An Update on Usage of High-Risk Donors in Liver Transplantation

The ideal management for end stage liver disease, acute liver failure, and hepatocellular carcinoma (HCC), within specific criteria, is liver transplantation (LT). Over the years, there has been a steady increase in the candidates listed for LT, without a corresponding increase in the donor pool. Therefore, due to organ shortage, it has been substantially difficult to reduce waitlist mortality among patients awaiting LT. Thus, marginal donors such as elderly donors, steatotic donors, split liver, and donors after cardiac death (DCD), which were once not commonly used, are now considered. Furthermore, it is encouraging to see the passing of Acts, such as the HIV Organ Policy Equity (HOPE) Act, enabling further research and development in utilizing HIV grafts. Subsequently, the newer antivirals have aided in successful post-transplant period, especially for hepatitis C positive grafts. However, currently, there is no standardization, and protocols are center specific in the usage of marginal donors. Therefore, studies with longer follow ups are required to standardize its use.

Transplant Centers That Measure Frailty as Part of Clinical Practice Have Better Outcomes

Frailty predicts adverse outcomes for kidney transplant (KT) patients; yet the impact of clinical assessments of frailty on center-level outcomes remains unclear. We sought to test whether KT centers that measure frailty as part of clinical practice have better pre- and post-KT outcomes. We conducted a survey of US transplant centers (11/2017-4/2018), 132 KT centers (response rate=65.3%) reported frequencies of frailty assessment at candidacy evaluation and KT admission. Center characteristics and clinical outcomes were gleaned from the national registry (2017-2019). Poisson regression was used to estimate incidence rate ratios (IRRs) of waitlist mortality rate and transplantation rate in candidates and graft loss rates in recipients by frequency of frailty assessment. All models were adjusted for case mix and center characteristics. Given similar center characteristics, centers assessing frailty at evaluation had a lower waitlist mortality rate (always=3.5, sometimes=3.2, never=4.1 deaths per 100 person-years). After adjustment, centers assessing frailty at evaluation had a lower rates of waitlist mortality (always IRR=0.91, 95% CI:0.84-0.99; sometimes=0.89, 95% CI:0.83-0.96) and transplantation (always IRR=0.94, 95% CI:0.91-0.97; sometimes=0.88, 95% CI:0.85-0.90) than those never assessing frailty. Centers that always assessed frailty at KT admission had 0.71 (95% CI:0.54-0.92) times the rate of death-censored graft loss than their counterparts never assessing frailty. Assessing frailty at evaluation is associated with lower transplantation rate but better waitlist survival; centers always assessing frailty at admission are likely to have better graft survival. Research is needed to explore how routine assessment of frailty in other clinical practices benefits broader patient populations.

Waiting time and mortality rate on lung transplant candidates in Japan: a single-center retrospective cohort study

Background As lung transplantation (LTX) is a valuable treatment procedure for end-stage pulmonary disease, delayed referral to a transplant center should be avoided. We aimed to conduct a single-center analysis of the survival time after listing for LTX and waitlist mortality in each disease category in a Japanese population. Methods We included patients listed for LTX at Tohoku University Hospital from January 2007 to December 2020 who were followed up until March 2021. Pulmonary disease was categorized into the Obstructive, Vascular, Suppurative, Fibrosis, and Allogeneic groups. Risk factors for waitlist mortality were assessed using a Cox proportional hazards model. The Kaplan–Meier method was used to model time to death. Results We included 269 LTX candidates. Of those, 100, 72, and 97 patients were transplanted, waiting, and dead, respectively. The median time to LTX and time to death were 796 days (interquartile range [IQR] 579–1056) and 323 days (IQR 129–528), respectively. The Fibrosis group showed the highest mortality (50.9%; p < .001), followed by the Allogeneic (35.0%), Suppurative (33.3%), Vascular (32.1%), and Obstructive (13.1%) groups. The Fibrosis group showed a remarkable risk for waitlist mortality (hazard ratio 3.32, 95% CI 2.11–4.85). Conclusions In Japan, the waiting time is extremely long and candidates with Fibrosis have high mortality. There is a need to document outcomes based on the underlying disease for listed LTX candidates to help determine the optimal timing for listing patients based on the estimated local waiting time.

