Faculty Bibliography

Importance:Traditionally, liver transplant (LT) for alcohol-associated liver disease (ALD) requires 6 months of abstinence. Although early LT before 6 months of abstinence has been associated with decreased mortality for decompensated ALD, this practice remains controversial and concentrated at a few centers. Objective:To define patient, allograft, and relapse-free survival in early LT for ALD, and to investigate the association between these survival outcomes and early vs standard LT. Design, Setting, and Participants:This cohort study analyzed all patients with ALD who underwent their first LT at a single academic referral center between October 1, 2012, and November 13, 2020. Patients with known pretransplant hepatocellular carcinoma, hepatitis B or C, or an alternative cause of liver failure were excluded. Follow-up period was defined as the time from LT to the most recent encounter with a transplant center or death. Exposures:The exposure of interest was early LT, which was defined as less than 180 days of pre-LT abstinence. Standard LT was defined as 180 days or more of pre-LT abstinence. Patients were separated into early LT and standard LT by time from abstinence to LT. Main Outcomes and Measures:The outcomes were patient, allograft, relapse-free, and hazardous relapse-free survival for patients who underwent early LT or standard LT. These groups were compared by log-rank testing of Kaplan-Meier estimates. Hazardous relapse was defined as binge, at-risk, or frequent drinking. Abstinence was reassessed at the most recent follow-up visit for all patients. Results:Of the 163 patients with ALD included in this study, 88 (54%) underwent early LT and 75 (46%) underwent standard LT. This cohort had a mean (SD) age at transplant of 52 (10) years and was predominantly composed of 108 male patients (66%). Recipients of early LT vs standard LT were younger (median [interquartile range (IQR)] age, 49.7 [39.0-54.2] years vs 54.6 [48.7-60.0] years; P < .001) and had a higher median (IQR) Model for End-stage Liver Disease score at listing (35.0 [29.0-39.0] vs 20.0 [13.0-26.0]; P < .001). Both recipients of early LT and standard LT had similar 1-year patient survival (94.1% [95% CI, 86.3%-97.5%] vs 95.9% [95% CI, 87.8%-98.7%]; P = .60), allograft survival (92.7% [95% CI, 84.4%-96.7%] vs 90.5% [95% CI, 81.0%-95.3%]; P = .42), relapse-free survival (80.4% [95% CI, 69.1%-88.0%] vs 83.5% [95% CI, 72.2%-90.6%]; P = .41), and hazardous relapse-free survival (85.8% [95% CI, 75.1%-92.2%] vs 89.6% [95% CI, 79.5%-94.9%]; P = .41). Conclusions and Relevance:Adherence to the 6-month rule was not associated with superior patient survival, allograft survival, or relapse-free survival among selected patients. This finding suggests that patients with ALD should not be categorically excluded from LT solely on the basis of 6 months of abstinence, but rather alternative selection criteria should be identified that are based on need and posttransplant outcomes.

Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralizing activity. A third SARS-CoV-2 vaccine dose increased median anti-spike (1.6-fold) and receptor-binding domain (1.5-fold) IgG, as well as pseudoneutralization against VOCs (2.5-fold versus Delta). However, IgG and neutralization activity were significantly lower than healthy controls (p<0.001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination. Correlation with nAb was seen at anti-spike IgG >4 AU on the clinical assay and >10^4 AU on the research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.

BACKGROUND:We studied the safety and reactogenicity SARS-CoV-2 mRNA vaccines in transplant recipients because immunosuppressed patients were excluded from vaccine trials. METHODS:US transplant recipients were recruited into this prospective cohort study through social media; those who completed the full vaccine series between December 9, 2020 and March 1, 2021 were included. We collected demographics, medical history, and safety information within 7 d after doses 1 and 2 (D1, D2). Associations between characteristics and reactions were evaluated using modified Poisson regression. RESULTS:We studied 741 transplant recipients who underwent BNT162b2 (54%) or mRNA-1273 (46%) vaccination. Median (interquartile range) age was 60 (44-69) y, 57% were female, and 10% were non-White. Although local site reactions decreased after D2 (85% D1 versus 78% D2, P < 0.001), systemic reactions increased (49% D1 versus 69% D2, P < 0.001). Younger participants were more likely to develop systemic symptoms after D1 (adjusted incidence rate ratio [aIRR] per 10 y = 0.850.900.94, P < 0.001) and D2 (aIRR per 10 y = 0.910.930.96, P < 0.001). Participants who experienced pain (aIRR = 1.111.662.47, P = 0.01) or redness (aIRR = 1.833.928.41, P < 0.01) were more likely to develop an antibody response to D1 of mRNA vaccines. No anaphylaxis, neurologic diagnoses, or SARS-CoV-2 diagnoses were reported. Infections were minimal (3% after D1, <0.01% after D2). One patient reported incident acute rejection post-D2. CONCLUSIONS:In solid organ transplant recipients undergoing mRNA vaccination, reactogenicity was similar to that reported in the original trials. Severe reactions were rare. These early safety data may help address vaccine hesitancy in transplant recipients.

