90-day Waitlist Mortality Research Articles

Effect of transjugular intrahepatic portosystemic shunt insertion on waitlist mortality and access to liver transplantation in budd-chiari syndrome.

The impact of transjugular intrahepatic portosystemic shunt (TIPS) on waitlist mortality and liver transplantation (LT) urgency in Budd-Chiari Syndrome (BCS) patients remains unclear. We analyzed BCS patients listed for LT in the UNOS database(2002-2024) to assess TIPS's impact on waitlist mortality and LT access via competing-risk analysis. We compared trends across two phases:Phase1(2002-2011) and Phase2(2012-2024). Of 815 BCS patients, 263(32.3%) received TIPS at listing. TIPS group had lower MELD-Na scores(20vs22,p<0.01), milder ascites(p=0.01), and fewer Status1 patients(those at risk of imminent death while awaiting LT)(2.7%vs8.3%,p<0.01) at listing compared to those without TIPS. TIPS patients had lower LT rates(43.3%vs56.5%,p<0.01) and longer waitlist times(350vs113d,p<0.01). TIPS use increased in Phase2(64.3%vs35.7%,p<0.01). Of 426 transplanted patients, 134(31.5%) received TIPS, showing lower MELD-Na scores(24vs27,p<0.01) and better medical conditions(Intensive care unit:14.9%vs21.9%,p<0.01) at LT. Status1 patients were fewer (3.7%vs12.3%,p<0.01), with longer waiting days(97vs26d,p<0.01) in TIPS group. TIPS use at listing increased from Phase1(25.6%) to Phase2(37.7%). From Phase1 to Phase2, ascites severity improved, re-LT cases decreased(Phase1:9.8%vsPhase2:2.2%,p<0.01), and cold ischemic time slightly decreased(Phase1:7.0vsPhase2:6.4 hours,p=0.14). Median donor body mass index significantly increased. No significant differences were identified in patient/graft survival at 1-/5-/10-year intervals between phases or TIPS/non-TIPS patients. While 90-day waitlist mortality showed no significant difference(p=0.11), TIPS trended towards lower mortality(subHazard ratio[sHR]:0.70[0.45-1.08]). Multivariable analysis indicated that TIPS was a significant factor in decreasing mortality(sHR:0.45[0.27-0.77],p<0.01). TIPS group also showed significantly lower LT access(sHR:0.65[0.53-0.81],p<0.01). Multivariable analysis showed that TIPS was a significant factor in decreasing access to LT(sHR:0.60[0.46-0.77],p<0.01). Sub-group analysis excluding Status1 or HCC showed similar trends. TIPS in BCS patients listed for LT reduces waitlist mortality and LT access, supporting its bridging role.

Revising model for end-stage liver disease from calendar-time cross-sections with correction for selection bias

BackgroundEurotransplant liver transplant candidates are prioritized by Model for End-stage Liver Disease (MELD), a 90-day waitlist survival risk score based on the INR, creatinine and bilirubin. Several studies revised the original MELD score, UNOS-MELD, with transplant candidate data by modelling 90-day waitlist mortality from waitlist registration, censoring patients at delisting or transplantation. This approach ignores biomarkers reported after registration, and ignores informative censoring by transplantation and delisting.MethodsWe study how MELD revision is affected by revision from calendar-time cross-sections and correction for informative censoring with inverse probability censoring weighting (IPCW). For this, we revised UNOS-MELD on patients with chronic liver cirrhosis on the Eurotransplant waitlist between 2007 and 2019 (n = 13,274) with Cox models with as endpoints 90-day survival (a) from registration and (b) from weekly drawn calendar-time cross-sections. We refer to the revised score from cross-section with IPCW as DynReMELD, and compare DynReMELD to UNOS-MELD and ReMELD, a prior revision of UNOS-MELD for Eurotransplant, in geographical validation.ResultsRevising MELD from calendar-time cross-sections leads to significantly different MELD coefficients. IPCW increases estimates of absolute 90-day waitlist mortality risks by approximately 10 percentage points. DynReMELD has improved discrimination over UNOS-MELD (delta c-index: 0.0040, p < 0.001) and ReMELD (delta c-index: 0.0015, p < 0.01), with differences comparable in magnitude to the addition of an extra biomarker to MELD (delta c-index: ± 0.0030).ConclusionCorrecting for selection bias by transplantation/delisting does not improve discrimination of revised MELD scores, but substantially increases estimated absolute 90-day mortality risks. Revision from cross-section uses waitlist data more efficiently, and improves discrimination compared to revision of MELD exclusively based on information available at listing.

