Faculty Bibliography

OBJECTIVE:Lung transplants from donors with hepatitis C (HCV D+) have excellent outcomes, but these organs continue to be declined. We evaluated whether (1) being listed to consider and (2) accepting versus declining HCV D+ offers provided a survival benefit to lung transplant candidates. METHODS:Using the Scientific Registry of Transplant Recipients, we identified all adult (≥18 years) lung transplant candidates 2016-2021 and compared waitlist mortality between those willing versus not willing to consider HCV D+ offers using competing risk regression. We identified all candidates offered an HCV D+ lung that was later accepted and followed them from offer decision until death or end-of-study. We estimated adjusted mortality risk of accepting versus declining an HCV D+ lung offer using propensity-weighted Cox regression. RESULTS:From 2016 to 2021, we identified 21,007 lung transplant candidates, 33.8% of whom were willing to consider HCV D+ offers. Candidates willing to consider HCV D+ offers had a 17% lower risk of waitlist mortality (subhazard ratio, 0.83; 95% confidence interval, 0.75-0.91, P < .001). Over the same period, 665 HCV D+ lung offers were accepted after being declined a total of 2562 times. HCV D+ offer acceptance versus decline was associated with a 20% lower risk of mortality (adjusted hazard ratio, 0.80; 95% confidence interval, 0.66-0.96, P = .02). CONCLUSIONS:Considering HCV D+ lung offers was associated with a 17% lower risk of waitlist mortality, whereas accepting versus declining an HCV D+ lung offer was associated with a 20% lower risk of mortality. Centers and candidates should consider accepting suitable HCV D+ lung offers to optimize outcomes.

BACKGROUND/UNASSIGNED:The HIV Organ Policy Equity Act legalizes organ procurement from donors with HIV (HIV D+). A prior survey of Organ Procurement Organizations (OPOs) estimated >2000 HIV D+ referrals/year; however, only 30-35 HIV D+/year have had organs procured. Given this gap, we sought to understand HIV D+ referrals and procurements in practice. METHODS/UNASSIGNED:We prospectively collected data on all OPO-reported HIV D+ referrals, including reasons for nonprocurement. We evaluated trends and compared HIV D+ characteristics by procurement status using regression, chi-squared tests, and Wilcoxon rank-sum tests. RESULTS/UNASSIGNED: < 0.001). Nonprocurement was attributed to medical reasons in 63% of cases, of which 36% were AIDS-defining infections and 64% were HIV-unrelated, commonly due to organ failure (36%), high neurologic function (31%), and cancer (14%). Nonprocurement was attributed to nonmedical reasons in 26% of cases, commonly due to no authorization (42%), no waitlist candidates (21%), or no transplant center interest (20%). CONCLUSIONS/UNASSIGNED:In the early years of the HIV Organ Policy Equity Act, actual HIV D+ referrals were much lower than prior estimates; however, the numbers and procurement rates increased over time. Nonprocurement was attributed to both medical and nonmedical issues, and addressing these issues could increase organ availability.

Background. The HIV Organ Policy Equity Act legalizes organ procurement from donors with HIV (HIV D+). A prior survey of Organ Procurement Organizations (OPOs) estimated >2000 HIV D+ referrals/year; however, only 30"“35 HIV D+/ year have had organs procured. Given this gap, we sought to understand HIV D+ referrals and procurements in practice. Methods. We prospectively collected data on all OPO-reported HIV D+ referrals, including reasons for nonprocurement. We evaluated trends and compared HIV D+ characteristics by procurement status using regression, chi-squared tests, and Wilcoxon rank-sum tests. Results. From December 23, 2015 to May 31, 2021, there were 710 HIV D+ referrals from 49 OPOs, of which 171 (24%) had organs procured. HIV D+ referrals increased from 7 to 15 per month (P < 0.001), and the procurement rate increased from 10% to 39% (P < 0.001). Compared with HIV D+ without procurement, HIV D+ with procurement were younger (median age 36 versus 50 y), more commonly White (46% versus 36%), and more often had trauma-related deaths (29% versus 8%) (all P < 0.001). Nonprocurement was attributed to medical reasons in 63% of cases, of which 36% were AIDS-defining infections and 64% were HIV-unrelated, commonly due to organ failure (36%), high neurologic function (31%), and cancer (14%). Nonprocurement was attributed to nonmedical reasons in 26% of cases, commonly due to no authorization (42%), no waitlist candidates (21%), or no transplant center interest (20%). Conclusions. In the early years of the HIV Organ Policy Equity Act, actual HIV D+ referrals were much lower than prior estimates; however, the numbers and procurement rates increased over time. Nonprocurement was attributed to both medical and nonmedical issues, and addressing these issues could increase organ availability.

Since the development of the first heart allocation system in 1988 to the most recent heart allocation system in 2018, the road to heart transplantation has continued to evolve. Policies were shaped with advances in temporary and durable left ventricular assist devices as well as prioritization of patients based on degree of illness. Herein, we review the changes in the heart allocation system over the past several decades and the impact of practice patterns across the United States.

