OPTN/SRTR 2022 Annual Data Report: Intestine.

Intestine remains the least frequently transplanted solid organ, although the survival and quality-of-life benefits of transplant to individuals with irreversible intestinal failure have been well demonstrated. The trend seen over the past 15 years of fewer listings and fewer transplants appears to be continuing, most noticeably in infants, children, and adolescents. There were only 146 additions to the intestine waiting list in 2022, and the proportion of adult candidates continues to increase, so that now 61% of the intestine waiting list are adult candidates. There has been little change in the distribution by sex, race and ethnicity, or primary diagnosis on the waiting list, or for those receiving transplant. The transplant rate for adults has decreased to 55.6 transplants per 100 patient-years, but the pediatric transplant rate remains relatively stable at 22.8 transplants per 100 patient-years. The decrease in transplant rates for adults is primarily the result of falling rates for those listed for combined intestine-liver, and this is reflected in the pretransplant mortality rates, which are twice as high for candidates in need of both organs compared with those listed for intestine alone. Overall, intestine transplant numbers decreased to a total of 82 intestine transplants in 2022, only one above the lowest ever value of 81 in 2019. No major changes were seen in the immunosuppression protocols, with most recipients having induction therapy and tacrolimus-based maintenance. Graft failure rates appear to have improved at 1, 3, and 5 years for intestine without liver, but this is not seen for combined intestine-liver. Graft and patient survival are better for pediatric recipients compared with adult recipients for both liver-inclusive and liver-exclusive transplant. Rates of posttransplant lymphoproliferative disorder are higher for recipients of intestine without liver.

Adjusting for race in metrics of organ procurement organization performance.

The Scientific Registry of Transplant Recipients has previously reported the effects of adjusting for demographic variables, including race, in the Centers for Medicare & Medicaid Services (CMS) organ procurement organization (OPO) performance metrics: donation rate and transplant rate. CMS chose not to adjust for most demographic variables other than age (for the transplant rate), arguing that there is no biological reason that these variables would affect the organ donation/utilization decision. However, organ donation is a process based on altruism and trust, not a simple biological phenomenon. Focusing only on biological impacts on health ignores other pathways through which demographic factors can influence OPO outcomes. In this study, we update analyses of demographic adjustment on the OPO metrics for 2020 with a specific focus on adjusting for race. We find that adjusting for race would lead to 8 OPOs changing their CMS tier rankings, including 2 OPOs that actually overperform the national rate among non-White donors improving from a tier 3 ranking (facing decertification without possibility of recompeting) to a tier 2 ranking (allowing the possibility of recompeting). Incorporation of stratified and risk-adjusted metrics in public reporting of OPO performance could help OPOs identify areas for improvement within specific demographic categories.

Impact of Centers for Medicare and Medicaid Services Final Rule on Organ Procurement Organization Metrics and Procedural Trends in the Procurement of Pancreata for Research.

OBJECTIVE: Pancreata recovered for research are included as a success (or positive) in the Centers for Medicare and Medicaid Services' (CMS) donation and organ transplantation rate metrics for recertification of organ procurement organizations (OPOs). MATERIALS AND METHODS: Given these metrics directly incentivize recovery of pancreata for research, this study tracks trends in recovery of pancreata for research across the implementation of the CMS metrics. RESULTS: In the 26 months before the December 2, 2020, publication of the CMS metrics, research pancreata as a percent of organs transplanted, including research pancreata, was 1.7% nationally, including as much as 10.8% of organs transplanted within any OPO. In the 26 months after the CMS metrics were published, research pancreata increased to 5.1% of organs counted as transplants nationally, including as much as 20.3% within any OPO. If research pancreata were excluded from the CMS metrics, 6 OPOs would change their CMS evaluation status for recertification purposes: 2 would move up a tier and 4 would move down a tier. CONCLUSIONS: Procurement of research pancreata has increased since the publication of the CMS performance metrics, OPOs vary in their recovery of pancreata for research, and recovery of pancreata for research can affect recertification of OPOs.

OPTN/SRTR 2021 Annual Data Report: Intestine.