Waitlist and posttransplant outcomes of pregnancy-related acute liver failure in the United States.

Data on the liver transplant (LT) outcomes of women with acute liver failure (ALF) due to liver diseases unique to pregnancy (P-ALF) are limited. Using United Network of Organ Sharing (UNOS) data (1987-2021), we analyzed waitlist and post-LT outcomes of ALF in women of childbearing age comparing P-ALF versus ALF due to liver diseases not unique to pregnancy. Baseline characteristics were compared between groups at the time of listing for LT. Of 3542 females aged 16-43 years and listed for LT for ALF, 84 (2%) listed for P-ALF were less likely to be Black (11 vs. 21%, p =0.033), have lower international normalized ratio (2.74 vs. 4.53 p <0.002), but more likely to have respiratory failure (56% vs. 41%, p <0.005), be on pressors (58% vs. 43%, p <0.005), and require dialysis (23% vs. 10%, p <0.001). The cumulative 90-day waitlist mortality (WLM) was lower in P-ALF vs. ALF due to liver diseases not unique to pregnancy (7.4 vs. 16.6%, p <0.001). Posttransplant survival rates at 5 years were similar (82% vs. 79%, p =0.89). In a Fine and Gray regression model controlled for listing year and Model for End-Stage Liver Disease score, 90-day WLM was lower in P-ALF with a sub-HR of 0.42 (95% CI: 0.19-0.94, p =0.035). Of 84 women with P-ALF and listed for LT, 45 listed for hemolysis-elevated liver enzymes-low platelets (HELLP) versus 39 for acute fatty liver of pregnancy had higher 90-day WLM (19.3% vs. 5.7% p <0.005). The 90-day WLM was about 10-fold higher in HELLP versus acute fatty liver of pregnancy with a sub-HR of 9.97 (95% CI: 1.64-60.55, p =0.013). In this UNOS database analysis of ALF among women of childbearing age, the waitlist outcome is better in women with P-ALF compared to women with ALF due to liver diseases not unique to pregnancy. Among women with P-ALF, the 90-day WLM is worse for HELLP versus acute fatty liver of pregnancy. Further studies are needed to improve the management of HELLP and prevent the development of ALF in this subgroup population.

The Effect of New Acuity Circle Policy on Simultaneous Liver and Kidney Transplantation in the United States

New deceased donor liver allocation policy using an acuity circle (AC)-based model was implemented on February 4th, 2020. The effect of AC policy on simultaneous liver-kidney transplantation (SLKT) remains unknown. The aim of this study was to assess the effect of AC policy on SLKT waitlist mortality, transplant probability, and post-transplant outcomes. Using the United Network for Organ Sharing database, 4908 adult SLKT candidates during two study periods, pre-AC (Aug-2017 to Feb-2020, N=2770) and post-AC (Feb-2020 to Dec-2021, N=2138) were analyzed. Outcomes included 90-day waitlist mortality, transplant probability, and post-transplant patient and graft survival. Compared to pre-AC period, SLKT recipients during post-AC period had higher median model for end-stage liver disease (MELD) score (24 vs 23, P<0.001), and less percentage of MELD exception (4.6% vs 7.7%, P=0.001). The 90-day waitlist mortality was same, but the probability of SLKT increased in post-AC period (P<0.001). Post-AC period also saw increased utilization of donation after cardiac death organs (11% vs 6.4%, P<0.001) and decreased rates of transplantation among Black candidates (7.9% vs 13%). After risk adjustment, post-AC period was not associated with any significant difference in 90-day waitlist mortality (sub-distribution hazard ratio [sHR] 0.80; 95% CI 0.56-1.16, P=0.24), and a higher 90-day probability of SLKT (sHR 1.68; 95% CI 1.41-1.99, P<0.001). During post-transplant period, one-year patient survival, liver and kidney graft survival were comparable between two study periods. The AC liver allocation policy was associated with increased transplant probability of adult SLKT candidates without decreasing waitlist mortality, post-transplant patient survival, or liver and kidney graft survival.

