Post-transplant Survival Research Articles

(65) - History of Donor Drug Use and Post-Transplant Survival in Pediatric Heart Transplant Recipients: A Propensity Score Matched Analysis

(65) - History of Donor Drug Use and Post-Transplant Survival in Pediatric Heart Transplant Recipients: A Propensity Score Matched Analysis

(324) - Association of Center Volume with Post-Transplant Survival After the 2018 US Heart Allocation Policy Change

(324) - Association of Center Volume with Post-Transplant Survival After the 2018 US Heart Allocation Policy Change

(95) - Impact of Ex Vivo Machine Perfusion on Post-Transplant Survival in Extended Criteria Hearts Donated After Brain Death

(95) - Impact of Ex Vivo Machine Perfusion on Post-Transplant Survival in Extended Criteria Hearts Donated After Brain Death

(311) - Contextual Effects of Donor Lung Factors on Post-Transplant Survival

(311) - Contextual Effects of Donor Lung Factors on Post-Transplant Survival

(143) - Incorporating Donor Variables Improves Accuracy of One-Year Post-Transplant Survival Prediction for Adult Heart Transplant Recipients

(143) - Incorporating Donor Variables Improves Accuracy of One-Year Post-Transplant Survival Prediction for Adult Heart Transplant Recipients

(114) - Socioeconomic Deprivation Predicts Worse Post-Transplant Survival in US Pediatric Heart Transplantation

(114) - Socioeconomic Deprivation Predicts Worse Post-Transplant Survival in US Pediatric Heart Transplantation

(443) - Worse Risk-Adjusted Post-Transplant Survival for Women in the New Heart Transplant Allocation System

(443) - Worse Risk-Adjusted Post-Transplant Survival for Women in the New Heart Transplant Allocation System

Can we safely expand the donation after circulatory death donor heart pool by extending the donor age limit?

ObjectiveThis study evaluates the impact of donor age on outcomes following donation after circulatory death heart transplantation. MethodsThe United Network for Organ Sharing registry was queried to analyze adult recipients who underwent isolated donation after circulatory heart transplantation from January 1, 2019, to September 30, 2023. The cohort was stratified into 2 groups according to donor age, where advanced donor age was defined as 40 years or more. Outcomes were 90-day and 1-year post-transplant survival. Propensity score matching was performed. Subgroup analysis was performed to evaluate the effects of recipient age on 90-day survival among the recipients with advanced-age donors. ResultsA total of 994 recipients were included in the study period, and 161 patients (17.1%) received allografts from advanced-age donors. During the study period, the annual incidence of donation after circulatory heart transplantation with advanced-age donors substantially increased. The recipients with advanced-age donors had similar 90-day and 1-year post-transplant survivals compared with the recipients with younger donors. The comparable 90-day survival persisted in a propensity score–matched comparison. In the subgroup analysis among the recipients with advanced-age donors, the recipients aged 60 years or more had significantly reduced 90-day survival compared with the recipients aged less than 60 years. ConclusionsThe use of appropriately selected donation after circulatory donors aged 40 years or more has similar survival compared with that of younger donors. With careful candidate risk stratification and selection, consideration of using donation after circulatory donors aged more than 40 years may further ameliorate ongoing organ shortage with comparable early post-transplant outcomes.

(774) - Impact of Early Graft Dysfunction on Conditional 1-Year Post-Transplant Survival: A French National Cohort Study

(774) - Impact of Early Graft Dysfunction on Conditional 1-Year Post-Transplant Survival: A French National Cohort Study

The future of liver transplantation.

Over the last 50 years, liver transplantation has evolved into a procedure routinely performed in many countries worldwide. Those able to access this therapy frequently experience a miraculous risk-benefit ratio, particularly if they face the imminently life-threatening disease. Over the decades, the success of liver transplantation, with dramatic improvements in early posttransplant survival, has aggressively driven demand. However, despite the emergence of living donors to augment deceased donors as a source of organs, supply has lagged far behind demand. As a result, rationing has been an unfortunate focus in recent decades. Recent shifts in the epidemiology of liver disease combined with transformative innovations in liver preservation suggest that the underlying premise of organ shortage may erode in the foreseeable future. The focus will sharpen on improving equitable access while mitigating constraints related to workforce training, infrastructure for organ recovery and rehabilitation, and their associated costs. Research efforts in liver preservation will undoubtedly blossom with the aim of optimizing both the timing and conditions of transplantation. Coupled with advances in genetic engineering, regenerative biology, and cellular therapies, the portfolio of innovation, both broad and deep, offers the promise that, in the future, liver transplantation will not only be broadly available to those in need but also represent a highly durable life-saving therapy.

