Chronic Kidney Disease in Liver Transplant Candidates: A Rising Burden Impacting Post-Liver Transplant Outcomes.
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ABSTRACT:
SUBMITTER: Cullaro G
PROVIDER: S-EPMC8056970 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Since the Model for End-stage Liver Disease (MELD) allocation system was implemented, the proportion of simultaneous liver-kidney transplantation (SLKT) has increased significantly. However, whether racial/ethnic disparities exist in access to SLKT and post-SLKT survival remains understudied. METHODS:A retrospective cohort of patients aged ?18 years with renal dysfunction on the liver transplant (LT) waiting list was obtained from Organ Procurement and Transplantation Network. Renal dysfunction was defined as estimated glomerular filtration rate <60?mL/min/1.73 m at listing for LT. Multilevel time-to-competing-events regression adjusting for center effect was used to examine the likelihood of receiving SLKT. Inverse probability of treatment weighted survival analyses were used to analyze posttransplant mortality outcomes. RESULTS:For patients with renal dysfunction at listing for LT, not listed for simultaneous kidney transplant, non-Hispanic black (NHB) and Hispanic patients were more likely to receive SLKT than non-Hispanic white (NHW) patients (NHB: multivariable-adjusted hazard ratio [aHR] 2.57; 95% confidence interval [CI], 1.42-4.65; Hispanic: aHR, 2.03; 95% CI, 1.14-3.60). For post-SLKT outcomes, compared to NHW patients, NHB patients had a lower mortality risk before 24 months (aHR, 0.80; 95% CI, 0.65-0.97) but had a higher mortality risk (aHR, 2.00; 95% CI, 1.59-2.55) afterward; in contrast, Hispanic patients had a lower overall mortality risk than NHW patients (aHR, 0.61; 95% CI, 0.51-0.74). CONCLUSIONS:In the MELD era, racial/ethnic differences exist in access and survival of SLKT for patients with renal dysfunction at listing for LT. Future studies are warranted to examine whether these differences remain in the post-SLK allocation policy era.
| S-EPMC6779036 | biostudies-literature
Project description:IntroductionPreemptive wait-listing of deceased donor kidney transplant (DDKT) candidates before maintenance dialysis increases the likelihood of transplantation and improves outcomes among transplant patients. Previous studies have identified substantial disparities in rates of preemptive listing, but a gap exists in examining geographic sources of disparities, particularly for sub-regional units. Identifying small area hot spots where delayed listing is particularly prevalent may more effectively inform both health policy and regionally appropriate interventions.MethodsWe conducted a retrospective cohort study utilizing 2010-2020 Scientific Registry of Transplant Recipients (SRTR) data for all DDKT candidates to examine overall and race-stratified geospatial hot spots of post-dialysis wait-listing in U.S. zip code tabulation areas (ZCTA). Three geographic clustering methods were utilized to identify robust statistically significant hot spots of post-dialysis wait-listing.ResultsNovel sub-regional hot spots were identified in the southeast, southwest, Appalachia, and California, with a majority existing in the southeast. Race-stratified results were more nuanced, but broadly reflected similar patterns. Comparing transplant candidates in hot spots to candidates in non-clusters indicated a strong association between residence in hot spots and high area deprivation (OR: 6.76, 95%CI: 6.52-7.02), indicating that improving access healthcare in these areas may be particularly beneficial.ConclusionOur study identified overall and race-stratified hot spots with low rates of preemptive wait list placement in the U.S., which may be useful for prospective healthcare policy and interventions via targeting of these narrowly defined geographical areas.
| S-EPMC10078213 | biostudies-literature
Project description:Hepatitis E virus (HEV) has been reported to cause acute and chronic hepatitis in those with HIV infection and among solid organ transplant recipients in Europe. Limited data indicate that HEV is endemic in the United States, but the prevalence and significance of HEV infection among those with HIV and awaiting solid organ transplantation is unknown. We evaluated anti-HEV IgM and IgG antibodies and HEV RNA in 166 HIV-infected solid organ transplant candidates enrolled in the NIH HIV-Transplant Cohort. Overall prevalence of anti-HEV IgG approached 20% in both liver and renal transplant candidates. Evidence of recent infection was present in approximately 2% of liver transplant candidates and none of the kidney transplant candidates. HEV RNA was not detected in any patient. We conclude that markers of HEV infection are frequent among candidates for transplantation, but active, ongoing viremia is not seen. Evidence of recent infection (acute on chronic) liver disease was present in liver but not kidney recipients.
