Advances and innovations in living donor liver transplant techniques, matching and surgical training: Meeting report from the living donor liver transplant consensus conference.

The practice of LDLT currently delivers limited impact in western transplant centers. The American Society of Transplantation organized a virtual consensus conference in October 2021 to identify barriers and gaps to LDLT growth, and to provide evidence-based recommendations to foster safe expansion of LDLT in the United States. This article reports the findings and recommendations regarding innovations and advances in approaches to donor-recipient matching challenges, the technical aspects of the donor and recipient operations, and surgical training. Among these themes, the barriers deemed most influential/detrimental to LDLT expansion in the United States included: (1) prohibitive issues related to donor age, graft size, insufficient donor remnant, and ABO incompatibility; (2) lack of acknowledgment and awareness of the excellent outcomes and benefits of LDLT; (3) ambiguous messaging regarding LDLT to patients and hospital leadership; and (4) a limited number of proficient LDLT surgeons across the United States. Donor-recipient mismatching may be circumvented by way of liver paired exchange. The creation of a national registry to generate granular data on donor-recipient matching will guide the practice of liver paired exchange. The surgical challenges to LDLT are addressed herein and focuses on the development of robust training pathways resulting in proficiency in donor and recipient surgery. Utilizing strong mentorship/collaboration programs with novel training practices under the auspices of established training and certification bodies will add to the breadth and depth of training.

Offer Acceptance Patterns for Liver Donors Aged 70 and Older.

Despite a documented survival benefit, older liver donor (OLD, age ≥70) graft offers are frequently declined, with utilization worsening over the last decade. To understand how offer acceptance varies by center, we studied 1113 eventually transplanted OLD grafts from 2009 to 2017 using Scientific Registry of Transplant Recipients (SRTR) data and random-intercept multilevel logistic regression. To understand how center-level acceptance of OLD graft offers might be associated with waitlist and posttransplant outcomes, we studied all adult, actively listed, liver-only candidates and recipients during the study period using Poisson regression (transplant rate), competing risks regression (waitlist mortality), and Cox regression (posttransplant mortality). Among 117 centers, OLD offer acceptance ranged from 0 (23 centers) to 95 acceptances, with a median odds ratio of 2.88. Thus, a candidate may be three times as likely to receive an OLD graft simply by listing at a different center. Centers in the highest quartile (Q4) of OLD acceptance (accepted 39% of OLD offers) accepted more nationally shared organs (Q4 versus Q1: 14.1% versus 0.0%, P < 0.001) and had higher annual liver transplant volume (Q4 versus Q1: 80 versus 21, P < 0.001). After adjustment, nationally shared OLD offers (adjusted odds ratio [aOR]: 0.16, 95% confidence interval [CI]: 0.13-0.20) and offers to centers with higher median Model for End-Stage Liver Disease (MELD) at transplant (aOR: 0.74, 95% CI: 0.62-0.87) were less likely to be accepted. OLD offers to centers with higher annual transplant volume were more likely to be accepted (aOR: 1.21, 95% CI: 1.14-1.30). Additionally, candidates listed at centers within the highest quartile of OLD graft offer acceptance had higher deceased donor liver transplantation (DDLT) rates (adjusted incidence rate ratio: 1.45, 95% CI: 1.41-1.50), lower waitlist mortality (adjusted subhazard ratio: 0.76, 95% CI: 0.72-0.76), and similar posttransplant survival (adjusted hazard ratio: 0.93, 95% CI: 0.86-1.01) when compared with those listed at centers in the lowest quartile of OLD graft offer acceptance. The wide variation in OLD offer acceptance supports the need for optimizing the organ offer process and efficiently directing OLD offers to centers more likely to use them.

Development and Validation of an Inflammatory-Frailty Index for Kidney Transplantation.

