Waitlist Outcomes of Liver Transplant Candidates Who Were Reprioritized Under Share 35

Under Share 35, deceased donor (DD) livers are offered regionally to candidates with Model for End‐Stage Liver Disease (MELD) scores ≥35 before being offered locally to candidates with MELD scores <35. Using Scientific Registry of Transplant Recipients data from June 2013 to June 2015, we identified 1768 DD livers exported to regional candidates with MELD scores ≥35 who were transplanted at a median MELD score of 39 (interquartile range [IQR] 37–40) with 30‐day posttransplant survival of 96%. In total, 1764 (99.8%) exports had an ABO‐compatible candidate in the recovering organ procurement organization (OPO), representing 1219 unique reprioritized candidates who would have had priority over the regional candidate under pre–Share 35 allocation. Reprioritized candidates had a median waitlist MELD score of 31 (IQR 27–34) when the liver was exported. Overall, 291 (24%) reprioritized candidates had a comparable MELD score (within 3 points of the regional recipient), and 209 (72%) were eventually transplanted in 11 days (IQR 3–38 days) using a local (50%), regional (50%) or national (<1%) liver; 60 (21%) died, 13 (4.5%) remained on the waitlist and nine (3.1%) were removed for other reasons. Of those eventually transplanted, MELD score did not increase in 57%; it increased by 1–3 points in 37% and by ≥4 points in 5.7% after the export. In three cases, OPOs exchanged regional exports within a 24‐h window. The majority of comparable reprioritized candidates were not disadvantaged; however, 21% died after an export.     

Public attitudes toward contemporary issues in liver allocation

Allocation of scarce livers for transplantation seeks to balance competing ethical principles of autonomy, utility, and justice. Given the history and ongoing dependence of transplantation on public support for funding and organs, understanding and incorporating public attitudes into allocation decisions seems appropriate. In the context of the current controversy around liver allocation, we sought to determine public preferences about issues relevant to the debate. We performed multiple surveys of attitudes around donation and evaluated these using conjoint analysis and clarifying follow‐up questions. We found little public support that allocation decisions should be based solely on risk of waiting‐list mortality. Strong public sentiment supported maximizing outcomes after transplantation, prioritizing US citizens or residents, keeping organs local, and considering cost in allocation decisions. We then present a methodology for incorporating these preferences into the Model for End‐Stage Liver Disease (or MELD) priority score. Taken together, these findings suggest that current allocation schemes do not accurately reflect public preferences and suggest a framework to better align allocation with the values of the public.     

One Size Does Not Fit All—Regional Variation in the Impact of the Share 35 Liver Allocation Policy

Allocation policies for liver transplantation underwent significant changes in June 2013 with the introduction of Share 35. We aimed to examine the effect of Share 35 on regional variation in posttransplant outcomes. We examined two patient groups from the United Network for Organ Sharing dataset; a pre–Share 35 group composed of patients transplanted between June 17, 2012, and June 17, 2013 (n = 5523), and a post–Share group composed of patients transplanted between June 18, 2013, and June 18, 2014 (n = 5815). We used Kaplan–Meier and Cox multivariable analyses to compare survival. There were significant increases in allocation Model for End‐stage Liver Disease (MELD) scores, laboratory MELD scores, and proportions of patients in the intensive care unit and on mechanical, ventilated, or organ‐perfusion support at transplant post–Share 35. We also observed a significant increase in donor risk index in this group. We found no difference on a national level in survival between patients transplanted pre–Share 35 and post–Share 35 (p = 0.987). Regionally, however, posttransplantation survival was significantly worse in the post–Share 35 patients in regions 4 and 10 (p = 0.008 and p = 0.04), with no significant differences in the remaining regions. These results suggest that Share 35 has been associated with transplanting “sicker patients” with higher MELD scores, and although no difference in survival is observed on a national level, outcomes appear to be concerning in some regions.     