There has been just over 30 years of experience in clinical intestine transplant. A rise in demand until 2007 with improving transplant outcomes preceded a subsequent fall in demand due, at least in part, to improvements in pretransplant care of patients with intestinal failure. Over the past 10 to 12 years, there has been no suggestion of an increase in demand and, particularly for adult transplant, there may be a continued trend toward fewer additions to the waiting list and fewer transplants, especially in those needing combined intestine-liver transplant. In addition, over the same period there has been no noticeable improvement in graft survival, with 1- and 5-year graft failure rates averaging 21.6% and 52.5%, respectively, for intestine-alone transplants and 28.6% and 47.2%, respectively, for combined intestine-liver allografts.

Removing geographic boundaries from liver allocation: A method for designing continuous distribution scores.

BACKGROUND: The Organ Procurement and Transplantation Network (OPTN) is eliminating geographic boundaries in liver allocation, in favor of continuous distribution. Continuous distribution allocates organs via a composite allocation score (CAS): a weighted sum of attributes like medical urgency, candidate biology, and placement efficiency. The opportunity this change represents, to include new variables and features for prioritizing candidates, will require lengthy and contentious discussions to establish community consensus. Continuous distribution could instead be implemented rapidly by computationally translating the allocation priorities for pediatric, status 1, and O/B blood type liver candidates that are presently implemented via geographic boundaries into points and weights in a CAS. METHODS: Using simulation with optimization, we designed a CAS that is minimally disruptive to existing prioritizations, and that eliminates geographic boundaries and minimizes waitlist deaths without harming vulnerable populations. RESULTS: Compared with Acuity Circles (AC) in a 3-year simulation, our optimized CAS decreased deaths from 7771.2 to 7678.8 while decreasing average (272.66 NM vs. 264.30 NM) and median (201.14 NM vs. 186.49 NM) travel distances. Our CAS increased travel only for high MELD and status 1 candidates (423.24 NM vs. 298.74 NM), and reduced travel for other candidates (198.98 NM vs. 250.09 NM); overall travel burden decreased. CONCLUSION: Our CAS reduced waitlist deaths by sending livers for high-MELD and status 1 candidates farther, while keeping livers for lower MELD candidates nearby. This advanced computational method can be applied again after wider discussions of adding new priorities conclude; our method designs score weightings to achieve any specified feasible allocation outcomes.

Fully nonparametric survival analysis in the presence of time-dependent covariates and dependent censoring.

In the presence of informative right censoring and time-dependent covariates, we estimate the survival function in a fully nonparametric fashion. We introduce a novel method for incorporating multiple observations per subject when estimating the survival function at different covariate values and compare several competing methods via simulation. The proposed method is applied to survival data from people awaiting liver transplant.

Time to discard the term "discard".

The 2022 Scientific Registry of Transplant Recipients Consensus Conference "People Driven Transplant Metrics" offered an opportunity for a diverse group of stakeholders in the solid organ transplant community to exchange ideas about what information and metrics are important to different stakeholders. Participating patients and family members called on the transplant community to cease using the term "discards" to refer to donated organs that are not transplanted.

Logistical burden of offers and allocation inefficiency in circle-based liver allocation.

Recent changes to liver allocation replaced donor service areas with circles as the geographic unit of allocation. Circle-based allocation might increase the number of transplantation centers and candidates required to place a liver, thereby increasing the logistical burden of making and responding to offers on organ procurement organizations and transplantation centers. Circle-based allocation might also increase distribution time and cold ischemia time (CIT), particularly in densely populated areas of the country, thereby decreasing allocation efficiency. Using Scientific Registry of Transplant Recipient data from 2019 to 2021, we evaluated the number of transplantation centers and candidates required to place livers in the precircles and postcircles eras, nationally and by donor region. Compared with the precircles era, livers were offered to more candidates (5 vs. 9; p < 0.001) and centers (3 vs. 5; p < 0.001) before being accepted; more centers were involved in the match run by offer number 50 (9 vs. 14; p < 0.001); CIT increased by 0.2 h (5.9 h vs. 6.1 h; p < 0.001); and distribution time increased by 2.0 h (30.6 h vs. 32.6 h; p < 0.001). Increased burden varied geographically by donor region; livers recovered in Region 9 were offered to many more candidates (4 vs. 12; p < 0.001) and centers (3 vs. 8; p < 0.001) before being accepted, resulting in the largest increase in CIT (5.4 h vs. 6.0 h; p < 0.001). Circle-based allocation is associated with increased logistical burdens that are geographically heterogeneous. Continuous distribution systems will have to be carefully designed to avoid exacerbating this problem.

Life expectancy without a transplant for status 1A liver transplant candidates.