BACKGROUND: Physical frailty phenotype is characterized by decreased physiologic reserve to stressors and associated with poor outcomes, such as delirium and mortality, that may result from post-kidney transplant (KT) inflammation. Despite a hypothesized underlying pro-inflammatory state, conventional measures of frailty typically do not incorporate inflammatory biomarkers directly. Among KT candidates and recipients, we evaluated the inclusion of inflammatory biomarkers with traditional physical frailty phenotype components. METHODS: Among 1154 KT candidates and recipients with measures of physical frailty phenotype and inflammation (interleukin 6 [IL6], tumor necrosis factor alpha [TNFα], C-reactive protein [CRP]) at 2 transplant centers (2009-2017), we evaluated construct validity of inflammatory-frailty using latent class analysis. Inflammatory-frailty measures combined 5 physical frailty phenotype components plus the addition of an individual inflammatory biomarkers, separately (highest tertiles) as a sixth component. We then used Kaplan-Meier methods and adjusted Cox proportional hazards to assess post-KT mortality risk by inflammatory-frailty (n = 378); Harrell's C-statistics assessed risk prediction (discrimination). RESULTS: Based on fit criteria, a 2-class solution (frail vs nonfrail) for inflammatory-frailty was the best-fitting model. Five-year survival (frail vs nonfrail) was: 81% versus 93% (IL6-frailty), 87% versus 89% (CRP-frailty), and 83% versus 91% (TNFα-frailty). Mortality was 2.07-fold higher for IL6-frail recipients (95% CI: 1.03-4.19, p = .04); there were no associations between the mortality and the other inflammatory-frailty indices (TNFα-frail: 1.88, 95% CI: 0.95-3.74, p = .07; CRP-frail: 1.02, 95% CI: 0.52-2.03, p = .95). However, none of the frailty-inflammatory indices (all C-statistics = 0.71) improved post-KT mortality risk prediction over the physical frailty phenotype (C-statistics = 0.70). CONCLUSIONS: Measurement of IL6-frailty at transplantation can inform which patients should be targeted for pre-KT interventions. However, the traditional physical frailty phenotype is sufficient for post-KT mortality risk prediction.

Minimizing Risks of Liver Transplantation With Steatotic Donor Livers by Preferred Recipient Matching.

BACKGROUND: Donor livers with ≥30% macrosteatosis (steatotic livers) represent a possible expansion to the donor pool, but are frequently discarded as they are associated with an increased risk of mortality and graft loss. We hypothesized that there are certain recipient phenotypes that would tolerate donor steatosis well, and are therefore best suited to receive these grafts. METHODS: Using national registry data from the Scientific Registry of Transplant Recipients between 2006 and 2017, we compared 2048 liver transplant recipients of steatotic livers with 69 394 recipients of nonsteatotic (<30%) livers. We identified recipient factors that amplified the impact of donor steatosis on mortality and graft loss using interaction analysis, classifying recipients without these factors as preferred recipients. We compared mortality and graft loss with steatotic versus nonsteatotic livers in preferred and nonpreferred recipients using Cox regression. RESULTS: Preferred recipients of steatotic livers were determined to be first-time recipients with a model for end-stage liver disease 15-34, without primary biliary cirrhosis, and not on life support before transplant. Preferred recipients had no increased mortality risk (hazard ratio [HR]: 0.921.041.16; P = 0.5) or graft loss (HR: 0.931.031.15; P = 0.5) with steatotic versus nonsteatotic livers. Conversely, nonpreferred recipients had a 41% increased mortality risk (HR: 1.171.411.70; P < 0.001) and 39% increased risk of graft loss (HR: 1.161.391.66; P < 0.001) with steatotic versus nonsteatotic livers. CONCLUSIONS: The risks of liver transplantation with steatotic donor livers could be minimized by appropriate recipient matching.

Outcomes After Declining a Steatotic Donor Liver for Liver Transplant Candidates in the United States.