Inactive status is an independent predictor of liver transplant waitlist mortality and is associated with a transplant centers median meld at transplant

Background Approximately 30% of patients on the liver transplant waitlist experience at least one inactive status change which makes them temporarily ineligible to receive a deceased donor transplant. We hypothesized that inactive status would be associated with higher mortality which may differ on a transplant centers’ or donor service areas’ (DSA) Median MELD at Transplant (MMaT). Methods Multi-state models were constructed (OPTN database;06/18/2013-06/08/2018) using DSA-level and transplant center-level data where MMaT were numerically ranked and categorized into tertiles. Hazards ratios were calculated between DSA and transplant center tertiles, stratified by MELD score, to determine differences in inactive to active transition probabilities. Results 7,625 (30.2% of sample registrants;25,216 total) experienced at least one inactive status change in the DSA-level cohort and 7,623 experienced at least one inactive status change in the transplant-center level cohort (30.2% of sample registrants;25,211 total). Inactive patients with MELD≤34 had a higher probability of becoming re-activated if they were waitlisted in a low or medium MMaT transplant center or DSA. Transplant rates were higher and lower re-activation probability was associated with higher mortality for the MELD 26–34 group in the high MMaT tertile. There were no significant differences in re-activation, transplant probability, or waitlist mortality for inactivated patients with MELD≥35 regardless of a DSA’s or center’s MMaT. Conclusion This study shows that an inactive status change is independently associated with waitlist mortality. This association differs by a centers’ and a DSAs’ MMaT. Prioritization through care coordination to resolve issues of inactivity is fundamental to improving access.

Long-Term Outcomes and Prognosticators of Pediatric Primary Dilated Cardiomyopathy in an Asian Cohort

Background: Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy. The epidemiological profiles and prognosticators of clinical outcomes in Asian populations are not well elucidated.Methods: Data of 104 children aged &lt;18 years with a diagnosis of primary DCM from January 1990 to December 2019 in our institutional database were retrospectively investigated. Relevant demographic, echocardiographic, and clinical variables were recorded for analysis. A P &lt;0.05 was considered statistically significant.Results: The median age at diagnosis was 1.4 years (interquartile range = 0.3–9.1 years), and 52.9% were males. During a median follow-up duration of 4.8 years, 48 patients (46.2%) were placed on the transplantation waitlist, and 52.1% of them eventually received heart transplants. An exceptionally high overall waitlist mortality rate was noted (27.1%), which was even higher (43.5%) if the diagnostic age was &lt;3 years. The 1-, 5-, and 10-year transplant-free were 61.1, 48.0, and 42.8%. Age at diagnosis &gt;3 years and severe mitral regurgitation at initial diagnosis were independent risk factors for death or transplantation (hazard ratios = 2.93 and 3.31, respectively; for both, P &lt;0.001). In total, 11 patients (10.6%) experienced ventricular function recovery after a median follow-up of 2.5 (interquartile range = 1.65–5) years. Younger age at diagnosis was associated a higher probability of ventricular function recovery.Conclusions: Despite donor shortage for heart transplantation and subsequently high waitlist mortality, our data from an Asian cohort indicated that transplant-free long-term survival was comparable with that noted in reports from Western populations. Although younger patients had exceptionally higher waitlist mortality, lower diagnostic age was associated with better long-term survival and higher likelihood of ventricular function recovery.

