association between the duration of cold ischemic time and 3-year survival was observed; under 3 hours, 3-4, 4-5, 5-6 and over 6 hours of ischemia resulted in 3-year survival rates of 53%, 59%, 64%, 68% and 57%, respectively (p=0.2). Early posttransplant outcome tended to be better for gender-matched transplants, while transplanting a female donor lung into a male recipient was associated with the worst prognosis. The 3-year survival rates were 65% for male/male, 63% for male/female, 48% for female/male and 61% for female/female (p=0.009). No effect of donor-to-recipient weight match was observed in this Eurotransplant cohort; when the donor-to-recipient weight ratio was below 0.8, the 3-year survival rate was 57%, compared with 59% for weight-matched pairs and 64% for patients who received a lung from an oversized donor (p=0.5). Long-term survival after lung transplantation was influenced by HLA matching. The 3-year survival rates were 100%, 68%, 70%, 65%, 54% and 55% for the HLA-A,-B,-DR 1, 2, 3, 4, 5 and 6 mismatched groups, respectively (p=0.06). A donor CMV+ and recipient CMV- match was a risk factor for long-term mortality, with 3-year survival rates of 56% for D+/R+, 55% for D+/R-, 71% for D-/R- and 62% for D-/R+ transplants (p=0.046). En-bloc transplantation of both lungs yielded worse early results, but the 3-year survival rates for patients who underwent single (60%), bilateral sequential double lung (63%) and en-bloc double lung transplantation (56%) were not different (p=0.2). Ventilator dependency was associated with a significantly reduced survival at 3 years. Patients on a ventilator support at the time of the transplant had a 3-year survival rate of 48% compared with 63% for other patients (p=0.006).