BACKGROUND: Steatotic donor livers (SDLs, ≥30% macrosteatosis on biopsy) are often declined, as they are associated with a higher risk of graft loss, even though candidates may wait an indefinite time for a subsequent organ offer. We sought to quantify outcomes for transplant candidates who declined or accepted an SDL offer. METHODS: We used Scientific Registry of Transplant Recipients offer data from 2009 to 2015 to compare outcomes of 759 candidates who accepted an SDL to 13 362 matched controls who declined and followed candidates from the date of decision (decline or accept) until death or end of study period. We used a competing risk framework to understand the natural history of candidates who declined and Cox regression to compare postdecision survival after declining versus accepting (ie, what could have happened if candidates who declined had instead accepted). RESULTS: Among those who declined an SDL, only 53.1% of candidates were subsequently transplanted, 23.8% died, and 19.4% were removed from the waitlist. Candidates who accepted had a brief perioperative risk period within the first month posttransplant (adjusted hazard ratio [aHR]: 2.493.494.89, P < 0.001), but a 62% lower mortality risk (aHR: 0.310.380.46, P < 0.001) beyond this. Although the long-term survival benefit of acceptance did not vary by candidate model for end-stage liver disease (MELD), the short-term risk period did. MELD 6-21 candidates who accepted an SDL had a 7.88-fold higher mortality risk (aHR: 4.807.8812.93, P < 0.001) in the first month posttransplant, whereas MELD 35-40 candidates had a 68% lower mortality risk (aHR: 0.110.320.90, P = 0.03). CONCLUSIONS: Appropriately selected SDLs can decrease wait time and provide substantial long-term survival benefit for liver transplant candidates.

Poor Outcomes in Kidney Transplant Candidates and Recipients With History of Falls.

BACKGROUND: Falls occur in 28% of hemodialysis patients and increase the risk of physical impairment, morbidity, and mortality. Therefore, it is likely that kidney transplantation (KT) candidates with recurrent falls are less likely to access KT and more likely to experience adverse post-KT outcomes. METHODS: We used a 2-center cohort study of KT candidates (n = 3666) and recipients (n = 770) (January 2009 to January 2018). Among candidates, we estimated time to listing, waitlist mortality, and transplant rate by recurrent falls (≥2 falls) before evaluation using adjusted regression. Among KT recipients, we estimated risk of mortality, graft loss, and length of stay by recurrent falls before KT using adjusted regression. RESULTS: Candidates with recurrent falls (6.5%) had a lower chance of listing (adjusted hazard ratio [aHR] = 0.68, 95% confidence interval [CI], 0.56-0.83) but not transplant rate; waitlist mortality was 31-fold (95% CI, 11.33-85.93) higher in the first year and gradually decreased over time. Recipients with recurrent falls (5.1%) were at increased risk of mortality (aHR = 51.43, 95% CI, 16.00-165.43) and graft loss (aHR = 33.57, 95% CI, 11.25-100.21) in the first year, which declined over time, and a longer length of stay (adjusted relative ratio [aRR] = 1.13, 95% CI, 1.03-1.25). In summary, 6.5% of KT candidates and 5.1% of recipients experienced recurrent falls which were associated with adverse pre- and post-KT outcomes. CONCLUSIONS: While recurrent falls were relatively rare in KT candidates and recipients, they were associated with adverse outcomes. Transplant centers should consider employing fall prevention strategies for high-risk candidates as part of comprehensive prehabilitation.

Association of Socioeconomic Status and Comorbidities with Racial Disparities during Kidney Transplant Evaluation.

BACKGROUND AND OBJECTIVES: Black patients referred for kidney transplantation have surpassed many obstacles but likely face continued racial disparities before transplant. The mechanisms that underlie these disparities are unclear. We determined the contributions of socioeconomic status (SES) and comorbidities as mediators to disparities in listing and transplant. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied a cohort (n=1452 black; n=1561 white) of patients with kidney failure who were referred for and started the transplant process (2009-2018). We estimated the direct and indirect effects of SES (self-reported income, education, and employment) and medical comorbidities (self-reported and chart-abstracted) as mediators of racial disparities in listing using Cox proportional hazards analysis with inverse odds ratio weighting. Among the 983 black and 1085 white candidates actively listed, we estimated the direct and indirect effects of SES and comorbidities as mediators of racial disparities on receipt of transplant using Poisson regression with inverse odds ratio weighting. RESULTS: Within the first year, 876 (60%) black and 1028 (66%) white patients were waitlisted. The relative risk of listing for black compared with white patients was 0.76 (95% confidence interval [95% CI], 0.69 to 0.83); after adjustment for SES and comorbidity, the relative risk was 0.90 (95% CI, 0.83 to 0.97). The proportion of the racial disparity in listing was explained by SES by 36% (95% CI, 26% to 57%), comorbidity by 44% (95% CI, 35% to 61%), and SES with comorbidity by 58% (95% CI, 44% to 85%). There were 409 (42%) black and 496 (45%) white listed candidates transplanted, with a median duration of follow-up of 3.9 (interquartile range, 1.2-7.1) and 2.8 (interquartile range, 0.8-6.3) years, respectively. The incidence rate ratio for black versus white candidates was 0.87 (95% CI, 0.79 to 0.96); SES and comorbidity did not explain the racial disparity. CONCLUSIONS: SES and comorbidity partially mediated racial disparities in listing but not for transplant.

