Liver transplantation in the United States during the COVID-19 pandemic: National and center-level responses

COVID-19 has profoundly affected the American health care system; its effect on the liver transplant (LT) waitlist based on COVID-19 incidence has not been characterized. Using SRTR data, we compared observed LT waitlist registrations, waitlist mortality, deceased donor LTs (DDLT), and living donor LTs (LDLT) 3/15/2020-8/31/2020 to expected values based on historical trends 1/2016-1/2020, stratified by statewide COVID-19 incidence. Overall, from 3/15 to 4/30, new listings were 11% fewer than expected (IRR = _0.84 0.89_0.93), LDLTs were 49% fewer (IRR = _0.37 0.51_0.72), and DDLTs were 9% fewer (IRR = _0.85 0.91_0.97). In May, new listings were 21% fewer (IRR = _0.74 0.79_0.84), LDLTs were 42% fewer (IRR = _0.39 0.58_0.85) and DDLTs were 13% more (IRR = _1.07 1.15_1.23). Centers in states with the highest incidence 3/15-4/30 had 59% more waitlist deaths (IRR = _1.09 1.59_2.32) and 34% fewer DDLTs (IRR = _0.50 0.66_0.86). By August, waitlist outcomes were occurring at expected rates, except for DDLT (13% more across all incidences). While the early COVID-affected states endured major transplant practice changes, later in the pandemic the newly COVID-affected areas were not impacted to the same extent. These results speak to the adaptability of the transplant community in addressing the pandemic and applying new knowledge to patient care.     

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.     

Mortality among solid organ waitlist candidates during COVID-19 in the United States

We examined the effects of COVID-19 on solid organ waiting list mortality in the United States and compared effects across patient demographics (e.g., race, age, and sex) and donation service areas. Three separate piecewise exponential survival models estimated for each solid organ the overall, demographic-specific, and donation service area-specific differences in the hazard of waitlist mortality before and after the national emergency declaration on March 13, 2020. Kidney waiting list mortality was higher after than before the national emergency (adjusted hazard ratio [aHR], 1.37; 95% CI, 1.23–1.52). The hazard of waitlist mortality was not significantly different before and after COVID-19 for liver (aHR, 0.94), pancreas (aHR, 1.01), lung (aHR, 1.00), and heart (aHR, 0.94). Kidney candidates had notable variability in differences across donation service areas (aHRs, New York City, 2.52; New Jersey, 1.84; and Michigan, 1.56). The only demographic group with increased waiting list mortality were Blacks versus Whites (aHR, 1.41; 95% CI, 1.07–1.86) for kidney candidates. The first 10 weeks after the declaration of a national emergency had a heterogeneous effect on waitlist mortality rate, varying by geography and ethnicity. This heterogeneity will complicate comparisons of transplant program performance during COVID-19.     

Integrating kidney transplantation into value‐based care for people with renal failure

Healthcare reimbursement is increasingly tied to value instead of volume, with special attention paid to resource‐intensive populations such as patients with renal disease. To this end, Medicare has sponsored pilot projects to encourage providers to develop care coordination and population health management strategies to provide quality care while reducing resource utilization. In this Personal Viewpoint essay, we argue in favor of expanding one such pilot project—the Comprehensive ESRD Care (CEC) initiative—to include patients with advanced chronic kidney disease and kidney transplant recipients. The implementation of the Medicare Access and CHIP Reauthorization Act (MACRA) offers a time‐sensitive incentive for transplant centers in particular to align with extant CECs. An “expanded” CEC model proffers opportunity for robust cooperation between general nephrology practices, dialysis providers, and transplant centers to develop care coordination strategies for all patients with renal disease, realign incentives for all clinical stakeholders to increase kidney transplantation rates, and reduce total costs of care.     

Impact of the new kidney allocation system A2/A2B → B policy on access to transplantation among minority candidates

Blood group B candidates, many of whom represent ethnic minorities, have historically had diminished access to deceased donor kidney transplantation (DDKT). The new national kidney allocation system (KAS) preferentially allocates blood group A2/A2B deceased donor kidneys to B recipients to address this ethnic and blood group disparity. No study has yet examined the impact of KAS on A2 incompatible (A2i) DDKT for blood group B recipients overall or among minorities. A case‐control study of adult blood group B DDKT recipients from 2013 to 2017 was performed, as reported to the Scientific Registry of Transplant Recipients. Cases were defined as recipients of A2/A2B kidneys, whereas controls were all remaining recipients of non‐A2/A2B kidneys. A2i DDKT trends were compared from the pre‐KAS (1/1/2013‐12/3/2014) to the post‐KAS period (12/4/2014‐2/28/2017) using multivariable logistic regression. Post‐KAS, there was a 4.9‐fold increase in the likelihood of A2i DDKT, compared to the pre‐KAS period (odds ratio [OR] 4.92, 95% confidence interval [CI] 3.67‐6.60). However, compared to whites, there was no difference in the likelihood of A2i DDKT among minorities post‐KAS. Although KAS resulted in increasing A2/A2B→B DDKT, the likelihood of A2i DDKT among minorities, relative to whites, was not improved. Further discussion regarding A2/A2B→B policy revisions aiming to improve DDKT access for minorities is warranted.     