The effects of acuity circle policy on racial disparity in liver transplantation

BackgroundA new deceased donor liver allocation policy using an acuity circle–based model was implemented with the goal of providing equitable access to liver transplantation. We assessed the effect of the acuity circle policy on racial disparities in liver transplantation by analyzing waitlist mortality, transplant probability, and post-transplant outcomes. MethodsWe conducted a retrospective analysis of 23,717 adult liver transplantation candidates listed during the pre-acuity circle period and 21,051 during the post–acuity circle period (N = 44,768) in the United Network for Organ Sharing database from February 2020 to December 2021. ResultsAcuity circle–policy implementation was not associated with any significant difference in 90-day waitlist mortality but increased the 90-day probability of all candidates. Implementation did not decrease 90-day waitlist mortality but increased the 90-day transplant probability for all patients. One-year patient and liver graft survival were comparable between the study periods for all recipients, but Black recipients had higher rates of 1-year post–liver transplantation mortality and liver graft failure in both periods. ConclusionAlthough the implementation of the acuity circle policy is associated with an increase in transplant probability in White, Black, and Hispanic liver transplantation candidates, it did not change their waitlist mortality, nor did it lead to any improvement in the preexistent worse post-transplant outcomes in Black liver transplantation recipients.

MELD 3.0 for adolescent liver transplant candidates.

Adolescents constitute a unique waitlist cohort that is distinct from younger children. Model for End-stage Liver Disease (MELD) 3.0, which was developed in an adult population of liver transplant candidates, is planned to replace MELD-Sodium in the current liver allocation system for both adults and adolescents aged 12-17. We evaluated the predictive performance of MELD-Sodium, MELD 3.0, and Pediatric End-stage Liver Disease for 90-day waitlist mortality risk among adolescent liver transplant registrants. New waitlist registrations for primary liver transplants among individuals aged 12-17 and 18-25 for comparison were identified using Organ Procurement and Transplantation Network (OPTN) data from November 17, 2004, to December 31, 2021. The predictive performance of the current and proposed MELD and Pediatric End-stage Liver Disease scores was assessed using Harrell's concordance ( c ) statistic. There were 1238 eligible listings for adolescents aged 12-17 and 1740 young adults aged 18-25. In the adolescent group, 90-day survival was 97.8%, compared with 95.9% in those aged 18-25 (log-rank p = 0.005), with no significant differences when stratified by sex or indication. Among adolescents, increasing MELD 3.0 was associated with an increased hazard of mortality (HR=1.27, 95% CI: 1.18-1.37), and the c -statistic for 90-day waitlist survival using MELD 3.0 was 0.893 compared with 0.871 using MELD-Sodium and 0.852 using Pediatric End-stage Liver Disease. The discriminative ability of MELD 3.0 to rank adolescents according to the risk of death within 90 days was robust. Although MELD 3.0 was initially developed and validated in adults, MELD 3.0 may also improve the prediction of waitlist mortality in adolescents and better represent their urgency for liver transplants.

Model for end-stage liver disease underestimates mortality of patients with acute-on-chronic liver failure waiting for liver transplantation.

Patients with acute-on-chronic liver failure (ACLF) show excess mortality in MELD-Na based organ allocation for liver transplantation (LT). Whether MELD-based allocation in the Eurotransplant region similarly underprioritizes ACLF patients is unknown. 428 patients listed for LT from 01/2010 to 02/2021 at a tertiary center in Germany were screened and 209 patients included as derivation (n=123) and validation cohort (n=86). Competing risk analysis for waitlist mortality and LT as competing events was performed. 90-day waitlist mortality for patients with MELD < and ≥ 25 at baseline was 9% vs. 33%, respectively (p=0.009). Competing risk analysis shows significantly higher 90-day waitlist mortality in patients listed with ACLF compared to those without ACLF (p=0.021) in the low MELD stratum. Probability of LT was similar between the two groups (p=0.91). In the high MELD group, 90-day waitlist mortality and rates of LT were not significantly different between patients with and without ACLF (31% vs. 20%, p=0.55 and 59% vs. 60%, p=0.72, respectively). Post-transplant survival was similar between patients with and without ACLF. This result was confirmed in the validation cohort. MELD-based organ allocation in the Eurotransplant region underestimates waitlist mortality in patients with ACLF in lower MELD ranges.