Kidney transplantation from blood type A2/A2B donors to type B recipients (A2→B) has increased dramatically under the current Kidney Allocation System (KAS). Among living donor transplant recipients, A2-incompatible transplants are associated with an increased risk of all-cause and death-censored graft failure. In light of this, we used SRTR data from 12/2014-6/2022 to evaluate the association between A2→B listing and time to deceased donor kidney transplantation (DDKT) and post-DDKT outcomes for A2→B recipients. Among 53,409 type B waitlist registrants, only 12.6% were listed as eligible to accept A2→B offers ("A2-eligible"). 1-/3-/5-year DDKT rates were 32.1%/61.4%/72.1% among A2-eligible candidates and 14.1%/29.9%/44.1% among A2-ineligible candidates, with the former experiencing a 133% higher rate of DDKT (Cox weighted HR = _2.192.33_2.47; p<0.001). The 7-year adjusted mortality was comparable between A2→B and B-ABOc (type B/O donors to B recipients) recipients (wHR _0.780.94_1.13, p=0.5). Moreover, there was no difference between A2→B vs. B-ABOc DDKT recipients with regards to death-censored graft failure (wHR _0.771.00_1.29, p>0.9) or all-cause graft loss (wHR _0.820.96_1.12, p=0.6). Following its broader adoption since the implementation of KAS, A2→B DDKT appears to be a safe and effective transplant modality for eligible candidates. As such, A2→B listing for eligible type B candidates should be expanded.

BACKGROUND:Cytomegalovirus (CMV)-seronegative lung transplant recipients (LTRs) with seropositive donors (CMV D+/R-) have the highest mortality of all CMV serostatuses. Due to immunosenescence and other factors, we hypothesized CMV D+/R- status might disproportionately impact older LTRs. Thus, we investigated whether recipient age modified the relationship between donor CMV status and mortality among CMV-seronegative LTRs. METHODS:Adult, CMV-seronegative first-time lung-only recipients were identified through the Scientific Registry of Transplant Recipients between May 2005 and December 2019. We used adjusted multivariable Cox regression to assess the relationship of donor CMV status and death. Interaction between recipient age and donor CMV was assessed via likelihood ratio testing of nested Cox models and by the relative excess risk due to interaction (RERI) and attributable proportion (AP) of joint effects. RESULTS:We identified 11,136 CMV-seronegative LTRs. The median age was 59 years; 65.2% were male, with leading transplant indication of idiopathic pulmonary fibrosis (35.6%); and 60.8% were CMV D+/R-. In multivariable modeling, CMV D+/R- status was associated with 27% increased hazard of death (adjusted hazard ratio: 1.27, 95% confidence interval: 1.21-1.34) compared to CMV D-/R-. Recipient age ≥60 years significantly modified the relationship between donor CMV-seropositive status and mortality on the additive scale, including RERI 0.24 and AP 11.4% (p = 0.001), that is, the interaction increased hazard of death by 0.24 and explained 11.4% of mortality in older CMV D+ recipients. CONCLUSIONS:Among CMV-seronegative LTRs, donor CMV-seropositive status confers higher risk of posttransplant mortality, which is amplified in older recipients. Future studies should define optimal strategies for CMV prevention and management in older D+/R- LTRs.

BACKGROUND:Since February 2020, exception points have been allocated equivalent to the median model for end-stage liver disease at transplant within 250 nautical miles of the transplant center (MMaT/250). We compared transplant rate and waitlist mortality for hepatocellular carcinoma (HCC) exception, non-HCC exception, and non-exception candidates to determine whether MMaT/250 advantages (or disadvantages) exception candidates. METHODS:Using Scientific Registry of Transplant Recipients data, we identified 23 686 adult, first-time, active, deceased donor liver transplant (DDLT) candidates between February 4, 2020, and February 3, 2022. We compared DDLT rates using Cox regression, and waitlist mortality/dropout using competing risks regression in non-exception versus HCC versus non-HCC candidates. RESULTS:Within 24 mo of study entry, 58.4% of non-exception candidates received DDLT, compared with 57.8% for HCC candidates and 70.5% for non-HCC candidates. After adjustment, HCC candidates had 27% lower DDLT rate (adjusted hazard ratio = 0.680.730.77) compared with non-exception candidates. However, waitlist mortality for HCC was comparable to non-exception candidates (adjusted subhazard ratio [asHR] = 0.931.031.15). Non-HCC candidates with pulmonary complications of cirrhosis or cholangiocarcinoma had substantially higher risk of waitlist mortality compared with non-exception candidates (asHR = 1.271.702.29 for pulmonary complications of cirrhosis, 1.352.043.07 for cholangiocarcinoma). The same was not true of non-HCC candidates with exceptions for other reasons (asHR = 0.540.881.44). CONCLUSIONS:Under MMaT/250, HCC, and non-exception candidates have comparable risks of dying before receiving liver transplant, despite lower transplant rates for HCC. However, non-HCC candidates with pulmonary complications of cirrhosis or cholangiocarcinoma have substantially higher risk of dying before receiving liver transplant; these candidates may merit increased allocation priority.