Association of Candidate Removals From the Kidney Transplant Waiting List and Center Performance Oversight

Approximately 59 000 kidney transplant candidates have been removed from the waiting list since 2000 for reasons other than transplantation, death, or transfers. Prior studies indicate that low‐performance (LP) center evaluations by the Scientific Registry of Transplant Recipients (SRTR) are associated with reductions in transplant volume. There is limited information to determine whether performance oversight impacts waitlist management. We used national SRTR data to evaluate outcomes of 315 796 candidates on the kidney transplant waiting list (2007–2014). Compared to centers without LP, rates of waitlist removal (WLR) were higher at centers with LP evaluations (44.6/1000 follow‐up years, 95% confidence interval [CI] 44.0, 45.1 versus 68.0/1000 follow‐up years, 95% CI 66.6, 69.4), respectively, which was consistent after risk adjustment (adjusted hazard ratio [AHR] = 1.59, 95% CI 1.55, 1.63). Candidate mortality following waitlist removal was lower at LP centers (AHR = 0.90, 95% CI 0.87, 0.94). Analyses limited to LP centers indicated a significant increase in WLR (+28.6 removals/1000 follow‐up years, p < 0.001), a decrease in transplant rates (?11.9/1000 follow‐up years, p < 0.001) and a decrease in mortality after removal (?67.5 deaths/1000 follow‐up years, p < 0.001) following LP evaluation. There is a significant association between LP evaluations and transplant center processes of care for waitlisted candidates. Further understanding is needed to determine the impact of performance oversight on transplant center quality of care and patient outcomes.

     

Gender Disparities in Access to Pediatric Renal Transplantation in Europe: Data From the ESPN/ERA‐EDTA Registry

Inequalities between genders in access to transplantation have been demonstrated. We aimed to validate this gender inequality in a large pediatric population and to investigate its causes. This cohort study included 6454 patients starting renal replacement therapy before 18 years old, in 35 countries participating in the European Society for Paediatric Nephrology/European Renal Association–European Dialysis and Transplant Association Registry. We used cumulative incidence competing risk and proportional hazards frailty models to study the time to receive a transplant and hierarchical logistic regression to investigate access to preemptive transplantation. Girls had a slower access to renal transplantation because of a 23% lower probability of receiving preemptive transplantation. We found a longer follow‐up time before renal replacement therapy in boys compared with girls despite a similar estimated glomerular filtration rate at first appointment. Girls tend to progress faster toward end‐stage renal disease than boys, which may contribute to a shorter time available for pretransplantation workup. Overall, medical factors explained only 70% of the gender difference. In Europe, girls have less access to preemptive transplantation for reasons that are only partially related to medical factors. Nonmedical factors such as patient motivation and parent and physician attitudes toward transplantation and organ donation may contribute to this inequality. Our study should raise awareness for the management of girls with renal diseases.     

COVID-19 in pediatric kidney transplantation: The Improving Renal Outcomes Collaborative

There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes.     

Temporal trends in utilization and outcomes of steatotic donor livers in the United States

Steatotic donor livers (SDLs) (macrosteatosis ≥30%) represent a possible donor pool expansion, but are frequently discarded due to a historical association with mortality and graft loss. However, changes in recipient/donor demographics, allocation policy, and clinical protocols might have altered utilization and outcomes of SDLs. We used Scientific Registry of Transplant Recipients data from 2005 to 2017 and adjusted multilevel regression to quantify temporal trends in discard rates (logistic) and posttransplant outcomes (Cox) of SDLs, accounting for Organ Procurement Organization–level variation. Of 4346 recovered SDLs, 58.0% were discarded in 2005, versus only 43.1% in 2017 (P < .001). SDLs were always substantially more likely discarded versus non‐SDLs, although this difference decreased over time (adjusted odds ratio in 2005‐2007:_13.1515.28_17.74; 2008‐2011:_11.7713.41_15.29; 2012‐2014:_9.8711.37_13.10; 2015‐2017:_7.798.89_10.15, P < .001 for all). Conversely, posttransplant outcomes of recipients of SDLs improved over time: recipients of SDLs from 2012 to 2017 had 46% lower risk of mortality (adjusted hazard ratio [aHR]: _0.430.54_0.68, P < .001) and 47% lower risk of graft loss (aHR: _0.420.53_0.67, P < .001) compared to 2005 to 2011. In fact, in 2012 to 2017, recipients of SDLs had equivalent mortality (aHR: _0.901.04_1.21, P = .6) and graft loss (aHR: _0.901.04_1.20, P = .6) to recipients of non‐SDLs. Increasing utilization of SDLs might be a reasonable strategy to expand the donor pool.     