Impact of the acuity circle model for liver allocation on multivisceral transplant candidates

Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018-2020) and post-AC (2020-2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96-74.05; p=.054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15-0.75; p=.008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p=.04) and pediatric recipients (65% to 15%; p=.002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.

Extreme hyponatremia as a risk factor for early mortality after liver transplantation in the MELD-sodium era.

The impact of hyponatremia on waitlist and post-transplant outcomes following the implementation of MELD-Na-based liver allocation remains unclear. We investigated waitlist and postliver transplant (LT) outcomes in patients with hyponatremia before and after implementing MELD-Na-based allocation. Adult patients registered for a primary LT between 2009 and 2021 were identified in the OPTN/UNOS database. Two eras were defined; pre-MELD-Na and post-MELD-Na. Extreme hyponatremia was defined as a serum sodium concentration ≤120mEq/l. Ninety-day waitlist outcomes and post-LT survival were compared using Fine-Gray proportional hazard and mixed-effects Cox proportional hazard models. A total of 118487 patients were eligible (n=64940: pre-MELD-Na; n=53547: post-MELD-Na). In the pre-MELD-Na era, extreme hyponatremia at listing was associated with an increased risk of 90-day waitlist mortality ([ref: 135-145] HR: 3.80; 95% CI: 2.97-4.87; P<0.001) and higher transplant probability (HR: 1.67; 95% CI: 1.38-2.01; P<0.001). In the post-MELD-Na era, patients with extreme hyponatremia had a proportionally lower relative risk of waitlist mortality (HR: 2.27; 95% CI 1.60-3.23; P<0.001) and proportionally higher transplant probability (HR: 2.12; 95% CI 1.76-2.55; P<0.001) as patients with normal serum sodium levels (135-145). Extreme hyponatremia was associated with a higher risk of 90, 180, and 365-day post-LT survival compared to patients with normal serum sodium levels. With the introduction of MELD-Na-based allocation, waitlist outcomes have improved in patients with extreme hyponatremia but they continue to have worse short-term post-LT survival.

Paradigm Change in Liver Transplantation Practice After the Implementation of the Liver-Kidney Allocation Policy.

The Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) policy regarding kidney allocation for liver transplantation (LT) patients was implemented in August 2017. This study evaluated the effects of the simultaneous liver-kidney transplantation (SLKT) policy on outcomes in LT alone (LTA) patients with kidney dysfunction. We analyzed adult primary LTA patients with kidney dysfunction at listing (estimated glomerular filtration rate [eGFR] less than 30mL/minute or dialysis requirement) between January 2015 and March 2019 using the OPTN/UNOS registry. Waitlist practice and kidney transplantation (KT) listing after LTA were compared between prepolicy and postpolicy groups. There were 3821 LTA listings with eGFR<30mL/minute included. The daily number of listings on dialysis was significantly higher in Era 2 (postpolicy group) than Era 1 (prepolicy group) (1.21/day versus 0.95/day; P<0.001). Of these LTA listings, 90-day LT waitlist mortality, LTA probability, and 1-year post-LTA survival were similar between eras. LTA recipients in Era 2 had a higher probability for KT listing after LTA than those in Era 1 (6.2% versus 3.9%; odds ratio[OR],3.30; P<0.001), especially those on dialysis (8.4% versus 2.0%; OR, 4.38; P<0.001). Under the safety net rule, there was a higher KT probability after LTA (26.7% and 53% at 6months in Eras 1 and 2, respectively; P=0.02). After the implementation of the policy, the number of LTA listings among patients on dialysis increased significantly. While their posttransplant survival did not change, KT listing after LTA increased. The safety net rule led to high KT probability and a low waitlist mortality rate in patients who were listed for KT after LTA. These results suggest that the policy successfully achieved the goals of providing appropriate opportunities of KT for LT patients, which did not compromise LTA waitlist or posttransplant outcomes in patients with kidney dysfunction and provided KT opportunities if patients developed kidney failure after LTA.

Disease-specific waitlist outcomes in liver transplantation - a retrospective study.