| S-EPMC4082745 | biostudies-literature
Project description:Nonstandard exceptions requests (NSERs), in which transplant centers appeal on a case-by-case basis for Pediatric End-Stage Liver Disease/Mayo End-Stage Liver Disease points, have been highly utilized for pediatric liver transplant candidates. We evaluated whether NSE outcomes are associated with waitlist and posttransplant mortality. United Network for Organ Sharing (UNOS) Scientific Registry of Transplant Recipients data on pediatric liver transplant candidates listed in 2009-2014 were analyzed after excluding those granted automatic UNOS exceptions. Of 2581 pediatric waitlist candidates, 44% had an NSE request. Of the 1134 children with NSERs, 93% were approved and 7% were denied. For children 2-18 years at listing, NSER denial increased the risk of waitlist mortality or removal for being too sick (subhazard ratio 2.99, 95% confidence interval [CI] 1.26-7.07, p = 0.01 in multivariate analysis). For children younger than 2 years, NSER denial did not impact waitlist mortality/removal. Children with NSER approved had reduced risk of graft loss 3 years posttransplant in univariate but not multivariable analysis (odds ratio 0.73, 95% CI 0.53-1.01, p = 06). Those with NSER denial had a higher risk of posttransplant death than those with no NSER (hazard ratio 2.43, 95% CI 0.99-5.95, p = 0.05, multivariable analysis), but NSER approval did not impact posttransplant death. Further research on NSER utilization in pediatric liver transplant is needed to optimize organ allocation and outcomes for children.
| S-EPMC5083236 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide. It is expected that non-alcoholic steatohepatitis (NASH), NASH-related cirrhosis and its decompensated forms will increase further in the next two decades. Acute-on-chronic liver failure (ACLF) is a distinct syndrome characterized by rapid deterioration of liver function in patients with chronic liver disease that is associated with development of one or more organ failures, and carries a very high short-term mortality. There is a paucity of data on ACLF in patients with NASH cirrhosis. Recent studies have shown that although ACLF incidence due to NASH is lower when compared to other etiologies, NASH is the fastest growing liver disease etiology among all ACLF hospitalizations. Higher rates of infections, as a precipitating factor, and circulatory failure were noted in this population. Metabolic derangements such as obesity and diabetes might also play a confounding role in the pathophysiology, clinical course, and prognosis of NASH patients with ACLF. Patients with ACLF due to NASH have shown a lower inpatient mortality despite a longer hospital length-of-stay and a higher 28- and 90-day mortality. Patients with ACLF should be promptly transferred to a transplant center and evaluated for liver transplantation (LT). Optimal prognostic scores, timing of LT, and the best bridge to LT therapy and treatment of post-LT complications need to be elucidated in prospective studies.
| S-EPMC7063516 | biostudies-literature
Project description:BackgroundDespite the increasing prevalence of end-stage liver disease in older adults, there is no consensus to determine suitability for liver transplantation (LT) in the elderly. Disparities in LT access exist, with a disproportionately lower percentage of African Americans (AAs) receiving LT. Understanding waitlist outcomes in older adults, specifically AAs, will identify opportunities to improve LT access for this vulnerable population.MethodsAll adult, liver-only white and AA LT waitlist candidates (January 1, 2003 to October 1, 2015) were identified in the Scientific Registry of Transplant Recipients. Age and race categories were defined: younger white (age <60 years), younger AA, older white (age, ≥60 years), and older AA. Outcomes were delisting, transplantation, and mortality and were modeled using Fine and Gray competing risks.ResultsAmong 101 805 candidates, 58.4% underwent transplantation, 14.7% died while listed, and 21.4% were delisted. Among those delisted, 36.1% died, whereas 7.4% were subsequently relisted. Both older AAs and older whites were more likely than younger whites to be delisted and to die after delisting. Older whites had higher incidence of waitlist mortality than younger whites (subdistribution hazard ratio, 1.07; 95% confidence interval, 1.01-1.13). All AAs and older whites had decreased incidence of LT, compared with younger whites.ConclusionsBoth older age and AA race were associated with decreased cumulative incidence of transplantation. Independent of race, older candidates had increased incidences of delisting and mortality after delisting than younger whites. Our findings support the need for interventions to ensure medical suitability for LT among older adults and to address disparities in LT access for AAs.