Status 1A liver transplant candidates are given the highest medical priority for the allocation of deceased donor livers. Organ Procurement and Transplantation Network (OPTN) policy requires physicians to certify that a candidate has a life expectancy without a transplant of less than 7 days for that candidate to be given status 1A. Additionally, candidates receiving status 1A must have one of six medical conditions listed in policy. Using Scientific Registry of Transplant Recipients data from all prevalent liver transplant candidates from 2010 to 2020, we used a bias-corrected Kaplan-Meier model to calculate the survival of status 1A candidates and to determine their life expectancy without a transplant. We found that status 1A candidates have a life expectancy without a transplant of 24 (95% CI 20-46) days-over three times longer than what policy requires for status 1A designation. We repeated the analysis for subgroups of status 1A candidates based on the medical conditions that grant status 1A. We found that none of these subgroups met the life expectancy requirement. Harmonizing OPTN policy with observed data would sustain the integrity of the allocation process.

MELD 3.0: The Model for End-Stage Liver Disease Updated for the Modern Era.

BACKGROUND & AIMS: The Model for End-Stage Liver Disease (MELD) has been established as a reliable indicator of short-term survival in patients with end-stage liver disease. The current version (MELDNa), consisting of the international normalized ratio and serum bilirubin, creatinine, and sodium, has been used to determine organ allocation priorities for liver transplantation in the United States. The objective was to optimize MELD further by taking into account additional variables and updating coefficients with contemporary data. METHODS: All candidates registered on the liver transplant wait list in the US national registry from January 2016 through December 2018 were included. Uni- and multivariable Cox models were developed to predict survival up to 90 days after wait list registration. Model fit was tested using the concordance statistic (C-statistic) and reclassification, and the Liver Simulated Allocation Model was used to estimate the impact of replacing MELDNa with the new model. RESULTS: The final multivariable model was characterized by (1) additional variables of female sex and serum albumin, (2) interactions between bilirubin and sodium and between albumin and creatinine, and (3) an upper bound for creatinine at 3.0 mg/dL. The final model (MELD 3.0) had better discrimination than MELDNa (C-statistic, 0.869 vs 0.862; P < .01). Importantly, MELD 3.0 correctly reclassified a net of 8.8% of decedents to a higher MELD tier, affording them a meaningfully higher chance of transplantation, particularly in women. In the Liver Simulated Allocation Model analysis, MELD 3.0 resulted in fewer wait list deaths compared to MELDNa (7788 vs 7850; P = .02). CONCLUSION: MELD 3.0 affords more accurate mortality prediction in general than MELDNa and addresses determinants of wait list outcomes, including the sex disparity.

Correcting the sex disparity in MELD-Na.

MELD-Na appears to disadvantage women awaiting liver transplant by underestimating their mortality rate. Fixing this problem involves: (1) estimating the magnitude of this disadvantage separately for each MELD-Na, (2) designing a correction for each MELD-Na, and (3) evaluating corrections to MELD-Na using simulated allocation. Using Kaplan-Meier modeling, we calculated 90-day without-transplant survival for men and women, separately at each MELD-Na. For most scores between 15 and 35, without-transplant survival was higher for men by 0-5 percentage points. We tested two proposed corrections to MELD-Na (MELD-Na-MDRD and MELD-GRAIL-Na), and one correction we developed (MELD-Na-Shift) to target the differences we quantified in survival across the MELD-Na spectrum. In terms of without-transplant survival, MELD-Na-MDRD overcorrected sex differences while MELD-GRAIL-Na and MELD-Na-Shift eliminated them. Estimating the impact of implementing these corrections with the liver simulated allocation model, we found that MELD-Na-Shift alone eliminated sex disparity in transplant rates (p = 0.4044) and mortality rates (p = 0.7070); transplant rates and mortality rates were overcorrected by MELD-Na-MDRD (p = 0.0025, p = 0.0006) and MELD-GRAIL-Na (p = 0.0079, p = 0.0005). We designed a corrected MELD-Na that eliminates sex disparities in without-transplant survival, but allocation changes directing smaller livers to shorter candidates may also be needed to equalize women's access to liver transplant.

Liver simulated allocation model does not effectively predict organ offer decisions for pediatric liver transplant candidates.