This study aimed to evaluate possible discrepancies in waitlist outcomes between liver diseases, including alcohol-related liver disease (ALD), nonalcoholic steatohepatitis (NASH), hepatitis C virus infection (HCV), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). Patients registered for liver transplantation from January 11, 2016, to June 30, 2018, were evaluated using OPTN/UNOS registry. Waitlist outcomes were compared between the five-disease groups. Patients were categorized by initial MELD-Na-score (6-20, 21-29, and ≥30) to identify outcome variations. Prognostic impact of transplantation was assessed according to final MELD-Na scores using Cox regression analysis modeling transplantation as a time-dependent covariate. 6053 with ALD, 3814 with NASH, 1558 with HCV, 602 with PBC, and 819 with PSC were eligible. Compared to ALD with comparable MELD-Na-scores, NASH with lower [adjusted hazard ratio (aHR)=1.30, P=0.042] and mid-scores (aHR=1.35, P=0.008) showed significantly higher risk of 1-year waitlist mortality, and PBC with higher scores showed significantly higher risk of 90-day (aHR=1.69, P=0.03) and 1-year waitlist mortality (aHR=1.69, P=0.02). Positive prognostic impact of transplantation was not seen until score of 24-27 in ALD, 18-20 in HCV, 15-17 in NASH, and 24-27 in PBC and PSC. There are significant differences in waitlist outcomes among etiologies, which may differ the optimal transplant timing.

Validating a novel score based on interaction between ACLF grade and MELD score to predict waitlist mortality

Among candidates listed for liver transplant (LT), the model for end-stage liver disease (MELD) score may not capture acute-on-chronic liver failure (ACLF) severity. Data on the interaction between ACLF and MELD score in predicting waitlist mortality are scarce. We analyzed the UNOS database (01/2002 to 06/2018) for LT listings in adults with cirrhosis and ACLF (without hepatocellular carcinoma). ACLF grades 1, 2, 3a, and 3b- were defined using the modified EASL-CLIF criteria. Of 18,416 candidates with ACLF at listing (mean age 54 years, 69% males, 63% Caucasians), 90-day waitlist mortality (patient death or being too sick for LT) was 21.6% (18%, 20%, 25%, and 39% for ACLF grades 1, 2, 3a, and 3b, respectively). Using a Fine and Gray regression model, we identified an interaction between MELD and ACLF grade, with ACLF having a higher impact at lower MELD scores. Other variables included candidate's age, sex, liver disease etiology, listing MELD, ACLF grade, obesity, and performance status. A score developed using parameter estimates from the interaction model on the derivation cohort (n = 9,181) stratified the validation cohort (n= 9,235) into quartiles: Q1 (score <10.42), Q2 (10.42-12.81), Q3 (12.82-15.50), and Q4 (>15.50). Waitlist mortality increased with each quartile from 13%, 18%, 23%, and 36%, respectively. Observed vs. expected waitlist mortality deciles in the validation cohort showed good calibration (goodness of fit p= 0.98) and correlation (R= 0.99). Among selected candidates who have ACLF at listing, MELD score and ACLF interact in predicting cumulative risk of 90-day waitlist mortality, with higher impact of ACLF grade at lower listing MELD score. Validating these findings in large prospective studies will support consideration of both MELD and ACLF when prioritizing transplant candidates and allocating liver grafts. In patients with cirrhosis listed for liver transplantation, the presence of multiorgan failure, a condition referred to as acute-on-chronic liver failure, is associated with high waiting list mortality rates. Current organ allocation policy disadvantages patients with this condition. This study describes and validates a new scoring method that performs better than the currently available scoring systems. Further validation of this approach may reduce the deaths of patients with cirrhosis and acute-on-chronic liver failure on the transplant waiting list.

Patients with severe acute-on-chronic liver failure are disadvantaged by model for end-stage liver disease-based organ allocation policy.