Trends and Patterns in Reporting of Patient Safety Situations in Transplantation

Analysis and dissemination of transplant patient safety data are essential to understanding key issues facing the transplant community and fostering a “culture of safety.” The Organ Procurement and Transplantation Network's (OPTN) Operations and Safety Committee de‐identified safety situations reported through several mechanisms, including the OPTN's online patient safety portal, through which the number of reported cases has risen sharply. From 2012 to 2013, 438 events were received through either the online portal or other reporting pathways, and about half were self‐reports. Communication breakdowns (22.8%) and testing issues (16.0%) were the most common types. Events included preventable errors that led to organ discard as well as near misses. Among events reported by Organ Procurement Organization (OPOs), half came from just 10 of the 58 institutions, while half of events reported by transplant centers came from just 21 of 250 institutions. Thirteen (23%) OPOs and 155 (62%) transplant centers reported no events, suggesting substantial underreporting of safety‐related errors to the national database. This is the first comprehensive, published report of the OPTN's safety efforts. Our goals are to raise awareness of safety data recently reported to the OPTN, encourage additional reporting, and spur systems improvements to mitigate future risk.     

Use of Population‐based Data to Demonstrate How Waitlist‐based Metrics Overestimate Geographic Disparities in Access to Liver Transplant Care

Liver allocation policies are evaluated by how they impact waitlisted patients, without considering broader outcomes for all patients with end‐stage liver disease (ESLD) not on the waitlist. We conducted a retrospective cohort study using two nationally representative databases: HealthCore (2006–2014) and five‐state Medicaid (California, Florida, New York, Ohio and Pennsylvania; 2002–2009). United Network for Organ Sharing (UNOS) linkages enabled ascertainment of waitlist‐ and transplant‐related outcomes. We included patients aged 18–75 with ESLD (decompensated cirrhosis or hepatocellular carcinoma) using validated International Classification of Diseases, Ninth Revision (ICD‐9)–based algorithms. Among 16 824 ESLD HealthCore patients, 3‐year incidences of waitlisting and transplantation were 15.8% (95% confidence interval [CI] : 15.0–16.6%) and 8.1% (7.5–8.8%), respectively. Among 67 706 ESLD Medicaid patients, 3‐year incidences of waitlisting and transplantation were 10.0% (9.7–10.4%) and 6.7% (6.5–7.0%), respectively. In HealthCore, the absolute ranges in states' waitlist mortality and transplant rates were larger than corresponding ranges among all ESLD patients (waitlist mortality: 13.6–38.5%, ESLD 3‐year mortality: 48.9–62.0%; waitlist transplant rates: 36.3–72.7%, ESLD transplant rates: 4.8–13.4%). States' waitlist mortality and ESLD population mortality were not positively correlated: ρ = ?0.06, p‐value = 0.83 (HealthCore); ρ = ?0.87, p‐value = 0.05 (Medicaid). Waitlist and ESLD transplant rates were weakly positively correlated in Medicaid (ρ = 0.36, p‐value = 0.55) but were positively correlated in HealthCore (ρ = 0.73, p‐value = 0.001). Compared to population‐based metrics, waitlist‐based metrics overestimate geographic disparities in access to liver transplantation.     

Nonstandard Exception Requests Impact Outcomes for Pediatric Liver Transplant Candidates

Nonstandard exceptions requests (NSERs), in which transplant centers appeal on a case‐by‐case basis for Pediatric End‐Stage Liver Disease/Mayo End‐Stage Liver Disease points, have been highly utilized for pediatric liver transplant candidates. We evaluated whether NSE outcomes are associated with waitlist and posttransplant mortality. United Network for Organ Sharing (UNOS) Scientific Registry of Transplant Recipients data on pediatric liver transplant candidates listed in 2009–2014 were analyzed after excluding those granted automatic UNOS exceptions. Of 2581 pediatric waitlist candidates, 44% had an NSE request. Of the 1134 children with NSERs, 93% were approved and 7% were denied. For children 2–18 years at listing, NSER denial increased the risk of waitlist mortality or removal for being too sick (subhazard ratio 2.99, 95% confidence interval [CI] 1.26–7.07, p = 0.01 in multivariate analysis). For children younger than 2 years, NSER denial did not impact waitlist mortality/removal. Children with NSER approved had reduced risk of graft loss 3 years posttransplant in univariate but not multivariable analysis (odds ratio 0.73, 95% CI 0.53–1.01, p = 06). Those with NSER denial had a higher risk of posttransplant death than those with no NSER (hazard ratio 2.43, 95% CI 0.99–5.95, p = 0.05, multivariable analysis), but NSER approval did not impact posttransplant death. Further research on NSER utilization in pediatric liver transplant is needed to optimize organ allocation and outcomes for children.     

