Faculty Bibliography

BACKGROUND & AIMS:Frailty is associated with mortality in patients with cirrhosis. We measured frailty using 3 simple tests and calculated Liver Frailty Index (LFI) scores for patients at multiple ambulatory centers. We investigated associations between LFI scores, ascites, and hepatic encephalopathy (HE) and mortality. METHODS:Adults without hepatocellular carcinoma who were on the liver transplantation waitlist at 9 centers in the United States (N = 1044) were evaluated using the LFI; LFI scores of at least 4.5 indicated that patients were frail. We performed logistic regression analyses to assess associations between frailty and ascites or HE and competing risk regression analyses (with liver transplantation as the competing risk) to estimate sub-hazard ratios (sHRs) of waitlist mortality (death or removal from the waitlist). RESULTS:Of study subjects, 36% had ascites, 41% had HE, and 25% were frail. The odds of frailty were higher for patients with ascites (adjusted odd ratio 1.56, 95% confidence interval [CI] 1.15-2.14) or HE (odd ratio 2.45, 95% CI 1.80-3.33) than for those without these features. Larger proportions of frail patients with ascites (29%) or HE (30%) died while on the waitlist compared with patients who were not frail (17% of patients with ascites and 20% with HE). In univariable analysis, ascites (sHR 1.52, 95% CI 1.14-2.05), HE (sHR 1.84, 95% CI 1.38-2.45), and frailty (sHR 2.38, 95% CI 1.77-3.20) were associated with waitlist mortality. In adjusted models, only frailty remained significantly associated with waitlist mortality (sHR 1.82, 95% CI 1.31-2.52); ascites and HE were not. CONCLUSIONS:Frailty is a prevalent complication of cirrhosis that is observed more frequently in patients with ascites or HE and independently associated with waitlist mortality. LFI scores can be used to objectively quantify risk of death related to frailty-in excess of liver disease severity-in patients with cirrhosis.

BACKGROUND:Restoration of kidney function after kidney transplant generally improves cognitive function. It is unclear whether frail recipients, with higher susceptibility to surgical stressors, achieve such post-transplant cognitive improvements or whether they experience subsequent cognitive decline as they age with a functioning graft. METHODS:In this two-center cohort study, we assessed pretransplant frailty (Fried physical frailty phenotype) and cognitive function (Modified Mini-Mental State Examination) in adult kidney transplant recipients. To investigate potential short- and medium-term effects of frailty on post-transplant cognitive trajectories, we measured cognitive function up to 4 years post-transplant. Using an adjusted mixed effects model with a random slope (time) and intercept (person), we characterized post-transplant cognitive trajectories by pretransplant frailty, accounting for nonlinear trajectories. RESULTS:Of 665 recipients (mean age 52.0 years) followed for a median of 1.5 years, 15.0% were frail. After adjustment, pretransplant cognitive scores were significantly lower among frail patients compared with nonfrail patients (89.0 versus 90.8 points). By 3 months post-transplant, cognitive performance improved for both frail (slope =0.22 points per week) and nonfrail (slope =0.14 points per week) recipients. Between 1 and 4 years post-transplant, improvements plateaued among nonfrail recipients (slope =0.005 points per week), whereas cognitive function declined among frail recipients (slope =-0.04 points per week). At 4 years post-transplant, cognitive scores were 5.8 points lower for frail recipients compared with nonfrail recipients. CONCLUSIONS:On average, both frail and nonfrail recipients experience short-term cognitive improvement post-transplant. However, frailty is associated with medium-term cognitive decline post-transplant. Interventions to prevent cognitive decline among frail recipients should be identified.