Mortality for patients with acute-on-chronic liver failure (ACLF) may be underestimated by the model for end-stage liver disease-sodium (MELD-Na) score. To assess waitlist outcomes across varying grades of ACLF among a cohort of patients listed with a MELD-Na score ≥35, and therefore having similar priority for liver transplantation. We analysed the United Network for Organ Sharing (UNOS) database, years 2010-2017. Waitlist outcomes were evaluated using Fine and Gray's competing risks regression. We identified 6342 candidates at listing with a MELD-Na score ≥35, of whom 3122 had ACLF-3. Extra-hepatic organ failures were present primarily in patients with four to six organ failures. Competing risks regression revealed that candidates listed with ACLF-3 had a significantly higher risk for 90-day waitlist mortality (Sub-hazard ratio (SHR)=1.41; 95% confidence interval [CI] 1.12-1.78) relative to patients with lower ACLF grades. Subgroup analysis of ACLF-3 revealed that both the presence of three organ failures (SHR=1.40, 95% CI 1.20-1.63) or four to six organ failures at listing (SHR=3.01; 95% CI 2.54-3.58) was associated with increased waitlist mortality. Candidates with four to six organ failures also had the lowest likelihood of receiving liver transplantation (SHR=0.61, 95% CI 0.54-0.68). The Share 35 rule was associated with reduced 90-day waitlist mortality among the full cohort of patients listed with ACLF-3 and MELD-Na score ≥35 (SHR=0.59; 95% CI 0.49-0.70). However, Share 35 rule implementation was not associated with reduced waitlist mortality among patients with four to six organ failures (SHR=0.76; 95% CI 0.58-1.02). The MELD-Na score disadvantages patients with ACLF-3, both with and without extra-hepatic organ failures. Incorporation of organ failures into allocation policy warrants further exploration.

Liver transplantation after share 35: Impact on pretransplant and posttransplant costs and mortality.

Share 35 was implemented in 2013 to direct livers to the most urgent candidates by prioritizing Model for End-Stage Liver Disease (MELD) ≥ 35 patients. We aim to evaluate this policy's impact on costs and mortality. Our study includes 834 wait-listed patients and 338 patients who received deceased donor, solitary liver transplants at Mayo Clinic between January 2010 and December 2014. Of these patients, 101 (30%) underwent transplantation after Share 35. After Share 35, 29 (28.7%) MELD ≥ 35 patients received transplants, as opposed to 46 (19.4%) in the pre-Share 35 era (P = 0.06). No significant difference in 90-day wait-list mortality (P = 0.29) nor 365-day posttransplant mortality (P = 0.68) was found between patients transplanted before or after Share 35. Mean costs were $3,049 (P = 0.30), $5226 (P = 0.18), and $10,826 (P = 0.03) lower post-Share 35 for the 30-, 90-, and 365-day pretransplant periods, and mean costs were $5010 (P = 0.41) and $5859 (P = 0.57) higher, and $9145 (P = 0.54) lower post-Share 35 for the 30-, 90-, and 365-day posttransplant periods. In conclusion, the added cost of transplanting more MELD ≥ 35 patients may be offset by pretransplant care cost reduction. Despite shifting organs to critically ill patients, Share 35 has not impacted mortality significantly. Liver Transplantation 23:11-18 2017 AASLD.

Outcomes of Multiple Listing for Adult Heart Transplantation in the United States: Analysis of OPTN Data From 2000 to 2013

ObjectivesThis study sought to assess the association of multiple listing with waitlist outcomes and post–heart transplant (HT) survival. BackgroundHT candidates in the United States may register at multiple centers. Not all candidates have the resources and mobility needed for multiple listing; thus this policy may advantage wealthier and less sick patients. MethodsWe identified 33,928 adult candidates for a first single-organ HT between January 1, 2000 and December 31, 2013 in the Organ Procurement and Transplantation Network database. ResultsWe identified 679 multiple-listed (ML) candidates (2.0%) who were younger (median age, 53 years [interquartile range (IQR): 43 to 60 years] vs. 55 years [IQR: 45 to 61 years]; p < 0.0001), more often white (76.4% vs. 70.7%; p = 0.0010) and privately insured (65.5% vs. 56.3%; p < 0.0001), and lived in zip codes with higher median incomes (US$90,153 [IQR: US$25,471 to US$253,831] vs. US$68,986 [IQR: US$19,471 to US$219,702]; p = 0.0015). Likelihood of ML increased with the primary center’s median waiting time. ML candidates had lower initial priority (39.0% 1A or 1B vs. 55.1%; p < 0.0001) and predicted 90-day waitlist mortality (2.9% [IQR: 2.3% to 4.7%] vs. 3.6% [IQR: 2.3% to 6.0]%; p < 0.0001), but were frequently upgraded at secondary centers (58.2% 1A/1B; p < 0.0001 vs. ML primary listing). ML candidates had a higher HT rate (74.4% vs. 70.2%; p = 0.0196) and lower waitlist mortality (8.1% vs. 12.2%; p = 0.0011). Compared with a propensity-matched cohort, the relative ML HT rate was 3.02 (95% confidence interval: 2.59 to 3.52; p < 0.0001). There were no post-HT survival differences. ConclusionsMultiple listing is a rational response to organ shortage but may advantage patients with the means to participate rather than the most medically needy. The multiple-listing policy should be overturned.