Patient Selection for Living Donor Liver Transplantation in Acute-on-chronic Liver Failure

Background and objectivesAcute-on-chronic liver failure (ACLF) is associated with high short-term mortality without liver transplantation (LT). Selection criteria for LT in these patients are not well defined. The objective of this study was to determine factors associated with post-transplant survival in ACLF. MethodsThis was a single center retrospective study of patients who underwent living donor liver transplantation (LDLT) for ACLF between 2012 and 2022. Out of 1093 transplants, 110 patients had underlying ACLF, based on the European Association for the Study of the Liver-Chronic Liver Failure Consortium (EASL-CLIF) criteria. We looked at factors associated with 1-year post-transplant survival. ResultsThe median (IQR) MELD score was 33.5(31-38) and the 1-year post-transplant survival was 72%. Six risk factors were associated with post-transplant survival, namely, body mass index >30 Kg/m2 [HR, 4.4; 95% CI,1.8-10.7], platelet count <66000/μl [HR, 2.91; CI,1.2-6.6], poor response to medical treatment [HR, 2.6; CI, 1.1-5.7], drug-resistant bacterial or fungal cultures [HR, 4.2; CI, 1.4-12.4], serum creatinine >2.5 mg/dl [HR, 3.4; CI, 1.5-7.7 ], and graft-to-recipient weight ratio < 0.7 [HR, 4.8; CI, 1.4-16.3]. The 1-year post-transplant survival was 84% in patients with 0-2 risk factors (n=89) and was 6% with 3 risk factors (n=15) (P<0.001). For 1-year post-transplant survival, the area under curve (AUC) for the current model was 0.8 (0.69-0.9). The AUC for CLIF-ACLF, CLIF-SOFA, and EASL-CLIF ACLF grade was < 0.5. ConclusionIn LT for ACLF, acceptable survival can be achieved when less than three high risk factors are present.

Outcomes following concomitant multiorgan heart transplantation from circulatory death donors: The United States experience

BackgroundDonation after circulatory death (DCD) has reemerged as a method of expanding the donor heart pool. Given the high waitlist mortality of multiorgan heart candidates, we evaluated waitlist outcomes associated with willingness to consider DCD offers and post-transplant outcomes following DCD transplant for these candidates. MethodsUsing the United Network for Organ Sharing database, we identified adult multiorgan heart candidates and recipients between 1/1/2020 and 3/31/2023. Among candidates that met inclusion criteria, we compared the cumulative incidence of transplant, with waitlist death/deterioration as a competing risk, by willingness to consider DCD offers. Among recipients of DCD vs. brain death (DBD) transplants, we compared perioperative outcomes and post-transplant survival. ResultsOf 1,802 heart-kidney, 266 heart-liver, and 440 heart-lung candidates, 15.8%, 12.4% and 31.1%, respectively, were willing to consider DCD offers. On adjusted analysis, willingness to consider DCD offers was associated with higher likelihood of transplant for all multiorgan heart candidates and decreased likelihood of waitlist deterioration for heart-lung candidates. Of 1,100 heart-kidney, 173 heart-liver, and 159 heart-lung recipients, 5.4%, 2.3%, and 2.5%, respectively, received DCD organs. Recipients of DCD and DBD heart-kidney transplants had similar likelihood of perioperative outcomes and 1-year survival. All other DCD multiorgan heart recipients have survived to last follow-up. ConclusionsMultiorgan heart candidates who were willing to consider DCD offers had favorable waitlist outcomes, and heart-kidney recipients of DCD transplants had similar post-transplant outcomes to recipients of DBD transplants. We recommend the use of DCD organs to increase the donor pool for these high-risk candidates.