BACKGROUND:Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D+), it is crucial to understand whether this has impacted transplant rates for this population. METHODS:Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D+ kidneys (HOPE) compared with 46 025 candidates not listed for D+ kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D+, false-positive [FP; donor with false-positive HIV testing], D- [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS:HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P < 0.001). Within 4.5 y, 70% of HOPE candidates received a KT (41% D+, 34% D-, 20% FP, 4% LD) versus 43% of non-HOPE candidates (74% D-, 26% LD). Conversely, 22% of HOPE candidates versus 39% of non-HOPE candidates died or were removed from the waitlist. Median KT wait time was 10.3 mo for HOPE versus 60.8 mo for non-HOPE candidates (P < 0.001). After adjustment, HOPE candidates had a 3.30-fold higher KT rate (adjusted hazard ratio = 3.30, 95% confidence interval, 2.14-5.10; P < 0.001). CONCLUSIONS:Listing for D+ kidneys within HOPE trials was associated with a higher KT rate and shorter wait time, supporting the expansion of this practice for candidates with HIV.

BACKGROUND:Organs from Public Health Service criteria (PHSC) donors, previously referred to as PHS infectious-risk donors, have historically been recovered but not used, traditionally referred to as "discard," at higher rates despite negligible risk to recipients. On March 1, 2021, the definition of PHSC donors narrowed to include only the subset of donors deemed to have meaningfully elevated risk in the current era of improved infectious disease testing. METHODS:Using Scientific Registry of Transplant Recipients data from May 1, 2019, to December 31, 2022, we compared rates of PHSC classification and nonutilization of PHSC organs before versus after the March 1, 2021, policy change among recovered decedents using the χ2 tests. We performed an adjusted interrupted time series analysis to examine kidney and liver recovery/nonuse (traditionally termed "discard") and kidney, liver, lung, and heart nonutilization (nonrecovery or recovery/nonuse) prepolicy versus postpolicy. RESULTS:PHSC classification dropped sharply from 24.5% prepolicy to 15.4% postpolicy (P < 0.001). Before the policy change, PHSC kidney recovery/nonuse, liver nonuse, lung nonuse, and heart nonuse were comparable to non-PHSC estimates (adjusted odds ratio: kidney = 0.981.061.14, P = 0.14; liver = 0.850.921.01, P = 0.07; lung = 0.910.991.08, P = 0.83; heart = 0.890.971.05, P = 0.47); following the policy change, PHSC kidney recovery/nonuse, liver nonuse, lung nonuse, and heart nonuse were lower than non-PHSC estimates (adjusted odds ratio: kidney = 0.770.840.91, P < 0.001; liver = 0.770.840.92, P < 0.001; lung = 0.740.810.90, P < 0.001; heart = 0.610.670.73, P < 0.001). CONCLUSIONS:Even though PHSC donors under the new definition are a narrower and theoretically riskier subpopulation than under the previous classification, PHSC status appears to be associated with a reduced risk of kidney and liver recovery/nonuse and nonutilization of all organs. Although historically PHSC organs have been underused, our findings demonstrate a notable shift toward increased PHSC organ utilization.

OBJECTIVE:End-stage lung disease from severe COVID-19 infection is an increasingly common indication for lung transplantation (LT), but there are limited data on outcomes. We evaluated 1-year COVID-19 LT outcomes. METHODS:We identified all adult US LT recipients January 2020 to October 2022 in the Scientific Registry for Transplant Recipients, using diagnosis codes to identify recipients transplanted for COVID-19. We used multivariable regression to compare in-hospital acute rejection, prolonged ventilator support, tracheostomy, dialysis, and 1-year mortality between COVID-19 and non-COVID-19 recipients, adjusting for donor, recipient, and transplant characteristics. RESULTS:LT for COVID-19 increased from 0.8% to 10.7% of total LT volume during 2020 to 2021. The number of centers performing LT for COVID-19 increased from 12 to 50. Recipients transplanted for COVID-19 were younger; were more likely to be male and Hispanic; were more likely to be on a ventilator, extracorporeal membrane oxygenation support, and dialysis pre-LT; were more likely to receive bilateral LT; and had higher lung allocation score and shorter waitlist time than other recipients (all P values < .001). COVID-19 LT had higher risk of prolonged ventilator support (adjusted odds ratio, 2.28; P < .001), tracheostomy (adjusted odds ratio 5.3; P < .001), and longer length of stay (median, 27 vs 19 days; P < .001). Risk of in-hospital acute rejection (adjusted odds ratio, 0.99; P = .95) and 1-year mortality (adjusted hazard ratio, 0.73; P = .12) were similar for COVID-19 LTs and LTs for other indications, even accounting for center-level differences. CONCLUSIONS:COVID-19 LT is associated with higher risk of immediate postoperative complications but similar risk of 1-year mortality despite more severe pre-LT illness. These encouraging results support the ongoing use of LT for COVID-19-related lung disease.