BACKGROUND:Cannabis is categorized as an illicit drug in most US states, but legalization for medical indications is increasing. Policies and guidance on cannabis use in transplant patients remain controversial. METHODS:We examined a database linking national kidney transplant records (n = 52 689) with Medicare claims to identify diagnoses of cannabis dependence or abuse (CDOA) and associations [adjusted hazard ratio (aHR) with 95% upper and lower confidence limits (CLs)] with graft, patient, and other clinical outcomes. RESULTS:CDOA was diagnosed in only 0.5% (n = 254) and 0.3% (n = 163) of kidney transplant recipients in the years before and after transplant, respectively. Patients with pretransplant CDOA were more likely to be 19 to 30 years of age and of black race, and less likely to be obese, college-educated, and employed. After multivariate and propensity adjustment, CDOA in the year before transplant was not associated with death or graft failure in the year after transplant, but was associated with posttransplant psychosocial problems such as alcohol abuse, other drug abuse, noncompliance, schizophrenia, and depression. Furthermore, CDOA in the first year posttransplant was associated with an approximately 2-fold increased risk of death-censored graft failure (aHR, 2.29; 95% CL, 1.59-3.32), all-cause graft loss (aHR, 2.09; 95% CL, 1.50-2.91), and death (aHR, 1.79; 95% CL, 1.06-3.04) in the subsequent 2 years. Posttransplant CDOA was also associated with cardiovascular, pulmonary, and psychosocial problems, and with events such as accidents and fractures. CONCLUSIONS:Although associations likely, in part, reflect associated conditions or behaviors, clinical diagnosis of CDOA in the year after transplant appears to have prognostic implications for allograft and patient outcomes. Recipients with posttransplant CDOA warrant focused monitoring and support.

BACKGROUND:Recipients of nonkidney solid organ transplants (nkSOT) are living longer, and 11%-18% will develop end stage renal disease (ESRD). While our general inclination is to treat nkSOT recipients who develop ESRD with a kidney transplant (KT), an increasing number are developing ESRD at an older age where KT may not be the most appropriate treatment. It is possible that the risk of older age and prior nkSOT might synergize to make KT too risky, but this has never been explored. METHODS:To examine death-censored graft loss and mortality for KT recipients with and without prior nkSOT, we used Scientific Registry of Transplant Recipients data to identify 42 089 older (age ≥65) KT recipients between 1995 and 2016. Additionally, to better understand treatment options for these patients and survival benefit of KT, we identified 5023 older (age ≥65) with prior nkSOT recipients listed for subsequent KT, of whom 863 received transplants. RESULTS:Compared with 41 159 older KT recipients without prior nkSOT, death-censored graft loss was similar (adjusted hazard ratio [aHR]: 1.13, 95% CI: 0.93-1.37, P = 0.2), but mortality (aHR: 1.40, 95% CI: 1.28-1.54, P < 0.001) was greater for older KT recipients with prior nkSOT. Nonetheless, in a survival benefit model (survival with versus without the transplant), among older prior nkSOT recipients, KT decreased the risk of mortality by more than half (aHR: 0.47, 95% CI: 0.42-0.54, P < 0.001). CONCLUSIONS:Older prior nkSOT recipients who subsequently develop ESRD derive survival benefit from KT, but graft longevity is limited by overall survival in this population. These findings can help guide patient counseling for this challenging population.

Recent OPTN proposals to address geographic disparity in liver allocation have involved circular boundaries: the policy selected 12/17 allocated to 150-mile circles in addition to DSAs/regions, and the policy selected 12/18 allocated to 150-mile circles eliminating DSA/region boundaries. However, methods to reduce geographic disparity remain controversial, within the OPTN and the transplant community. To inform ongoing discussions, we studied center-level supply/demand ratios using SRTR data (07/2013-06/2017) for 27 334 transplanted deceased donor livers and 44 652 incident waitlist candidates. Supply was the number of donors from an allocation unit (DSA or circle), allocated proportionally (by waitlist size) to the centers drawing on these donors. We measured geographic disparity as variance in log-transformed supply/demand ratio, comparing allocation based on DSAs, fixed-distance circles (150- or 400-mile radius), and fixed-population (12- or 50-million) circles. The recently proposed 150-mile radius circles (variance = 0.11, P = .9) or 12-million-population circles (variance = 0.08, P = .1) did not reduce the geographic disparity compared to DSA-based allocation (variance = 0.11). However, geographic disparity decreased substantially to 0.02 in both larger fixed-distance (400-mile, P < .001) and larger fixed-population (50-million, P < .001) circles (P = .9 comparing fixed distance and fixed population). For allocation circles to reduce geographic disparities, they must be larger than a 150-mile radius; additionally, fixed-population circles are not superior to fixed-distance circles.