Update on the management of the liver transplant patient.

To review and highlight recent literature regarding the medical management of adult patients undergoing liver transplantation. The addition of serum sodium concentration to the model for end-stage liver disease (MELD) score more accurately predicts 90-day waitlist mortality. Predictors of waitlist mortality and posttransplant survival include lower albumin and the presence of ascites, varices, and encephalopathy, as well as more nontraditional predictors such as older age, obesity, frailty, and sarcopenia. Indications for liver transplantation are evolving with the advent of effective therapy for hepatitis C and the increased prevalence of nonalcoholic steatohepatitis. Disparities persist in the current allocation system, including geographic variation and MELD inflation for hepatocellular carcinoma. Share 35 allows for broader regional sharing of organs for patients with the highest need, without detrimental effects on waitlist mortality or survival. Everolimus is a recently approved option for posttransplant immunosuppression that spares renal function. The MELD score has enabled the liver transplant community to equitably allocate organs. Recent literature has focused on the limitations of the MELD score and the disparities inherent in the current system. The next steps for liver transplantation will be to develop strategies to further optimize waitlist prioritization and organ allocation.

Hepatic encephalopathy is associated with significantly increased mortality among patients awaiting liver transplantation.

The prioritization of liver transplantation (LT) for patients with end-stage liver disease uses the Model for End-Stage Liver Disease (MELD), which attempts to identify the sickest patients and thereby those who are in greatest need for LT. Hepatic encephalopathy (HE) is not included in MELD, and severity of liver disease and risk of wait-list removal or wait-list death may be underestimated by MELD in patients with HE. Using United Network for Organ Sharing registry data, we evaluated the impact of HE on 90-day wait-list survival among adult LT wait-list registrants in the United States from 2003 to 2012. Survival was stratified by HE severity (none, grade 1-2, grade 3-4) and MELD. There were 84,947 new LT wait-list registrants during the study period; 36.8% had no HE, 57.4% had grade 1-2 HE, and 5.9% had grade 3-4 HE. Ninety-day wait-list mortality was significantly higher among patients with grade 3-4 HE compared with patients with grade 1-2 HE or no HE (24.4% versus 6.8% versus 3.5%; P < 0.001). When stratified by MELD, patients with grade 3-4 HE had 90-day wait-list mortality similar to that of nonencephalopathic patients with MELD scores 6-7 points higher. With the multivariate Cox proportional hazards model, patients with grade 3-4 HE had 66% greater risk of 90-day mortality than patients without HE (hazard ratio = 1.66, 95% CI = 1.45-1.90; P < 0.001). The inclusion of HE severity in MELD improved the area under receiver operating curve for predicting 90-day wait-list survival from 0.6508 to 0.6863. In conclusion, grade 3-4 HE at time of wait-list registration significantly increases 90-day wait-list mortality independent of MELD score. Incorporating HE in the assessment of LT priority may improve prognostication of liver disease severity and prioritization for LT.

Risk Stratification and Transplant Benefit in Children Listed for Heart Transplant in the United States

The sickest children among those listed for heart transplant (HT) are also at higher risk of post-transplant mortality. We hypothesized that transplant benefit, defined as percentage reduction in risk of 1-year mortality on receiving HT, increases with higher risk of wait-list mortality. We analyzed all children aged <18 years listed for first HT in the United States between July 2004 and December 2010. We developed a model for 90-day wait-list mortality (or removal because of deterioration) and stratified listed children into deciles based on their risk of wait-list mortality. Listed children were followed up for 1 year to assess cumulative 1-year wait-list mortality among the 10 risk groups. We developed a model for 1-year post-transplant mortality to estimate the risk of post-transplant mortality for children in each risk group. Of 2979 listed children, 15% reached the wait-list end point within 90 days and 18% within 1 year. Of 2034 HT recipients, 6.8% died within 90 days and 10.8% within 1 year. The risk of 90-day wait-list mortality increased progressively from 2.4% to 51.6% from the first to the tenth risk decile. Transplant benefit increased progressively across the wait-list risk groups (P<0.001 for trend). However, transplant benefit for children in the top 5% of risk (7.4%) was lower than that for children in the 91st to 95th percentile of risk (10.3%). Sicker children on the wait-list benefit more from HT unless the post-transplant mortality is predicted to be very high. Whether consideration of transplant benefit in allocation policy can improve overall survival among listed children requires further analysis.