Validation of a novel donor lung scoring system based on the updated lung Composite Allocation Score

Lung transplantation (LTx) continues to have lower rates of long-term graft survival compared with other organs. Additionally, lung utilization rates from brain-dead donors remain substantially lower compared with other solid organs, despite a growing need for LTx and the significant risk of waitlist mortality. This study aims to examine the effects of using a combination of the recently described novel lung donor (LUNDON) acceptability score and the newly adopted recipient lung Composite Allocation Score (CAS) to guide transplantation. We performed a review of nearly 18 000 adult primary lung transplants from 2015-2022 across the US with retroactive calculations of the CAS value. The medium-CAS group (29.6-34.5) had superior 1-year posttransplant survival. Importantly, the combination of high-CAS (> 34.5) recipients with low LUNDON score (≤ 40) donors had the worst survival at 1 year compared with any other combination. Additionally, we constructed a model that predicts 1-year and 3-year survival using the LUNDON acceptability score and CAS values. These results suggest that caution should be exercised when using marginally acceptable donor lungs in high-priority recipients. The use of the LUNDON score with CAS value can potentially guide clinical decision-making for optimal donor-recipient matches for LTx.

Transplant benefit-based offering of deceased donor livers in the United Kingdom

The National Liver Offering Scheme (NLOS) was introduced in the UK in 2018 to offer livers from deceased donors to patients on the national waiting list based, for most patients, on calculated transplant benefit. Before NLOS, livers were offered to transplant centres by geographic donor zones and, within centres, by estimated recipient need for a transplant. UK Transplant Registry data on patient registrations and transplants were analysed to build statistical models for survival on the list (M1) and survival post-transplantation (M2). A separate cohort of registrations - not seen by the models before - was analysed to simulate what liver allocation would have been under M1, M2 and a transplant benefit score (TBS) model (combining both M1 and M2), and to compare these allocations to what had been recorded in the UK Transplant Registry. The number of deaths on the waiting list and patient life years were used to compare the different simulation scenarios and to select the optimal allocation model. Registry data were monitored, pre- and post-NLOS, to understand the performance of the scheme. The TBS was identified as the optimal model to offer donation after brain death (DBD) livers to adult and large paediatric elective recipients. In the first 2 years of NLOS, 68% of DBD livers were offered using the TBS to this type of recipient. Monitoring data indicate that mortality on the waiting list post-NLOS significantly decreased compared with pre-NLOS (p <0.0001), and that patient survival post-listing was significantly greater post- compared to pre-NLOS (p= 0.005). In the first two years of NLOS offering, waiting list mortality fell while post-transplant survival was not negatively impacted, delivering on the scheme's objectives. The National Liver Offering Scheme (NLOS) was introduced in the UK in 2018 to increase transparency of the deceased donor liver offering process, maximise the overall survival of the waiting list population, and improve equity of access to liver transplantation. To our knowledge, it is the first scheme that offers organs based on statistical prediction of transplant benefit: the transplant benefit score. The results are important to the transplant community - from healthcare practitioners to patients - and demonstrate that, in the first two years of NLOS offering, waiting list mortality fell while post-transplant survival was not negatively impacted, thus delivering on the scheme's objectives. The scheme continues to be monitored to ensure that the transplant benefit score remains up-to-date and that signals that suggest the possible disadvantage of some patients are investigated.

Creating synthetic populations in transplantation: A Bayesian approach enabling simulation without registry re-sampling.

Computer simulation has played a pivotal role in analyzing alternative organ allocation strategies in transplantation. The current approach to producing cohorts of organ donors and candidates for individual-level simulation requires directly re-sampling retrospective data from a transplant registry. This historical data may reflect outmoded policies and practices as well as systemic inequities in candidate listing, limiting contemporary applicability of simulation results. We describe the development of an alternative approach for generating synthetic donors and candidates using hierarchical Bayesian network probability models. We developed two Bayesian networks to model dependencies among 10 donor and 36 candidate characteristics relevant to waitlist survival, donor-candidate matching, and post-transplant survival. We estimated parameters for each model using Scientific Registry of Transplant Recipients (SRTR) data. For 100 donor and 100 candidate synthetic populations generated, proportions for each categorical donor or candidate attribute, respectively, fell within one percentage point of observed values; the interquartile ranges (IQRs) of each continuous variable contained the corresponding SRTR observed median. Comparisons of synthetic to observed stratified distributions demonstrated the ability of the method to capture complex joint variability among multiple characteristics. We also demonstrated how changing two upstream population parameters can exert cascading effects on multiple relevant clinical variables in a synthetic population. Generating synthetic donor and candidate populations in transplant simulation may help overcome critical limitations related to the re-sampling of historical data, allowing developers and decision makers to customize the parameters of these populations to reflect realistic or hypothetical future states.