Importance:In light of the growing population of older adults in the United States, older donors (aged ≥70 years) represent an expansion of the donor pool; however, their organs are underused. Liver grafts from older donors were historically associated with poor outcomes and higher discard rates, but clinical protocols, organ allocation, and the donor pool have changed in the past 15 years. Objective:To evaluate trends in demographics, discard rates, and outcomes among older liver donors and transplant recipients of livers from older donors in a large national cohort. Design, Setting, and Participants:Prospective cohort study of 4127 liver grafts from older donors and 3350 liver-only recipients of older donor grafts and 78 990 liver grafts from younger donors (aged 18-69 years) and 64 907 liver-only recipients of younger donor grafts between January 1, 2003, and December 31, 2016, in the United States. The Scientific Registry of Transplant Recipients, which includes data on all transplant recipients in the United States that are submitted by members of the Organ Procurement and Transplantation Network, was used. Exposures:Year of liver transplant and age of liver donor. Main Outcomes and Measures:Odds of graft discard and posttransplant outcomes of all-cause graft loss and mortality. Results:In this study, 4127 liver grafts from older donors were recovered for liver transplant across the study period (2003-2016); 747 liver grafts from older donors were discarded, and 3350 liver grafts from older donors were used for liver-only recipients. After adjusting for donor characteristics other than age and accounting for Organ Procurement Organization-level variation, liver grafts from older donors were more likely to be discarded compared with liver grafts from younger donors in 2003-2006 (adjusted odds ratio [aOR], 1.97; 95% CI, 1.68-2.31), 2007-2009 (aOR, 2.55; 95% CI, 2.17-3.01), 2010-2013 (aOR, 2.04; 95% CI, 1.68-2.46), and 2013-2016 (aOR, 2.37; 95% CI, 1.96-2.86) (P < .001 for all). Transplants of liver grafts from older donors represented a progressively lower proportion of all adult liver transplants, from 6.0% (n = 258 recipients) in 2003 to 3.2% (n = 211 recipients) in 2016 (P = .001). However, outcomes in recipients of grafts from older donors improved over time, with 40% lower graft loss risk (adjusted hazard ratio, 0.60; 95% CI, 0.53-0.68; P < .001) and 41% lower mortality risk (adjusted hazard ratio, 0.59; 95% CI, 0.52-0.68; P < .001) in 2010 through 2016 vs 2003 through 2009; these results were beyond the general temporal improvements in graft loss (interaction P = .03) and mortality risk (interaction P = .04) among recipients of liver grafts from younger donors. Conclusions and Relevance:These findings show that from 2003 to 2016, liver graft loss and mortality among recipients of liver grafts from older donors improved; however, liver graft discard from older donors remained increased and the number of transplants performed with liver grafts from older donors decreased. Expansion of the donor pool through broader use of liver grafts from older donors might be reasonable.

BACKGROUND:There is concern that the metrics currently used to regulate transplant centers, one-year patient and graft survival, may have adverse consequences including decreasing higher risk donor organ acceptance and transplant volume. This raises questions about whether alternative measures would be more appropriate. METHODS:We surveyed American Society of Transplant Surgeons (ASTS) and American Society of Transplantation (AST) members (n = 270) to characterize perceptions of several metrics that are used for regulation, are publicly reported, or have been suggested elsewhere, regarding their effectiveness, amenability to risk adjustment, and predicted effects on volume, mortality, and waitlist size. RESULTS:Respondents rated one-year patient and graft survival the most effective measure of quality of care (mean scores = 7.44, 7.31, respectively, out of 10) and most amenable to risk adjustment (mean scores = 6.26, 6.13, respectively). Most respondents believed alternative metrics would not impact their center's volume, waitlist size, or one-year transplant mortality. However, some did predict unintended consequences; for example, some believed using one-year waitlist mortality, one-year mortality of patients listed, or one-year mortality of patients referred for transplant would decrease the number of transplants performed (48.6%, 46.7%, and 48.3% of respondents, respectively). DISCUSSION:Despite previously published concerns with existing regulatory metrics, most participants did not believe any metrics would outperform one-year patient and graft survival.