Changes in frailty are associated with waitlist mortality in patients with cirrhosis.

BACKGROUND & AIMS: To date, studies evaluating the association between frailty and mortality in patients with cirrhosis have been limited to assessments of frailty at a single time point. We aimed to evaluate changes in frailty over time and their association with death/delisting in patients too sick for liver transplantation. METHODS: Adults with cirrhosis, listed for liver transplantation at 8 US centers, underwent ambulatory longitudinal frailty testing using the liver frailty index (LFI). We used multilevel linear mixed-effects regression to model and predict changes in LFI (ΔLFI) per 3 months, based on age, gender, model for end-stage liver disease (MELD)-Na, ascites, and hepatic encephalopathy, categorizing patients by frailty trajectories. Competing risk regression evaluated the subhazard ratio (sHR) of baseline LFI and predicted ΔLFI on death/delisting, with transplantation as the competing risk. RESULTS: We analyzed 2,851 visits from 1,093 outpatients with cirrhosis. Patients with severe worsening of frailty had worse baseline LFI and were more likely to have non-alcoholic fatty liver disease, diabetes, or dialysis-dependence. After a median follow-up of 11 months, 223 (20%) of the overall cohort died/were delisted because of sickness. The cumulative incidence of death/delisting increased by worsening ΔLFI group. In competing risk regression adjusted for baseline LFI, age, height, MELD-Na, and albumin, a 0.1 unit change in ΔLFI per 3 months was associated with a 2.04-fold increased risk of death/delisting (95% CI 1.35-3.09). CONCLUSION: Worsening frailty was significantly associated with death/delisting independent of baseline frailty and MELD-Na. Notably, patients who experienced improvements in frailty had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty, using the LFI, in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty. LAY SUMMARY: Frailty, as measured at a single time point, is predictive of death in patients with cirrhosis, but whether changes in frailty over time are associated with death is unknown. In a study of over 1,000 patients with cirrhosis who underwent frailty testing, we demonstrate that worsening frailty is strongly linked with mortality, regardless of baseline frailty and liver disease severity. Notably, patients who experienced improvements in frailty over time had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.

Association Between Living Kidney Donor Postdonation Hypertension and Recipient Graft Failure.

BACKGROUND: Recipients of kidneys from living donors who subsequently develop end-stage renal disease (ESRD) also have higher graft failure, suggesting the 2 donor kidneys share risk factors that could inform recipient outcomes. Given that donor ESRD is rare, an earlier and more common postdonation outcome could serve as a surrogate to individualize counseling and management for recipients. Hypertension is a frequent event before donor ESRD; thus, early postdonation hypertension might indicate higher risk of graft failure. METHODS: We studied Scientific Registry of Transplant Recipients data to quantify the association between early postdonation hypertension and recipient graft failure using propensity score-weighted Cox proportional hazards regression. We also examined the association between postdonation systolic blood pressure and graft failure. RESULTS: Of 37 901 recipients, 2.4% had a donor who developed hypertension within 2 years postdonation. Controlling for donor and recipient characteristics, recipients whose donors developed hypertension had no higher risk for graft failure (adjusted hazard ratio [aHR] 1.03, 95% confidence interval [CI] 0.85-1.25, P = 0.72). This was consistent among subgroups of recipients at higher risk for adverse outcomes due to hyperfiltration: African American recipients (aHR 1.10, 95% CI 0.70-1.73, P = 0.68) and those with ESRD caused by hypertension (aHR 1.10, 95% CI 0.65-1.85, P = 0.73) or diabetes (aHR 0.80, 95% CI 0.56-1.13, P = 0.20). However, graft failure was associated with postdonation systolic blood pressure (per 10 mm Hg, aHR 1.05, 95% CI 1.03-1.08, P < 0.001). CONCLUSIONS: Although postdonation systolic blood pressure is associated with graft failure, the reported diagnosis of hypertension as determined by the requirement for blood pressure treatment early postdonation did not portend a higher risk of recipient graft failure in the same way as eventual postdonation ESRD.

