Faculty Bibliography

BACKGROUND:Historically, donation after circulatory death (DCD) livers were frequently discarded due to higher mortality and graft loss after liver transplantation (LT). However, the demand for liver transplantation continues to outstrip the supply of "acceptable" organs. Additionally, changes in the donor pool, organ allocation, clinical management of donors and recipients, and improved clinical protocols might have altered post-DCD-LT outcomes. METHODS:We studied 5,975 recovered DCD livers using U.S. SRTR data from 2005-2017, with a comparison group of 78,235 adult DBD livers recovered during the same time period. We quantified temporal trends in discard using adjusted multilevel logistic regression and temporal trends in post-LT mortality and graft loss for DCD LT recipients using adjusted Cox regression. RESULTS:DCD livers were more likely to be discarded than DBD livers across the entire study period, and the relative likelihood of discard increased over time (adjusted odds ratio [aOR] of discard DCD vs. DBD 3.854.455.14 2005-2007, 5.225.876.59 2015-2017) despite improving outcomes after DCD LT. Mortality risk for DCD LTs decreased in each time period (compared to 2005-2007, aHR 2008-2011 0.720.840.97, aHR 2012-2014 0.480.580.70, aHR 2015-2017 0.340.430.55), as did risk of graft loss (compared to 2005-2007, aHR 2008-2011 0.690.810.94, aHR 2012-2014 0.450.550.67, aHR 2015-2017 0.360.450.56). CONCLUSIONS:Despite dramatic improvements in outcomes of DCD LT recipients, DCD livers remain substantially more likely to be discarded than DBD livers, and this discrepancy has actually increased over time. DCD livers are underutilized and have the potential to expand the donor pool.

Acuity circles (AC), the new liver allocation system, was implemented on February 4, 2020. Difference-in-differences analyses estimated the effect of AC on adjusted deceased donor transplant and offer rates across Pediatric End-Stage Liver Disease (PELD) and Model for End-Stage Liver Disease (MELD) categories and types of exception statuses. The offer rates were the number of first offers, top 5 offers, and top 10 offers on the match run per person-year. Each analysis adjusted for candidate characteristics and only used active candidate time on the waiting list. The before-AC period was February 4, 2019, to February 3, 2020, and the after-AC period was February 4, 2020, to February 3, 2021. Candidates with PELD/MELD scores 29 to 32 and PELD/MELD scores 33 to 36 had higher transplant rates than candidates with PELD/MELD scores 15 to 28 after AC compared with before AC (transplant rate ratios: PELD/MELD scores 29-32, _2.34 3.32_4.71 ; PELD/MELD scores 33-36, _1.70 2.51_3.71 ). Candidates with PELD/MELD scores 29 or higher had higher offer rates than candidates with PELD/MELD scores 15 to 28, and candidates with PELD/MELD scores 29 to 32 had the largest difference (offer rate ratios [ORR]: first offers, _2.77 3.95_5.63 ; top 5 offers, _3.90 4.39_4.95 ; top 10 offers, _4.85 5.30_5.80 ). Candidates with exceptions had lower offer rates than candidates without exceptions for offers in the top 5 (ORR: hepatocellular carcinoma [HCC], _0.68 0.77_0.88 ; non-HCC, _0.73 0.81_0.89 ) and top 10 (ORR: HCC, _0.59 0.65_0.71 ; non-HCC, _0.69 0.75_0.81 ). Recipients with PELD/MELD scores 15 to 28 and an HCC exception received a larger proportion of donation after circulatory death (DCD) donors after AC than before AC, although the differences in the liver donor risk index were comparatively small. Thus, candidates with PELD/MELD scores 29 to 34 and no exceptions had better access to transplant after AC, and donor quality did not notably change beyond the proportion of DCD donors.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p > .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

BACKGROUND:The purpose of this study was to evaluate outcomes in people with cystic fibrosis (CF) who underwent lung transplant (LT) at a transplant center with an accredited Cystic Fibrosis Care Center (CFCC) in the United States. METHODS:We reviewed the Scientific Registry of Transplant Recipients for all adult patients with CF who received a first-time LT from 2005 to 2018. The primary outcome was graft failure. Unadjusted Kaplan-Meier analysis and adjusted multilevel Cox proportional hazards models were used to evaluate outcomes in CF patients undergoing lung transplantation at a CFCC. RESULTS:2,573 patients with CF underwent a first time LT during the study period. Of the 68 lung transplantation centers, 50 were CFCCs (73.5%). After adjustment for potential confounders, patients who underwent lung transplantation at a hospital with an accredited CFCC had a 33% reduction in risk of death or re-transplantation compared to those transplanted at a hospital without an accredited CFCC (HR: 0.67, 95% CI: 0.56-0.82, p < 0.001). CONCLUSIONS:People with CF who undergo LT at a transplant center with a CFCC have improved graft survival and decreased need for re-transplantation compared to those who undergo LT at a non-CFCC, independent of volume.

BACKGROUND:Frailty predicts adverse post-kidney transplant (KT) outcomes, yet the impact of frailty assessment on center-level outcomes remains unclear. We sought to test whether transplant centers assessing frailty as part of clinical practice have better pre- and post-KT outcomes in all adult patients (≥18 years) and older patients (≥65 years). METHODS:In a survey of US transplant centers (11/2017-4/2018), 132 (response rate = 65.3%) centers reported their frailty assessment practices (frequency and specific tool) at KT evaluation and admission. Assessment frequency was categorized as never, sometime, and always; type of assessment tool was categorized as none, validated (for post-KT risk prediction), and any other tool. Center characteristics and clinical outcomes for adult patients during 2017-2019 were gleaned from the transplant national registry (Scientific Registry of Transplant Recipients). Poisson regression was used to estimate incidence rate ratios (IRRs) of waitlist outcomes (waitlist mortality, transplantation) in candidates and IRRs of post-KT outcomes (all-cause mortality, death-censored graft loss) in recipients by frailty assessment frequency. We also estimated IRRs of waitlist outcomes by type of assessment tool at evaluation. All models were adjusted for case mix and center characteristics. RESULTS:Assessing frailty at evaluation was associated with lower waitlist mortality rate (always IRR = 0.91,95%CI:0.84-0.99; sometimes = 0.89,95%CI:0.83-0.96) and KT rate (always = 0.94,95%CI:0.91-0.97; sometimes = 0.88,95%CI:0.85-0.90); the associations with waitlist mortality rate (always = 0.86,95%CI:0.74-0.99; sometimes = 0.83,95%CI:0.73-0.94) and KT rate (always = 0.82,95%CI:0.77-0.88; sometimes = 0.92,95%CI:0.87-0.98) were stronger in older patients. Furthermore, using validated (IRR = 0.90,95%CI:0.88-0.92) or any other tool (IRR = 0.90,95%CI:0.87-0.93) at evaluation was associated lower KT rate, while only using a validated tool was associated with lower waitlist mortality rate (IRR = 0.89,95%CI:0.83-0.96), especially in older patients (IRR = 0.82,95%CI:0.72-0.93). At admission for KT, always assessing frailty was associated with a lower graft loss rate (IRR = 0.71,95%CI:0.54-0.92) but not with mortality (IRR = 0.93,95%CI:0.76-1.13). CONCLUSIONS:Assessing frailty at evaluation is associated with lower KT rate, while only using a validated frailty assessment tool is associated with better survival, particularly in older candidates. Centers always assessing frailty at admission are likely to have better graft survival rates. Transplant centers may utilize validated frailty assessment tools to secure KT access for appropriate candidates and to better allocate health care resources for patients identified as frail, particularly for older patients.