The Treatment of Refractory Vitiligo With Autologous Cultured Epithelium Grafting: A Real-World Retrospective Cohort Study.

Surgical intervention is the main therapy for refractory vitiligo. We developed a modified autologous cultured epithelial grafting (ACEG) technique for vitiligo treatment. Between January 2015 and June 2019, a total of 726 patients with vitiligo underwent ACEG in China, with patient characteristics and clinical factors being meticulously documented. Using a generalized linear mixed model, we were able to assess the association between these characteristics and the repigmentation rate. ACEG demonstrated a total efficacy rate of 82.81% (1754/2118) in treating 726 patients, with a higher repigmentation rate of 64.87% compared to conventional surgery at 52.69%. Notably, ACEG showed a better response in treating segmental vitiligo, lesions on lower limbs, age ≤ 18, and stable period > 3 years. A keratinocyte:melanocyte ratio below 25 was found to be advantageous too. Single-cell RNA sequencing analysis revealed an increase in melanocyte count and 2 subclusters of keratinocytes after ACEG, which remained higher in repigmented sites even after 1 year. ACEG is a promising therapy for refractory vitiligo. Patient age, clinical type, lesion site, and stability before surgery influence repigmentation in ACEG. The mechanism of repigmentation after ACEG treatment is likely not confined to the restoration of melanocyte populations. It may also involve an increase in the number of keratinocytes that support melanocyte function within the affected area. These keratinocytes may aid the post-transplant survival and function of melanocytes by secreting cytokines and extracellular matrix components. registered with Chictr.org.cn (ChiCTR2100051405).

Primary liver transplantation vs transplant after Kasai portoenterostomy in children with biliary atresia: A retrospective Brazilian single-center cohort.

Biliary atresia (BA) is the most common indication for pediatric liver trans plantation, although portoenterostomy is usually performed first. However, due to the high failure rate of portoenterostomy, liver transplantation has been advocated as the primary procedure for patients with BA. It is still unclear if a previous portoenterostomy has a negative impact on liver transplantation outcomes. To investigate the effect of prior portoenterostomy in infants un dergoing liver transplantation for BA. This was a retrospective cohort study of 42 pediatric patients with BA who underwent primary liver transplantation from 2013 to 2023 at a single tertiary center in Brazil. Patients with BA were divided into two groups: Those under going primary liver transplantation without portoenterostomy and those undergoing liver transplantation with prior portoenterostomy. Continuous variables were compared using the Student's t-test or the Kruskal-Wallis test, and categorical variables were compared using the χ2 or Fisher's exact test, as appropriate. Multivariable Cox regression analysis was performed to determine risk factors for portal vein thrombosis. Patient and graft survival analyses were conducted with the Kaplan-Meier product-limit estimator, and patient subgroups were compared using the two-sided log-rank test. Forty-two patients were included in the study (25 [60%] girls), 23 undergoing liver transplantation without prior portoenterostomy, and 19 undergoing liver transplantation with prior portoenterostomy. Patients with prior portoenterostomy were older (12 vs 8 months; P = 0.02) at the time of liver transplantation and had lower Pediatric End-Stage Liver Disease scores (13.2 vs 21.4; P = 0.01). The majority of the patients (35/42, 83%) underwent living-donor liver transplantation. The group of patients without prior portoenterostomy appeared to have a higher incidence of portal vein thrombosis (39 vs 11%), but this result did not reach statistical significance. Prior portoenterostomy was not a protective factor against portal vein thrombosis in the multivariable analysis after adjusting for age at liver transplantation, graft-to-recipient weight ratio, and use of vascular grafts. Finally, the groups did not significantly differ in terms of post-transplant survival. In our study, prior portoenterostomy did not significantly affect the outcomes of liver transplantation.

Management of alcohol-associated liver disease and alcohol use disorder in liver transplant candidates and recipients: Challenges and opportunities.