Cognitive Function, Access to Kidney Transplantation, and Waitlist Mortality Among Kidney Transplant Candidates With or Without Diabetes.

RATIONALE & OBJECTIVE: Intact cognition is generally a prerequisite for navigating through and completing evaluation for kidney transplantation. Despite kidney transplantation being contraindicated for those with severe dementia, screening for more mild forms of cognitive impairment before referral is rare. Candidates may have unrecognized cognitive impairment, which may prolong evaluation, elevate mortality risk, and hinder access to kidney transplantation. We estimated the burden of cognitive impairment and its association with access to kidney transplantation and waitlist mortality. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,630 participants (January 2009 to June 2018) with cognitive function measured (by the Modified Mini-Mental State Examination [3MS]) at kidney transplantation evaluation at 1 of 2 transplantation centers. PREDICTORS: Cognitive impairment (3MS score<80). OUTCOMES: Listing, waitlist mortality, and kidney transplantation. ANALYTICAL APPROACH: We estimated the adjusted chance of listing (Cox regression), risk for waitlist mortality (competing-risks regression), and kidney transplantation rate (Poisson regression) by cognitive impairment. Given potential differences in cause of cognitive impairment among those with and without diabetes, we tested whether these associations differed by diabetes status using a Wald test. RESULTS: At evaluation, 6.4% of participants had cognitive impairment, which was independently associated with 25% lower chance of listing (adjusted HR, 0.75; 95% CI, 0.61-0.91); this association did not differ by diabetes status (Pinteraction=0.07). There was a nominal difference by diabetes status for the association between cognitive impairment and kidney transplantation rate (Pinteraction=0.05), while the association between cognitive impairment and waitlist mortality differed by diabetes status kidney transplantation rates (Pinteraction=0.02). Among candidates without diabetes, those with cognitive impairment were at 2.47 (95% CI, 1.31-4.66) times greater risk for waitlist mortality; cognitive impairment was not associated with this outcome among candidates with diabetes. LIMITATIONS: Single measure of cognitive impairment. CONCLUSIONS: Cognitive impairment is associated with a lower chance of being placed on the waitlist, and among patients without diabetes, with increased mortality on the waitlist. Future studies should investigate whether implementation of screening for cognitive impairment improves these outcomes.

Perceptions, Barriers, and Experiences With Successful Aging Before and After Kidney Transplantation: A Focus Group Study.

BACKGROUND: End-stage kidney disease (ESKD) patients are living longer, often into older age, and commonly pursue kidney transplantation. Successful aging, a multidimensional construct of physical and social wellbeing, has been expanded and adapted for patients with chronic disease. However, perceptions of, barriers to, and experiences with successful aging among adults with ESKD are unclear and likely differ based on whether they have received a kidney transplant. METHODS: Ten focus groups were held with 39 total ESKD patients aged ≥50 years (19 transplant candidates, 20 transplant recipients). Transcriptions were analyzed thematically by 2 independent coders using an inductive, constant comparative approach. RESULTS: The mean age was 64.8 (SD = 7.5); 51% were African American and 64% were males. Six themes were identified: familiarity with successful aging, perceptions of successful aging after ESKD diagnosis, barriers to successful aging, experiences with successful aging among transplant candidates, experiences with successful aging among transplant recipients, and suggested interventions. While all participants sought to achieve successful aging while living with ESKD, experiences with successful aging differed between candidates and recipients. Candidates struggled with the limitations of dialysis; some viewed transplantation as an opportunity to age successfully, while others were resigned to the drawbacks of dialysis. In contrast, transplant recipients were optimistic about their ability to age successfully, believing their transplant facilitated successful aging. Participants believed support groups for adults with ESKD and more thoughtful health care for aging adults would promote successful aging. CONCLUSIONS: Adults with ESKD may benefit from discussions with their clinicians and caregivers about goals, barriers, and strategies regarding successful aging.