Short and long term outcomes of cardiac amyloidosis patients listed for heart transplantation in the united states: a propensity-matched analysis

Background Heart transplantation (HT) in cardiac amyloidosis (CA) patients has been historically controversial due to the risk of amyloid recurrence. However, recent single-center experiences suggest good outcomes in carefully selected patients. We sought to evaluate contemporary outcomes of CA patients listed for HT in the U.S. and evaluate predictors of survival Methods Using data from the United Network for Organ Sharing database on adult patients listed for a donor heart in the U.S. between 2010 and 2019, we identified 3 cohorts of patients, namely CA, dilated cardiomyopathy (DCM), and non-CA restrictive cardiomyopathy (RCM). Propensity-match analysis was used to compare primary outcomes of waitlist mortality and post-transplant graft survival between CA and DCM. Results Over the study period, 411 CA patients (mean age 62.7 years, 16.1% female) were added to the waitlist. In the propensity-matched cohorts, the rates of waitlist mortality were 33.7, 15.8, and 15.6 per 100 person-years for CA, DCM, and non-CA RCM, respectively. Compared to DCM, there was significantly higher waitlist mortality for CA (HR=1.75, 95% CI=1.16–2.65). Over the study period, 330 CA patients were transplanted with donor hearts. The 1-year graft survival rates for CA, DCM, and non-CA RCM were 89%, 92%, and 86%, respectively; and 5-year graft survival rates were 78%, 82%, and 76%, respectively. Graft survival for CA was significantly worse than DCM (HR=1.46, 1.03–2.08), and the two most significant risk factors for poor graft survival among CA patients were renal failure requiring dialysis while on the waitlist (HR=5.4, 1.6–17) and prior history of malignancy (HR=1.7, 1.0–29). CA patients with neither of the risk factor had 1- and 5-year graft survival that is comparable to those of DCM (HR=1.18, 0.81–1.74). On the other hand, CA patients with either of the risk factor had 1- and 5-year graft survival of 81% and 65%, respectively, (HR=2.33, 1.40–3.87, compared to DCM). Conclusion CA patients experience higher waitlist mortality and worse post-transplant graft survival compared to DCM. However, we identified two risk factors that can be used for further risk-stratification in these patients to achieve comparable graft survival as DCM. FUNDunding Acknowledgement Type of funding sources: None.

Outcomes of diabetic patients with end-stage heart failure listed for heart transplantation: a propensity-matched analysis

Background There are on-going concerns about offering heart transplants to patients with diabetes due to the risk of poor outcomes. We investigated the current trends and outcomes of patients listed for heart transplants in the U.S. and provided a method for risk-stratification. Methods Using data from the United Network for Organ Sharing (UNOS), we identified heart failure patients listed for heart transplants between 2010 and 2019. Diabetic patients were propensity-matched with non-diabetes, and waitlist mortality as well as post-transplant graft survival were compared between the two matched groups. Further risk-stratification of the diabetic cohort was done based on the risk factors that independently predict the risk of graft failure. Results 28,928 adult patients (30% diabetic) with end-stage heart failure were added to the waitlist over the study period. In the propensity-matched cohort, waitlist mortality was higher with diabetics compared to non-diabetics: 19.3 vs 17.1 deaths per 100 person-years, respectively, (HR=1.13 (95% CI=1.04–1.22, p=0.002). Over the study period, 5739 diabetics (mean age 57.6 years, 21.9% female) were transplanted. A total of 1308 (23.3%) and 1143 (20.4%) graft failures occurred in diabetic and non-diabetic recipients, respectively. Compared to non-diabetics, diabetics experienced worse graft survival (HR=1.17, 95% CI=1.08–1.26, p&lt;0.001). We developed a risk score based on the 12 risk factors/markers that independently predict worse graft survival and a risk score of 4 reasonably differentiates between low and high-risk diabetics. Low risk diabetics (score≤4) had similar graft survival as non-diabetics with 1- and 5-year survival of 92.7% and 80.5%, respectively, (HR=0.91, 95% CI=0.82–1.01, p=0.06). On the other hand, high-risk diabetics had worse graft survival compared to non-diabetics (HR=1.52, 95% CI=1.38–1.67, P&lt;0.001) with 1- and 5-year graft survival of 86.8% and 69.8%, respectively. Conclusion Diabetic patients with end-stage heart failure listed for heart transplantation experience higher waitlist mortality and worse post-transplant graft survival compared to non-diabetics. However, a simple risk score can be used for further risk-stratification in these patients to maximize survival benefit. FUNDunding Acknowledgement Type of funding sources: None.