| S-EPMC6509018 | biostudies-literature
Project description:BackgroundIn December 2018, United Network for Organ Sharing approved an allocation scheme based on recipients' geographic distance from a deceased donor (acuity circles [ACs]). Previous analyses suggested that ACs would reduce waitlist mortality overall, but their impact on pediatric subgroups was not considered.MethodsWe applied Scientific Registry of Transplant Recipients data from 2011 to 2016 toward the Liver Simulated Allocation Model to compare outcomes by age and illness severity for the United Network for Organ Sharing-approved AC and the existing donor service area-/region-based allocation schemes. Means from each allocation scheme were compared using matched-pairs t tests.ResultsDuring a 3-year period, AC allocation is projected to decrease waitlist deaths in infants (39 versus 55; P < 0.001), children (32 versus 50; P < 0.001), and teenagers (15 versus 25; P < 0.001). AC allocation would increase the number of transplants in infants (707 versus 560; P < 0.001), children (677 versus 547; P < 0.001), and teenagers (404 versus 248; P < 0.001). AC allocation led to decreased median pediatric end-stage liver disease/model for end-stage liver disease at transplant for infants (29 versus 30; P = 0.01), children (26 versus 29; P < 0.001), and teenagers (26 versus 31; P < 0.001). Additionally, AC allocation would lead to fewer transplants in status 1B in children (97 versus 103; P = 0.006) but not infants or teenagers. With AC allocation, 77% of pediatric donor organs would be allocated to pediatric candidates, compared to only 46% in donor service area-/region-based allocation (P < 0.001).ConclusionsAC allocation will likely address disparities for pediatric liver transplant candidates and recipients by increasing transplants and decreasing waitlist mortality. It is more consistent with federally mandated requirements for organ allocation.
| S-EPMC7319877 | biostudies-literature
Project description:In nontransplant patients with chronic hepatitis C virus (HCV), HCV genotype has been linked with a differential response to antiviral therapy, risk of steatosis and fibrosis, as well as all-cause mortality, but the role of HCV genotypes in posttransplant disease progression is less clear.Using the multicenter CRUSH-C cohort, genotype-specific rates of advanced fibrosis, HCV-specific graft loss and response of antiviral therapy were examined.Among 745 recipients (605 [81%] genotype 1, 53 [7%] genotype 2, and 87 [12%] genotype 3), followed for a median of 3.1 years (range, 2.0-8.0), the unadjusted cumulative rate of advanced fibrosis at 3 years was 31%, 19%, and 19% for genotypes 1, 2, and 3 (P = 0.008). After multivariable adjustment, genotype remained a significant predictor, with genotype 2 having a 66% lower risk (P = 0.02) and genotype 3 having a 41% lower risk (P = 0.07) of advanced fibrosis compared to genotype 1 patients. The cumulative 5-year rates of HCV-specific graft survival were 84%, 90%, and 94% for genotypes 1, 2, and 3 (P = 0.10). A total of 37% received antiviral therapy, with higher rates of sustained virologic response in patients with genotype 2 (hazard ratios, 5.10; P = 0.003) and genotype 3 (hazard ratios, 3.27; P = 0.006) compared to patients with genotype 1.Risk of advanced fibrosis and response to therapy are strongly influenced by genotype. Liver transplantation recipients with HCV genotype 1 have the highest risk of advanced fibrosis and lowest sustained virologic response rate. These findings highlight the need for genotype-specific management strategies.