Physical Impairment and Access to Kidney Transplantation.

BACKGROUND: The short physical performance battery (SPPB) test is an objective measurement of lower extremity function (walk speed, balance, chair stands). SPPB impairment is associated with longer length of stay and increased mortality in kidney transplant (KT) recipients. Furthermore, the SPPB test may represent an objective quantification of the "foot of the bed test" utilized by clinicians; therefore, impairment may translate with decreased access to KT. METHODS: We studied 3255 participants (2009-2018) at 2 KT centers. SPPB impairment was defined as a score of ≤10. We estimated time to listing, waitlist mortality, and transplant rate by SPPB impairment status using Cox proportional hazards, competing risks, and Poisson regression. RESULTS: The mean age was 54 years (SD = 14; range 18-89) and 54% had SPPB impairment. Impaired participants were less likely to be listed for KT (adjusted hazard ratio: 0.70, 95% CI: 0.64-0.77, P < 0.001). Also, once listed, impaired candidates had a 1.6-fold increased risk of waitlist mortality (adjusted subhazard ratio: 1.56, 95% CI: 1.18-2.06, P = 0.002). Furthermore, impaired candidates were transplanted 16% less frequently (adjusted incidence rate ratio: 0.84, 95% CI: 0.73-0.98, P = 0.02). CONCLUSIONS: SPPB impairment was highly prevalent in KT candidates. Impaired candidates had decreased chance of listing, increased risk of waitlist mortality, and decreased rate of KT. Identification of robust KT candidates and improvement in lower extremity function are potential ways to improve survival on the waitlist and access to KT.

Delayed Graft Function in Simultaneous Liver Kidney Transplantation.

BACKGROUND: Delayed graft function (DGF) is associated with inferior posttransplant outcomes in kidney transplantation. Given these adverse outcomes, we sought to determine the incidence, unique risk factors, and posttransplant outcomes for simultaneous liver kidney (SLK) transplant recipients developing DGF. METHODS: We studied 6214 adult SLK recipients from March 2002 to February 2017 using the Scientific Registry of Transplant Recipients. We determined associations between risk factors and DGF using Poisson multivariate regression and between DGF and graft failure and mortality using Cox proportional hazard analysis. RESULTS: The overall rate of DGF was 21.8%. Risk factors for DGF in the hepatitis C virus (HCV)-negative recipient population included pretransplant dialysis (adjusted incident rate ratio [aIRR] 3.26, P = 0.004), donor body mass index (aIRR 1.25 per 5 kg/m, P = 0.01), and transplantation with a donation after circulatory death (aIRR 5.38, P = 0.001) or imported donor organ (regional share aIRR 1.69, P = 0.03; national share aIRR 4.82, P < 0.001). DGF was associated with a 2.6-fold increase in kidney graft failure (adjusted hazard ratio [aHR] 2.63, P < 0.001), 1.6-fold increase in liver graft failure (aHR 1.62, P < 0.001), and 1.6-fold increase in mortality (aHR 1.62, P < 0.001). CONCLUSIONS: In HCV-negative SLK recipients, recipient pretransplant dialysis and components of kidney graft quality comprise significant risk factors for DGF. Regardless of HCV status, DGF is associated with inferior posttransplant outcomes. Understanding these risk factors during clinical decision-making may improve prevention of DGF and may represent an opportunity to improve posttransplant outcomes.

Kidney transplant outcomes in recipients with visual, hearing, physical and walking impairments: a prospective cohort study.