Predictors of low risk for dropout from the liver transplant waiting list for hepatocellular carcinoma in long wait time regions: Implications for organ allocation

All patients with hepatocellular carcinoma meeting United Network for Organ Sharing T2 criteria currently receive the same listing priority for liver transplant (LT). A previous study from our center identified a subgroup with a very low risk of waitlist dropout who may not derive immediate LT benefit. To evaluate this issue at a national level, we analyzed within the United Network for Organ Sharing database 2052 patients with T2 hepatocellular carcinoma receiving priority listing from 2011 to 2014 in long wait time regions 1, 5, and 9. Probabilities of waitlist dropout were 18.3% at 1 year and 27% at 2 years. In multivariate analysis, factors associated with a lower risk of waitlist dropout included Model for End‐Stage Liver Disease‐Na < 15, Child's class A, single 2‐ to 3‐cm lesion, and α‐fetoprotein ≤20 ng/mL. The subgroup of 245 (11.9%) patients meeting these 4 criteria at LT listing had a 1‐year probability of dropout of 5.5% vs 20% for all others (P < .001). On explant, the low dropout risk group was more likely to have complete tumor necrosis (35.5% vs 24.9%, P = .01) and less likely to exceed Milan criteria (9.9% vs 17.7%, P = .03). We identified a subgroup with a low risk of waitlist dropout who should not receive the same LT listing priority.     

Justifying Nonstandard Exception Requests for Pediatric Liver Transplant Candidates: An Analysis of Narratives Submitted to the United Network for Organ Sharing, 2009–2014

Nonstandard exception requests (NSERs), for which transplant centers provide patient‐specific narratives to support a higher Model for End‐stage Liver Disease/Pediatric End‐stage Liver Disease score, are made for >30% of pediatric liver transplant candidates. We describe the justifications used in pediatric NSER narratives 2009–2014 and identify justifications associated with NSER denial, waitlist mortality, and transplant. Using United Network for Organ Sharing data, 1272 NSER narratives from 1138 children with NSERs were coded for analysis. The most common NSER justifications were failure‐to‐thrive (48%) and risk of death (40%); both associated with approval. Varices, involvement of another organ, impaired quality of life, and encephalopathy were justifications used more often in denied NSERs. Of the 25 most prevalent justifications, 60% were not associated with approval or denial. Waitlist mortality risk was increased when fluid overload or “posttransplant complication outside standard criteria” were cited and decreased when liver‐related infection was noted. Transplant probability was increased when the narrative mentioned liver‐related infections, and fluid overload for children <2 years old; it decreased when “posttransplant complications outside standard criteria” and primary sclerosing cholangitis were cited. This analysis provides novel insight and suggests targets for future consideration in outcomes research and exception criteria. Changes in the allocation system are needed to ensure equity and optimize outcomes for all pediatric candidates.     

Retransplantation outcomes for hepatitis C in the United States before and after direct-acting antiviral introduction

The success of direct-acting antiviral (DAA) therapy has led to near-universal cure for patients chronically infected with hepatitis C virus (HCV) and improved post–liver transplant (LT) outcomes. We investigated the trends and outcomes of retransplantation in HCV and non-HCV patients before and after the introduction of DAA. Adult patients who underwent re-LT were identified in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Multiorgan transplants and patients with >2 total LTs were excluded. Two eras were defined: pre-DAA (2009-2012) and post-DAA (2014-2017). A total of 2112 re-LT patients were eligible (HCV: n = 499 pre-DAA and n = 322 post-DAA; non-HCV: n = 547 pre-DAA and n = 744 post-DAA). HCV patients had both improved graft and patient survival after re-LT in the post-DAA era. One-year graft survival was 69.8% pre-DAA and 83.8% post-DAA (P < .001). One-year patient survival was 73.1% pre-DAA and 86.2% post-DAA (P < .001). Graft and patient survival was similar between eras for non-HCV patients. When adjusted, the post-DAA era represented an independent positive predictive factor for graft and patient survival (hazard ratio [HR]: 0.67; P = .005, and HR: 0.65; P = .004) only in HCV patients. The positive post-DAA era effect was observed only in HCV patients with first graft loss due to disease recurrence (HR: 0.31; P = .002, HR 0.32; P = .003, respectively). Among HCV patients, receiving a re-LT in the post-DAA era was associated with improved patient and graft survival.     