BACKGROUND:Kidneys from infectious risk donors (IRD) confer substantial survival benefit in adults, yet the benefit of IRD kidneys to pediatric candidates remains unclear in the context of high waitlist prioritization. METHODS:Using 2010-2016 Scientific Registry of Transplant Recipients data, we studied 2417 pediatric candidates (age <18 y) who were offered an IRD kidney that was eventually used for transplantation. We followed candidates from the date of first IRD kidney offer until the date of death or censorship and used Cox regression to estimate mortality risk associated with IRD kidney acceptance versus decline, adjusting for age, sex, race, diagnosis, and dialysis time. RESULTS:Over the study period, 2250 (93.1%) pediatric candidates declined and 286 (11.8%) accepted an IRD kidney offer; 119 (41.6%) of the 286 had previously declined a different IRD kidney. Cumulative survival among those who accepted versus declined the IRD kidney was 99.6% versus 99.4% and 96.3% versus 97.8% 1 and 6 years post decision, respectively (P = 0.1). Unlike the substantial survival benefit seen in adults (hazard ratio = 0.52), among pediatric candidates, we did not detect a survival benefit associated with accepting an IRD kidney (adjusted hazard ratio: 0.791.723.73, P = 0.2). However, those who declined IRD kidneys waited a median 9.6 months for a non-IRD kidney transplant (11.2 mo among those <6 y, 8.8 mo among those on dialysis). Kidney donor profile index (KDPI) of the eventually accepted non-IRD kidneys (median = 13, interquartile range = 6-23) was similar to KDPI of the declined IRD kidneys (median = 16, interquartile range = 9-28). CONCLUSIONS:Unlike in adults, IRD kidneys conferred no survival benefit to pediatric candidates, although they did reduce waiting times. The decision to accept IRD kidneys should balance the advantage of faster transplantation against the risk of infectious transmission.

BACKGROUND:The Organ Procurement and Transplantation Network implemented Share 35 on June 18, 2013, to broaden deceased donor liver sharing within regional boundaries. We investigated whether increased sharing under Share 35 impacted geographic disparity in deceased donor liver transplantation (DDLT) across donation service areas (DSAs). METHODS:Using Scientific Registry of Transplant Recipients June 2009 to June 2017, we identified 86 083 adult liver transplant candidates and retrospectively estimated Model for End-Stage Liver Disease (MELD)-adjusted DDLT rates using nested multilevel Poisson regression with random intercepts for DSA and transplant program. From the variance in DDLT rates across 49 DSAs and 102 programs, we derived the DSA-level median incidence rate ratio (MIRR) of DDLT rates. MIRR is a robust metric of heterogeneity across each hierarchical level; larger MIRR indicates greater disparity. RESULTS:MIRR was 2.18 pre-Share 35 and 2.16 post-Share 35. Thus, 2 candidates with the same MELD in 2 different DSAs were expected to have a 2.2-fold difference in DDLT rate driven by geography alone. After accounting for program-level heterogeneity, MIRR was attenuated to 2.10 pre-Share 35 and 1.96 post-Share 35. For candidates with MELD 15-34, MIRR decreased from 2.51 pre- to 2.27 post-Share 35, and for candidates with MELD 35-40, MIRR increased from 1.46 pre- to 1.51 post-Share 35, independent of program-level heterogeneity in DDLT. DSA-level heterogeneity in DDLT rates was greater than program-level heterogeneity pre- and post-Share 35. CONCLUSIONS:Geographic disparity substantially impacted DDLT rates before and after Share 35, independent of program-level heterogeneity and particularly for candidates with MELD 35-40. Despite broader sharing, geography remains a major determinant of access to DDLT.