BACKGROUND: Disability in general has been associated with poor outcomes in kidney transplant (KT) recipients. However, disability can be derived from various components, specifically visual, hearing, physical and walking impairments. Different impairments may compromise the patient through different mechanisms and might impact different aspects of KT outcomes. METHODS: In our prospective cohort study (June 2013-June 2017), 465 recipients reported hearing, visual, physical and walking impairments before KT. We used hybrid registry-augmented Cox regression, adjusting for confounders using the US KT population (Scientific Registry of Transplant Recipients, N = 66 891), to assess the independent association between impairments and post-KT outcomes [death-censored graft failure (DCGF) and mortality]. RESULTS: In our cohort of 465 recipients, 31.6% reported one or more impairments (hearing 9.3%, visual 16.6%, physical 9.1%, walking 12.1%). Visual impairment was associated with a 3.36-fold [95% confidence interval (CI) 1.17-9.65] higher DCGF risk, however, hearing [2.77 (95% CI 0.78-9.82)], physical [0.67 (95% CI 0.08-3.35)] and walking [0.50 (95% CI 0.06-3.89)] impairments were not. Walking impairment was associated with a 3.13-fold (95% CI 1.32-7.48) higher mortality risk, however, visual [1.20 (95% CI 0.48-2.98)], hearing [1.01 (95% CI 0.29-3.47)] and physical [1.16 (95% CI 0.34-3.94)] impairments were not. CONCLUSIONS: Impairments are common among KT recipients, yet only visual impairment and walking impairment are associated with adverse post-KT outcomes. Referring nephrologists and KT centers should identify recipients with visual and walking impairments who might benefit from targeted interventions pre-KT, additional supportive care and close post-KT monitoring.

Multicenter Study of Age, Frailty, and Waitlist Mortality Among Liver Transplant Candidates.

OBJECTIVE: To determine if the association of frailty and waitlist mortality varies by candidate age. BACKGROUND: Frailty, a construct developed in geriatrics, is a state of decreased physiologic reserve, and is associated with mortality while awaiting liver transplantation (LT). However, older candidates have high comorbidity burden and less physiologic reserve, so the relationship between frailty and waitlist mortality may vary by candidate age. METHODS: We studied adults listed for LT at 2 transplant centers. The liver frailty index (grip strength, chair stands, balance) was measured at evaluation, with frailty defined as liver frailty index  ≥ 4.5. We compared the prevalence of frailty in older (≥65 yr) and younger (18-64 yr) candidates. We studied the association between frailty, age, interaction between the 2, and waitlist mortality using competing risks regression adjusted for sex, BMI, and MELDNa. RESULTS: Among 882 LT candidates, 16.6% were ≥ 65 years. Older candidates were more likely to be frail (33.3% vs 21.7%, P = 0.002). Older age [adjusted subhazard ratio (aSHR): 2.16, 95% CI: 1.51-3.09, P < 0.001] and frailty (aSHR: 1.92, 95% CI: 1.38-2.67, P < 0.001) were independently associated with higher risk of waitlist mortality. However, the association between waitlist mortality and frailty did not vary by candidate age (aSHR of frailty for younger patients: 1.90, 95% CI: 1.28-2.80, P = 0.001; aSHR of frailty for older patients: 1.98, 95% CI: 1.07-3.67, P = 0.03; P interaction = 0.9). CONCLUSIONS: Older candidates experienced higher rates of frailty than younger candidates. However, regardless of age, frailty was associated with nearly 2-fold increased risk of waitlist mortality. Our data support the applicability of the frailty concept to the whole LT population and can guide the development of prehabilitation programs targeting frailty in LT patients of all ages.

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 2005-2007:13.15 15.2817.74 ; 2008-2011:11.77 13.4115.29 ; 2012-2014:9.87 11.3713.10 ; 2015-2017:7.79 8.8910.15 , 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]: 0.43 0.540.68 , P < .001) and 47% lower risk of graft loss (aHR: 0.42 0.530.67 , P < .001) compared to 2005 to 2011. In fact, in 2012 to 2017, recipients of SDLs had equivalent mortality (aHR: 0.90 1.041.21 , P = .6) and graft loss (aHR: 0.90 1.041.20 , P = .6) to recipients of non-SDLs. Increasing utilization of SDLs might be a reasonable strategy to expand the donor pool.

Functional independence, access to kidney transplantation and waitlist mortality.