Impact of the Pediatric End‐Stage Liver Disease (PELD) growth failure thresholds on mortality among pediatric liver transplant candidates

The Pediatric End‐Stage Liver Disease (PELD) score is intended to determine priority for children awaiting liver transplantation. This study examines the impact of PELD's incorporation of “growth failure” as a threshold variable, defined as having weight or height <2 standard deviations below the age and gender norm (z‐score <2). First, we demonstrate the “growth failure gap” created by PELD's current calculation methods, in which children have z‐scores <2 but do not meet PELD's growth failure criteria and thus lose 6‐7 PELD points. Second, we utilized United Network for Organ Sharing (UNOS) data to investigate the impact of this “growth failure gap.” Among 3291 pediatric liver transplant candidates, 26% met PELD‐defined growth failure, and 17% fell in the growth failure gap. Children in the growth failure gap had a higher risk of waitlist mortality than those without growth failure (adjusted subhazard ratio [SHR] 1.78, 95% confidence interval [95% CI] 1.05‐3.02, P = .03). They also had a higher risk of posttransplant mortality (adjusted HR 1.55, 95% CI 1.03‐2.32, P = .03). For children without PELD exception points (n = 1291), waitlist mortality risk nearly tripled for those in the gap (SHR 2.89, 95% CI 1.39‐6.01, P = .005). Current methods for determining growth failure in PELD disadvantage candidates arbitrarily and increase their waitlist mortality risk. PELD should be revised to correct this disparity.     

A Share 21 model in liver transplantation: Impact on waitlist outcomes

With the introduction of Model for End‐Stage Liver Disease‐Sodium (MELD‐Na)–based allocation, the score at which patients benefit from liver transplantation (LT) has shifted from a score of 15 to 21. This study aimed to evaluate waitlist outcomes in patients with MELD‐Na scores <21 and explore the utility of replacing “Share 15” with “Share 21.” The study uses data from the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry. All adult patients registered for LT after implementation of the MELD‐Na–based allocation were evaluated. Waitlist patients with initial and final scores <21 were eligible. Patients with exception scores were excluded. To explore the potential impact of a Share 21 model, patients with an initial MELD‐Na score of 6‐14 (Group 1) and those with a score of 15‐20 (Group 2) were compared for waitlist outcomes. There were 3686 patients with an initial score of 6‐14 (Group 1) and 3282 with a score of 15‐20 (Group 2). Group 2, when compared to Group 1, showed comparable risk of mortality (adjusted hazard ratio [aHR] 1.00, P = .97), higher transplant probability (aHR 3.25, P < .001), and lower likelihood of removal from listing because of improvement (aHR 0.74, P = .011). Share 21 may enhance transplant opportunities and increase parity for patients with higher MELD‐Na scores without compromising waitlist outcomes.     

Frequency of whole‐organ in lieu of split‐liver transplantation over the last decade: Children experienced increased wait time and death

Organ shortage is a barrier to liver transplantation (LT). Split LT (SLT) increases organ utilization, saving 2 recipients. A simulation of Organ Procurement and Transplantation Network/United Network for Organ Sharing data (2007‐2017) was performed to identify whole‐organ LT grafts (WLT) that met the criteria for being splittable to 2 recipients. Waitlist consequences presented. Deceased donor (DD) livers transplanted as whole organs were evaluated for suitability to split. Of these DD organs, we identified the adolescent and adult recipients of WLT who were suitable for SLT. Pediatric candidates suitable to share the SLT were ascertained from DD match‐run lists, and 1342 splittable DD organs were identified; 438 WLT recipients met the criteria for accepting a SLT. Review of the 438 DD match‐run lists identified 420 children next on the list suitable for SLT. Three hundred thirty‐three children (79%) underwent LT, but had longer wait‐times compared to 591 actual pediatric SLT recipients (median 147 days vs 44 days, P  < 0.001). Thirty‐three of 420 children died on waitlist after a mean 206 days (standard deviation 317). Sharing organs suitable for splitting increases the number of LT, saving more lives. With careful patient selection, SLT will not be a disadvantage to the adult recipients. With a children‐first allocation scheme, SLT will naturally increase the number of allografts because adult organs are too large for small children.     