Recently, model for end-stage liver disease (MELD)-based liver allocation in the United States has been questioned based on concerns that waitlist mortality for a given biologic MELD (bMELD), calculated using laboratory values alone, might be higher at certain centers in certain locations across the country. Therefore, we aimed to quantify the center-level variation in bMELD-predicted mortality risk. Using Scientific Registry of Transplant Recipients (SRTR) data from January 2015 to December 2019, we modeled mortality risk in 33 260 adult, first-time waitlisted candidates from 120 centers using multilevel Poisson regression, adjusting for sex, and time-varying age and bMELD. We calculated a "MELD correction factor" using each center's random intercept and bMELD coefficient. A MELD correction factor of +1 means that center's candidates have a higher-than-average bMELD-predicted mortality risk equivalent to 1 bMELD point. We found that the "MELD correction factor" median (IQR) was 0.03 (-0.47, 0.52), indicating almost no center-level variation. The number of centers with "MELD correction factors" within ±0.5 points, and between ±0.5-± 1, ±1.0-±1.5, and ±1.5-±2.0 points was 62, 41, 13, and 4, respectively. No centers had waitlisted candidates with a higher-than-average bMELD-predicted mortality risk beyond ±2 bMELD points. Given that bMELD similarly predicts waitlist mortality at centers across the country, our results support continued MELD-based prioritization of waitlisted candidates irrespective of center.

OBJECTIVES/OBJECTIVE:The creation and maintenance of durable hemodialysis access is critically important for reducing patient morbidity and controlling overall costs within health systems. Our objective was to quantify the costs associated with hemodialysis access creation and its maintenance over time within a rate-controlled health system where charges equate to payments. METHODS:The Maryland Health Services Cost Review Commission administrative claims database was used to identify patients who underwent first-time access creation from 2012-2020. Patients were identified using CPT codes for access creation, and costs were accrued for the initial encounter and all subsequent outpatient access-related encounters. T-tests and Wilcoxon tests were used to compare reinterventions and access-related costs ($USD) between arteriovenous fistulae (AVF) and arteriovenous grafts (AVG). Multivariable modeling was used to quantify the association of access type with charge variation. RESULTS:Overall, 12,716 patients underwent first-time access creation (69.3% AVF vs. 30.7% AVG). There was no difference in freedom from reintervention between the two access types at any point following creation (HR: 1.03, 95%CI: 0.97-1.10); however, AVF were associated with a lower number of cumulative reinterventions (1.50 vs. 2.24) compared to AVG (P<0.0001). AVF was associated with lower overall costs in the year of creation ($9,388 vs. $13,539, P<0.0001), a difference that remained significant over the subsequent 3 years. The lower costs associated with AVF were present both in the costs associated with creation and subsequent maintenance. On multivariable analysis, AVF was associated with a $3,557 reduction in total access-related costs versus AVG (95%CI -$3828, -3287). CONCLUSION/CONCLUSIONS:AVF require fewer interventions and are associated with lower costs at placement and over the first three years of maintenance compared to AVG. The use of AVF for first-time hemodialysis access represents an opportunity for healthcare savings in appropriately selected patients with a high preoperative likelihood of AVF maturation.

Organ procurement organizations (OPOs) evaluate referrals for deceased organ donation in the United States. Efforts to expand the donor pool, such as the HIV organ policy equity (HOPE) Act that permits transplants from HIV-positive donors to HIV-positive recipients, can only succeed if OPOs pursue referrals. However, relatively little is known about how OPO staff evaluate referrals. To better understand this process, OPO staff completed a discrete choice experiment to quantify the relative importance of seven donor characteristics on the decision to pursue a theoretical donor. Relative importance was defined by Partworth utility using a hierarchical Bayesian conditional logit model. There were 51 respondents from 36 of 58 OPOs in the United States. Of the seven attributes, organ and tissue potential were the most influential, followed by age, type of death, HIV status, donor registration, and Hepatitis C status. To be preferred to an HIV-negative donor, an HIV-positive donor needed to have the potential to donate two additional organs. These data provide insight into the preferences of OPO referral staff and may help explain the lower than expected number of HIV-positive transplants performed since the passage of the HOPE Act.