Alcohol-associated liver disease poses a significant global health burden, with rising alcohol consumption and prevalence of alcohol use disorder (AUD) contributing to increased morbidity and mortality. This review examines the challenges and opportunities in the care of candidates and recipients of liver transplant (LT) with AUD. Despite advancements in posttransplant patient survival, the risk of disease recurrence and alcohol relapse remains substantial. Several challenges have been identified, including (1) rising disease burden of alcohol-associated liver disease, variable transplant practices, and systemic barriers; (2) disparities in mental health therapy access and the impact on transplant; (3) variable definitions, underdiagnosis, and stigma affecting access to care; and (4) post-LT relapse, its risk factors, and consequential harm. The review focuses on the opportunities to improve AUD care for candidates and recipients of LT through effective biochemical monitoring, behavioral and pharmacologic approaches, creating Centers of Excellence for post-LT AUD care, advocating for policy reforms, and ensuring insurance coverage for necessary services as essential steps toward improving patient outcomes. The review also highlights unmet needs, such as the scarcity of addiction specialists, and calls for further research on personalized behavioral treatments, digital health, and value-based care models to optimize AUD care in the LT setting.

Age Matters: What Affects the Cumulative Lifespan of a Transplanted Liver?

Assess factors affecting the cumulative lifespan of a transplanted liver. Liver ageing is different from other solid organs. It is unknown how old a liver can actually get after liver transplantation (LT). Deceased donor liver transplants from 1988-2021 were queried from the United States (US) UNOS registry. Cumulative liver age was calculated as donor age + recipient graft survival. In total, 184,515 livers were included. Most were DBD-donors (n=175,343). The percentage of livers achieving >70, 80, 90 and 100years cumulative age was 7.8% (n=14,392), 1.9% (n=3,576), 0.3% (n=528), and 0.01% (n=21), respectively. The youngest donor age contributing to a cumulative liver age >90years was 59years, with post-transplant survival of 34years. In pediatric recipients, 736 (4.4%) and 282 livers (1.7%) survived >50 and 60years overall, respectively. Transplanted livers achieved cumulative age >90years in 2.86-per-1000 and >100years in 0.1-per-1000. The US population at-large has a cumulative "liver age" >90years in 5.35-per-1000 persons, and >100y in 0.2-per-1000. Livers aged>60 years at transplant experienced both improved cumulative survival ( P <0.0001) and interestingly improved survival after transplantation ( P <0.0001). Recipient warm-ischemia-time of >30minutes was most predictive of reduced cumulative liver survival overall (n=184,515, HR=1.126, P <0.001) and excluding patients with mortality in the first 6month (n=151,884, HR=0.973, P <0.001). In summary, transplanted livers frequently get as old as those in the average population despite ischemic-reperfusion-injury and immunosuppression. The presented results justify using older donor livers regardless of donation type, even in sicker recipients with limited options.

Adult-to-adult right lobe graft living donor liver transplantation for acute-on-chronic liver failure: a single-centre retrospective study in Vietnam.

Acute-on-chronic liver failure (ACLF) has a high mortality rate, and liver transplantation is considered a definite treatment for patients with this condition. This study aims to evaluate the outcomes of living donor liver transplantation (LDLT) in ACLF patients in a single centre in a lower middle-income country, Vietnam. This was a retrospective study at the 108 Military Central Hospital (Hanoi, Vietnam), enroling 51 patients diagnosed with ACLF based on Asian Pacific Association for the Study of the Liver (APASL) criteria who underwent LDLT with a right lobe graft from December 2019 to December 2022. The authors utilize the model for end-stage liver disease (MELD) and APASL ACLF Research Consortium (AARC) scores to evaluate and stratify the severity of ACLF. The average age of all patients was 47.27±13.61, with 88.24% being male. The average BMI was 22.78±2.61. The most common underlying liver disease was chronic viral hepatitis B (88.2%). The average MELD score of the patients was 34.90±5.61, with 33.3% having MELD score greater than or equal to 40. In terms of ACLF severity, five patients (9.8%) had grade I ACLF, 35 patients (68.6%) had grade II ACLF, and 11 patients (21.6%) had grade III ACLF. The average AARC score was 9.43±1.68. The duration of treatment in the ICU was 8.59±7.27 days, and the length of hospital stay was 28.02±13.45 days. The most common post-transplant complication was biliary complication (19.61%). Death occurred in 7 patients (13.7%). The survival rates at 6 months, 1 year, and 3 years were 84%, 81.7%, and 81.7%, respectively. Living donor liver transplantation for ACLF patients is safe and has a high post-transplant survival rate. Multidisciplinary care before, during, and after surgery, and the decision to do a liver transplant early, is essential in saving the lives of ACLF patients.