Outcomes of status 1 liver transplantation for Budd-Chiari Syndrome with fulminant hepatic failure

There is a paucity of data on the outcome of liver transplantation (LT) in Budd-Chiari Syndrome (BCS) patients who are listed as status 1. The objective of our study was to determine patient or graft survival following LT in status 1 BCS patients. We utilized United Network for Organ Sharing (UNOS) database to identify all adult patients (> 18 years of age) listed as status 1 with a primary diagnosis of BCS in the United States from 1998 to 2018, and analyzed their outcomes and compared it to non-status 1 BCS patients. Four hundred and forty-six patients with BCS underwent LT between 1998 and 2018, and of these 55 (12.3%) were listed as status 1. There was no difference in long-term post-liver transplant or “intention-to-treat” survival from the time of listing to death or the last day of follow-up between status 1 and non-status 1 groups. Graft and patient survival at 5 years for status 1 patients were 75% and 82%, respectively. Cox regression analysis showed that patients listed as status 1 (aHR: 0.45, p < .02) were associated with a better survival. BCS patients listed as status 1 have excellent survival following emergency LT.     

Functional status at listing predicts waitlist and posttransplant mortality in pediatric liver transplant candidates

Functional impairment is associated with mortality in adult liver transplant candidates. This has not been studied in pediatric liver transplant candidates. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to investigate functional status, waitlist mortality, and posttransplant outcomes in children younger than 18 years who were waitlisted in 2006‐2016 for primary liver transplant. Functional status was categorized, by using the Lansky Play‐Performance Scale (LPPS), as normal/good (80‐100), moderately impaired (50‐70), or severely impaired (10‐40) by center assessment. Among 3250 children not listed as Status 1A, 62% had an LPPS score of 80‐100, 25% had a score of 50‐70, and 13% had a score of 10‐40 at listing. Children with an LPPS score of 10‐40 at listing were more likely to die while on the waitlist (standardized hazard ratio 1.85, 95% confidence interval 1.09‐3.13, P = .02) in analyses adjusting for being on a ventilator, breathing support, or dialysis and other illness severity measures. For the 2565 children transplanted, an LPPS score of 10‐40 at listing drastically increased mortality risk by 1 year posttransplant (hazard ratio 5.77, 95% confidence interval 3.05‐10.91, P < .0005). LPPS scores of 10‐40 and 50‐70 both increased the risk of graft loss by 1 year. Functional status is an independent predictor of waitlist and posttransplant mortality in pediatric liver transplant candidates. Validated tools for the assessment of functional status in these children would improve our ability to predict mortality risk—and to appropriately prioritize them for transplant.     

Geographic disparities in donor lung supply and lung transplant waitlist outcomes: A cohort study

Despite the Final Rule mandate for equitable organ allocation in the United States, geographic disparities exist in donor lung allocation, with the majority of donor lungs being allocated locally to lower‐priority candidates. We conducted a retrospective cohort study of 19 622 lung transplant candidates waitlisted between 2006 and 2015. We used multivariable adjusted competing risk survival models to examine the relationship between local lung availability and waitlist outcomes. The primary outcome was a composite of death and removal from the waitlist for clinical deterioration. Waitlist candidates in the lowest quartile of local lung availability had an 84% increased risk of death or removal compared with candidates in the highest (subdistribution hazard ratio [SHR]: 1.84, 95% confidence interval [CI]: 1.51‐2.24, P < .001). The transplantation rate was 57% lower in the lowest quartile compared with the highest (SHR: 0.43, 95% CI: 0.39‐0.47). The adjusted death or removal rate decreased by 11% with a 50% increase in local lung availability (SHR: 0.89, 95% CI: 0.85‐0.93, P < .001) and the adjusted transplantation rate increased by 19% (SHR: 1.19, 95% CI: 1.17‐1.22, P < .001). There are geographically disparate waitlist outcomes in the current lung allocation system. Candidates listed in areas of low local lung availability have worse waitlist outcomes.