| S-EPMC4672637 | biostudies-literature
Project description:ImportanceIn the United States, substantial disparities in access to kidney transplant exist for wait-listed candidates with end-stage renal disease. The implications of transplant centers' willingness to accept kidney offers for access to transplant and mortality outcomes are unknown.ObjectiveTo determine the outcomes for wait-listed kidney transplant candidates after the transplant center's refusal of a deceased donor kidney offer.Design, setting, and participantsThis cohort study obtained data from the United Network for Organ Sharing Potential Transplant Recipient data set on all deceased donor kidney offers in the United States made between January 1, 2008, and December 31, 2015. The final study cohort included adult patients who were wait-listed for kidney transplant and received at least 1 allograft offer during the study period (N?=?280?041). Data analysis was conducted from June 1, 2018, to March 30, 2019.ExposureCandidate state of residence.Main outcomes and measuresWaiting list outcome event groups included received deceased donor allograft, received living donor allograft, died while on the waiting list, removed from the waiting list without a transplant, or still on the waiting list at the end of follow-up.ResultsAmong the 280?041 kidney transplant candidates included in the study, the mean (SD) age at wait-listing was 51.1 (13.1) years, and male patients were predominant (171 517 [61.2%]). In this cohort, 81 750 candidates (29.2%) received a deceased donor kidney allograft, 30 870 (11.0%) received a living donor allograft, 25 967 (9.3%) died while on the waiting list, and 59 359 (21.2%) were removed from the waiting list. Overall, 10 candidates with at least 1 previous allograft offer died each day during the study period. Time to first offer was similar for candidates who received deceased donor kidney allograft compared with those who died while waiting (median [interquartile range {IQR}] time, 79 [16-426] days vs 78 [17-401] days, respectively). Deceased donor allograft recipients had a median of 17 offers (IQR, 6-44) over 422 days (IQR, 106-909 days), whereas candidates who died while waiting received a median of 16 offers (IQR, 6-41) over 651 days (IQR, 304-1117 days). Most kidneys (84%) were declined on behalf of at least 1 candidate before being accepted for transplant. As reported by centers, organ or donor quality concerns accounted for 8 416 474 (92.6%) of all declined offers, whereas offers were infrequently refused because of patient-related factors (232 193 [2.6%]), logistical limitations (49 492 [0.5%]), or other concerns. The odds of death after an offer and the median number of offers received prior to death varied considerably by state.Conclusions and relevanceThis study found that transplant candidates appeared to receive a large number of viable deceased donor kidney offers that were refused on their behalf by transplant centers, potentially exacerbating the detrimental consequences of the organ shortage; increased transparency in organ allocation process and decisions may improve patient-centered care and access to kidney transplant.
| S-EPMC6724162 | biostudies-literature
Project description:Under Share 35, deceased donor (DD) livers are offered regionally to candidates with Model for End-Stage Liver Disease (MELD) scores ≥35 before being offered locally to candidates with MELD scores <35. Using Scientific Registry of Transplant Recipients data from June 2013 to June 2015, we identified 1768 DD livers exported to regional candidates with MELD scores ≥35 who were transplanted at a median MELD score of 39 (interquartile range [IQR] 37-40) with 30-day posttransplant survival of 96%. In total, 1764 (99.8%) exports had an ABO-compatible candidate in the recovering organ procurement organization (OPO), representing 1219 unique reprioritized candidates who would have had priority over the regional candidate under pre-Share 35 allocation. Reprioritized candidates had a median waitlist MELD score of 31 (IQR 27-34) when the liver was exported. Overall, 291 (24%) reprioritized candidates had a comparable MELD score (within 3 points of the regional recipient), and 209 (72%) were eventually transplanted in 11 days (IQR 3-38 days) using a local (50%), regional (50%) or national (<1%) liver; 60 (21%) died, 13 (4.5%) remained on the waitlist and nine (3.1%) were removed for other reasons. Of those eventually transplanted, MELD score did not increase in 57%; it increased by 1-3 points in 37% and by ≥4 points in 5.7% after the export. In three cases, OPOs exchanged regional exports within a 24-h window. The majority of comparable reprioritized candidates were not disadvantaged; however, 21% died after an export.
| S-EPMC5433796 | biostudies-literature