Health Insurance Trends in United States Living Kidney Donors (2004 to 2015)

Some transplant programs consider the lack of health insurance as a contraindication to living kidney donation. Still, prior studies have shown that many adults are uninsured at time of donation. We extend the study of donor health insurance status over a longer time period and examine associations between insurance status and relevant sociodemographic and health characteristics. We queried the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry for all living kidney donors (LKDs) between July 2004 and July 2015. Of the 53 724 LKDs with known health insurance status, 8306 (16%) were uninsured at the time of donation. Younger (18 to 34 years old), male, minority, unemployed, less educated, unmarried LKDs and those who were smokers and normotensive were more likely to not have health insurance at the time of donation. Compared to those with no health risk factors (i.e. obesity, smoking, hypertension, estimated glomerular filtration rate <60, proteinuria) (14%), LKDs with 1 (18%) or ≥2 (21%) health risk factors at the time of donation were more likely to be uninsured (p < 0.0001). Among those with ≥2 health risk factors, blacks (28%) and Hispanics (27%) had higher likelihood of being uninsured compared to whites (19%; p < 0.001). Study findings underscore the importance of providing health insurance benefits to all previous and future LKDs.     

Beyond the Billboard: The Facebook‐Based Application,Donor, and Its Guided Approach to Facilitating Living Organ Donation

Living donor solicitation can raise ethical concerns, regardless of the medium used: newspaper, television, pulpit, billboard or Internet. Moving the search for a living donor into the social media realm introduces the risk of unguided and coercive patient narratives as well as decoupling or even total absence of information that could aid the consent process. The Facebook application (app) for living donors, called Donor (restricted to patient use), aims to address these concerns in several ways: (i) by directing the patient's initial appeal to friends and family; (ii) by guiding the patient's narrative; and (iii) by providing a library of clinical, ethical and regulatory information that informs the consent process. In this paper, we explored these features and contrasted them with billboard solicitation activities and current independent social media efforts. We concluded that the proactive ethical design of the Donor app is a permissible way to help satisfy the shortfall of deceased donor livers and kidneys.     

Socioeconomic Status and Ethnicity of Deceased Donor Kidney Recipients Compared to Their Donors

Public perception and misperceptions of socioeconomic disparities affect the willingness to donate organs. To improve our understanding of the flow of deceased donor kidneys, we analyzed socioeconomic status (SES) and racial/ethnic gradients between donors and recipients. In a retrospective cohort study, traditional demographic and socioeconomic factors, as well as an SES index, were compared in 56,697 deceased kidney donor and recipient pairs transplanted between 2007 and 2012. Kidneys were more likely to be transplanted in recipients of the same racial/ethnic group as the donor (p < 0.001). Kidneys tended to go to recipients of lower SES index (50.5% of the time, p < 0.001), a relationship that remained after adjusting for other available markers of donor organ quality and SES (p < 0.001). Deceased donor kidneys do not appear to be transplanted from donors of lower SES to recipients of higher SES; this information may be useful in counseling potential donors and their families regarding the distribution of their organ gifts.     

The effect of Share 35 on biliary complications: An interrupted time series analysis

The purpose of the Share 35 allocation policy was to improve liver transplant waitlist mortality, targeting high MELD waitlisted patients. However, policy changes may also have unintended consequences that must be balanced with the primary desired outcome. We performed an interrupted time series assessing the impact of Share 35 on biliary complications in a select national liver transplant population using the Vizient CDB/RM database. Liver transplants that occurred between October 2012 and September 2015 were included. There was a significant change in the incident‐rate of biliary complications between Pre‐Share 35 (n = 3018) and Post‐Share 35 (n = 9984) cohorts over time (P = .023, r² = .44). As a control, a subanalysis was performed throughout the same time period in Region 9 transplant centers, where a broad sharing agreement had previously been implemented. In the subanalysis, there was no change in the incident‐rate of biliary complications between the two time periods. Length of stay and mean direct cost demonstrated a change after implementation of Share 35, although they did not meet statistical difference. While the target of improved waitlist mortality is of utmost importance for the equitable allocation of organs, unintended consequences of policy changes should be studied for a full assessment of a policy's impact.