The SRTR maintains the liver-simulated allocation model (LSAM), a tool for estimating the impact of changes to liver allocation policy. Integral to LSAM is a model that predicts the decision to accept or decline a liver for transplant. LSAM implicitly assumes these decisions are made identically for adult and pediatric liver transplant (LT) candidates, which has not been previously validated. We applied LSAM's decision-making models to SRTR offer data from 2013 to 2016 to determine its efficacy for adult (≥18) and pediatric (<18) LT candidates, and pediatric subpopulations-teenagers (≥12 to <18), children (≥2 to <12), and infants (<2)-using the area under the receiver operating characteristic (ROC) curve (AUC). For nonstatus 1A candidates, all pediatric subgroups had higher rates of offer acceptance than adults. For non-1A candidates, LSAM's model performed substantially worse for pediatric candidates than adults (AUC 0.815 vs. 0.922); model performance decreased with age (AUC 0.898, 0.806, 0.783 for teenagers, children, and infants, respectively). For status 1A candidates, LSAM also performed worse for pediatric than adult candidates (AUC 0.711 vs. 0.779), especially for infants (AUC 0.618). To ensure pediatric candidates are not unpredictably or negatively impacted by allocation policy changes, we must explicitly account for pediatric-specific decision making in LSAM.

The Precise Relationship Between Model for End-Stage Liver Disease and Survival Without a Liver Transplant.

BACKGROUND AND AIMS: Scores from the Model for End-Stage Liver Disease (MELD), which are used to prioritize candidates for deceased donor livers, are widely acknowledged to be negatively correlated with the 90-day survival rate without a liver transplant. However, inconsistent and outdated estimates of survival probabilities by MELD preclude useful applications of the MELD score. APPROACH AND RESULTS: Using data from all prevalent liver waitlist candidates from 2016 to 2019, we estimated 3-day, 7-day, 14-day, 30-day, and 90-day without-transplant survival probabilities (with confidence intervals) for each MELD score and status 1A. We used an adjusted Kaplan-Meier model to avoid unrealistic assumptions and multiple observations per person instead of just the observation at listing. We found that 90-day without-transplant survival has improved over the last decade, with survival rates increasing >10% (in absolute terms) for some MELD scores. We demonstrated that MELD correctly prioritizes candidates in terms of without-transplant survival probability but that status 1A candidates' short-term without-transplant survival is higher than that of MELD 40 candidates and lower than that of MELD 39 candidates. Our primary result is the updated survival functions themselves. CONCLUSIONS: We calculated without-transplant survival probabilities for each MELD score (and status 1A). The survival function is an invaluable tool for many applications in liver transplantation: awarding of exception points, calculating the relative demand for deceased donor livers in different geographic areas, calibrating the pediatric end-stage liver disease score, and deciding whether to accept an offered liver.

Heterogeneous Circles for Liver Allocation.

BACKGROUND AND AIMS: In February 2020, the Organ Procurement and Transplantation Network replaced donor service area-based allocation of livers with acuity circles, a system based on three homogeneous circles around each donor hospital. This system has been criticized for neglecting to consider varying population density and proximity to coast and national borders. APPROACH AND RESULTS: Using Scientific Registry of Transplant Recipients data from July 2013 to June 2017, we designed heterogeneous circles to reduce both circle size and variation in liver supply/demand ratios across transplant centers. We weighted liver demand by Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) because higher MELD/PELD candidates are more likely to be transplanted. Transplant centers in the West had the largest circles; transplant centers in the Midwest and South had the smallest circles. Supply/demand ratios ranged from 0.471 to 0.655 livers per MELD-weighted incident candidate. Our heterogeneous circles had lower variation in supply/demand ratios than homogeneous circles of any radius between 150 and 1,000 nautical miles (nm). Homogeneous circles of 500 nm, the largest circle used in the acuity circles allocation system, had a variance in supply/demand ratios 16 times higher than our heterogeneous circles (0.0156 vs. 0.0009) and a range of supply/demand ratios 2.3 times higher than our heterogeneous circles (0.421 vs. 0.184). Our heterogeneous circles had a median (interquartile range) radius of only 326 (275-470) nm but reduced disparities in supply/demand ratios significantly by accounting for population density, national borders, and geographic variation of supply and demand. CONCLUSIONS: Large homogeneous circles create logistical burdens on transplant centers that do not need them, whereas small homogeneous circles increase geographic disparity. Using carefully designed heterogeneous circles can reduce geographic disparity in liver supply/demand ratios compared with homogeneous circles of radius ranging from 150 to 1,000 nm.