Moderate ascites identifies patients with low model for end-stage liver disease scores awaiting liver transplantation who have a high mortality risk

Donor livers are offered to patients with the highest risk of death. How ascites could inform risk models to reduce liver transplant wait-list mortality is unclear. All adult candidates for primary liver transplantation for cirrhosis without exception points who were registered with the Organ Procurement and Transplantation Network from 2005 to 2007 composed our study cohort. Using Cox models and advanced discriminative metrics and paying attention to geographic disparities, we evaluated the additional risk discrimination of moderate ascites over that of the Model for End-Stage Liver Disease (MELD) or the Model for End-Stage Liver Disease plus serum sodium (MELD-Na) alone for the prediction of 90-day wait-list mortality. Additional analyses examined lower mortality risk candidates and those listed in high-demand, low-supply United Network for Organ Sharing regions in which accounting for ascites may most significantly affect wait-list mortality. Between 2005 and 2007, 18,124 subjects were listed for liver transplantation. Mortality was higher in patients with moderate ascites (15.4% versus 6.0%, P < 0.0001), and this risk persisted despite adjustments for MELD (hazard ratio = 1.58, 95% confidence interval = 1.42-1.76) and MELD-Na (hazard ratio = 1.42, 95% confidence interval = 1.28-1.58). The effect of moderate ascites was more prominent with a MELD score <21 (equal to 4.7 MELD units) or with a MELD-Na score <21 (equal to 3.5 MELD-Na units). Wait-list mortality was higher in patients with moderate ascites who were listed in high-demand, limited-supply regions (25.8% versus 17.5% at 1 year, P < 0.01). With the addition of moderate ascites, there was improvement in the overall risk model, particularly with a MELD score <21, as measured by the C index and integrated discrimination improvement. Moderate ascites informed risk prediction, particularly with a MELD score <21 and in high-demand, limited-supply regions. Under the MELD system, the presence of moderate ascites should prompt clinicians to consider strategies to expand access to transplantation, such as the use of extended donor liver grafts.

The Model for End-Stage Liver Disease Accurately Predicts 90-Day Liver Transplant Wait-List Mortality in Atlantic Canada

To determine the generalizability of the predictions for 90-day mortality generated by Model for End-stage Liver Disease (MELD) and the serum sodium augmented MELD (MELDNa) to Atlantic Canadian adults with end-stage liver disease awaiting liver transplantation (LT). The predictive accuracy of the MELD and the MELDNa was evaluated by measurement of the discrimination and calibration of the respective models' estimates for the occurrence of 90-day mortality in a consecutive cohort of LT candidates accrued over a five-year period. Accuracy of discrimination was measured by the area under the ROC curves. Calibration accuracy was evaluated by comparing the observed and model-estimated incidences of 90-day wait-list failure for the total cohort and within quantiles of risk. The area under the ROC curve for the MELD was 0.887 (95% CI 0.705 to 0.978) - consistent with very good accuracy of discrimination. The area under the ROC curve for the MELDNa was 0.848 (95% CI 0.681 to 0.965). The observed incidence of 90-day wait-list mortality in the validation cohort was 7.9%, which was not significantly different from the MELD estimate of 6.6% (95% CI 4.9% to 8.4%; P=0.177) or the MELDNa estimate of 5.8% (95% CI 3.5% to 8.0%; P=0.065). Global goodness-of-fit testing found no evidence of significant lack of fit for either model (Hosmer-Lemeshow c2 [df=3] for MELD 2.941, P=0.401; for MELDNa 2.895, P=0.414). Both the MELD and the MELDNa accurately predicted the occurrence of 90-day wait-list mortality in the study cohort and, therefore, are generalizable to Atlantic Canadians with end-stage liver disease awaiting LT.