BACKGROUND: Approximately half of the patients who progress to end-stage kidney disease (ESKD) and undergo dialysis develop difficulties carrying out essential self-care activities, leading to institutionalization and mortality. It is unclear what percentage of kidney transplant (KT) candidates, a group of ESKD patients selected to be healthy enough to withstand transplantation, are functionally independent and whether independence is associated with better access to KT and reduced waitlist mortality. METHODS: We studied a prospective cohort of 3168 ESKD participants (January 2009 to June 2018) who self-reported functional independence in more basic self-care Activities of Daily Living (ADL) (needing help with eating, dressing, walking, grooming, toileting and bathing) and more complex instrumental ADL (IADL) (needing help using a phone, shopping, cooking, housework, washing, using transportation, managing medications and managing money). We estimated adjusted associations between functional independence (separately) and listing (Cox), waitlist mortality (competing risks) and transplant rates (Poisson). RESULTS: At KT evaluation, 92.4% were independent in ADLs, but only 68.5% were independent in IADLs. Functionally independent participants had a higher chance of listing for KT [ADL: adjusted hazard ratio (aHR) = 1.55, 95% confidence interval (CI) 1.30-1.87; IADL: aHR = 1.39, 95% CI 1.26-1.52]. Among KT candidates, ADL independence was associated with lower waitlist mortality risk [adjusted subdistribution HR (aSHR) = 0.66, 95% CI 0.44-0.98] and higher rate of KT [adjusted incidence rate ratio (aIRR) = 1.58, 95% CI 1.12-2.22]; the same was not observed for IADL independence (aSHR = 0.86, 95% CI 0.65-1.12; aIRR = 1.01, 95% CI 0.97-1.19). CONCLUSIONS: Functional independence in more basic self-care ADL was associated with better KT access and lower waitlist mortality. Nephrologists, geriatricians and transplant surgeons should screen KT candidates for ADLs, and identify interventions to promote independence and improve waitlist outcomes.

Prevalence of frailty among kidney transplant candidates and recipients in the United States: Estimates from a National Registry and Multicenter Cohort Study.

Frailty, a measure of physiologic reserve, is associated with poor outcomes and mortality among kidney transplant (KT) candidates and recipients. There are no national estimates of frailty in this population, which may help patient counseling and resource allocation at transplant centers. We studied 4616 KT candidates and 1763 recipients in our multicenter prospective cohort of frailty from 2008-2018 with Fried frailty measurements. Using Scientific Registry of Transplant Recipients (SRTR) data (KT candidates = 560 143 and recipients = 243 508), we projected the national prevalence of frailty (for KT candidates and recipients separately) using standardization through inverse probability weighting, accounting for candidate/recipient, donor, and transplant factors. In our multicenter cohort, 13.3% of KT candidates were frail at evaluation; 8.2% of LDKT recipients and 17.8% of DDKT recipients were frail at transplantation. Projected nationally, our modeling strategy estimated 91 738 KT candidates or 16.4% (95% confidence interval [CI] 14.4%-18.4%) of all KT candidates during the study period were frail, and that 34 822 KT recipients or 14.3% (95% CI 12.3%-16.3%) of all KT recipients were frail (LDKT = 8.2%; DDKT = 17.8%). Given the estimated national prevalence of frailty, transplant programs should consider assessing the condition during KT evaluation to improve patient counseling and resource allocation along with identification of recipients at risk for poor outcomes.

Early Liver Transplantation in Acute Alcoholic Hepatitis.

Alcohol-related liver disease (ALD) is currently the leading indication for liver transplantation in the United States. Among patients with ALD, those with acute alcoholic hepatitis who do not respond to medical treatment have a 6-month mortality of 70% without transplantation. Despite the high mortality, the majority of patients will not be eligible for transplant, given that most centers follow the 6-month abstinence rule. A handful of centers in Europe and the United States perform early liver transplantation (< 6 months abstinence) in these patients, as it provides a substantial survival benefit. Short-term outcomes for these recipients are favorable, and relapse rates parallel those seen in alcoholic cirrhosis transplant recipients who have completed the 6-month wait period. Moving forward, studies examining long-term outcomes and candidate selection are necessary for this growing subset of liver transplant candidates.