The Impact of Increased Allocation Priority for Children Awaiting Liver Transplant: A Liver Simulated Allocation Model (LSAM) Analysis.
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SUBMITTER: Perito ER
PROVIDER: S-EPMC6428603 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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The Impact of Increased Allocation Priority for Children Awaiting Liver Transplant: A Liver Simulated Allocation Model (LSAM) Analysis.
Perito Emily R ER Mogul Douglas B DB VanDerwerken Douglas D Mazariegos George G Bucuvalas John J Book Linda L Horslen Simon S Kim Heung B HB Miloh Tamir T Ng Vicky V Reyes Jorge J Rodriguez-Davalos Manuel I MI Valentino Pamela L PL Gentry Sommer S Hsu Evelyn E
Journal of pediatric gastroenterology and nutrition 20190401 4
<h4>Objective</h4>The aim of the study was to investigate the impact of prioritizing infants, children, adolescents, and the sickest adults (Status 1) for deceased donor livers. We compared outcomes under two "SharePeds" allocation schema, which prioritize children and Status 1 adults for national sharing and enhanced access to pediatric donors or all donors younger than 35 years, to outcomes under the allocation plan approved by the Organ Procurement and Transplant Network in December 2017 (Org ...[more]
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Project description:BACKGROUND & AIM:The goal of organ allocation is to distribute a scarce resource equitably to the sickest patients. In the United States, the Model for End-stage Liver Disease (MELD) is used to allocate livers for transplantation. Patients with greater MELD scores are at greater risk of death on the waitlist and are prioritized for liver transplant (LT). The MELD is capped at 40 however, and patients with calculated MELD scores >40 are not prioritized despite increased mortality. We aimed to evaluate waitlist and post-transplant survival stratified by MELD to determine outcomes in patients with MELD >40. METHODS:Using United Network for Organ Sharing data, we identified patients listed for LT from February 2002 through to December 2012. Waitlist candidates with MELD ?40 were followed for 30days or until the earliest occurrence of death or transplant. RESULTS:Of 65,776 waitlisted patients, 3.3% had MELD ?40 at registration, and an additional 7.3% had MELD scores increase to ?40 after waitlist registration. A total of 30,369 (46.2%) underwent LT, of which 2,615 (8.6%) had MELD ?40 at transplant. Compared to MELD 40, the hazard ratio of death within 30days of registration was 1.4 (95% CI 1.2-1.6) for patients with MELD 41-44, 2.6 (95% CI 2.1-3.1) for MELD 45-49, and 5.0 (95% CI 4.1-6.1) for MELD ?50. There was no difference in 1- and 3-year survival for patients transplanted with MELD >40 compared to MELD=40. A survival benefit associated with LT was seen as MELD increased above 40. CONCLUSIONS:Patients with MELD >40 have significantly greater waitlist mortality but comparable post-transplant outcomes to patients with MELD=40 and, therefore, should be given priority for LT. Uncapping the MELD will allow more equitable organ distribution aligned with the principle of prioritizing patients most in need. Lay summary: In the United States (US), organs for liver transplantation are allocated by an objective scoring system called the Model for End-stage Liver Disease (MELD), which aims to prioritize the sickest patients for transplant. The greater the MELD score, the greater the mortality without liver transplant. The MELD score, however, is artificially capped at 40 and thus actually disadvantages the sickest patients with end-stage liver disease. Analysis of the data advocates uncapping the MELD score to appropriately prioritize the patients most in need of a liver transplant.
| S-EPMC7735955 | biostudies-literature
Project description:Offer acceptance practices may cause geographic variability in allocation Model for End-Stage Liver Disease (aMELD) score at transplant and could magnify the effect of donor supply and demand on aMELD variability. To evaluate these issues, offer acceptance practices of liver transplant programs and donation service areas (DSAs) were estimated using offers of livers from donors recovered between January 1, 2016, and December 31, 2016. Offer acceptance practices were compared with liver yield, local placement of transplanted livers, donor supply and demand, and aMELD at transplant. Offer acceptance was associated with liver yield (odds ratio, 1.32; P < 0.001), local placement of transplanted livers (odds ratio, 1.34; P < 0.001), and aMELD at transplant (average aMELD difference, -1.62; P < 0.001). However, the ratio of donated livers to listed candidates in a DSA (ie, donor-to-candidate ratio) was associated with median aMELD at transplant (r = -0.45; P < 0.001), but not with offer acceptance (r = 0.09; P = 0.50). Additionally, the association between DSA-level donor-to-candidate ratios and aMELD at transplant did not change after adjustment for offer acceptance. The average squared difference in median aMELD at transplant across DSAs was 24.6; removing the effect of donor-to-candidate ratios reduced the average squared differences more than removing the effect of program-level offer acceptance (33% and 15% reduction, respectively). Offer acceptance practices and donor-to-candidate ratios independently contributed to geographic variability in aMELD at transplant. Thus, neither offer acceptance nor donor-to-candidate ratios can explain all of the geographic variability in aMELD at transplant. Liver Transplantation 24 478-487 2018 AASLD.
| S-EPMC5869092 | biostudies-literature
Project description:Background & aimsPortal hypertension contributes to the pathogenesis of malnutrition and sarcopenia in cirrhosis via multiple mechanisms. Terlipressin is a vasopressin analogue that we administer via continuous outpatient infusion, as a bridge to transplantation in patients with hepatorenal syndrome or refractory ascites. We describe, for the first time, the impact of outpatient terlipressin on nutritional and muscle parameters.MethodsNutrition (subjective global assessment), handgrip strength, dietary intake (energy, protein), frequency of paracentesis and severity of liver disease (model for end-stage liver disease score) were prospectively recorded at terlipressin commencement and follow-up (transplantation, cessation or census date).ResultsNineteen patients were included (89% male, median age 59.6 years, median model for end-stage liver disease score 24), of whom 12 had hepatorenal syndrome and 7 had refractory ascites. All patients were malnourished at baseline, 63% (n = 12) had sarcopenic-range grip strength, and mean paracentesis frequency was 2.86 ± 1.62/month. Median duration of terlipressin was 51 days (interquartile range 29-222). Fourteen patients (74%) were transplanted, 2 delisted (10%) and 3 (16%) continued terlipressin. Energy and protein intake improved significantly following terlipressin, from 17.94 ± 5.43 kcal/kg to 27.70 ± 7.48 kcal/kg, and 0.74 ± 0.28 g/kg to 1.16 ± 0.31 g/kg, respectively (both p < 0.001). Handgrip strength increased from 25.36 ± 8.13 kg to 28.49 ± 7.63 kg (p = 0.001). Linear regression analysis demonstrated hand grip strength increased 0.075% for every 1-day of terlipressin (p = 0.005). The frequency of large-volume paracentesis reduced by 46%, to 1.57 ± 1.51/month (p = 0.001).ConclusionContinuous terlipressin infusion reduces the complications of portal hypertension and is associated with an improvement in nutritional and muscle parameters in patients on the liver transplant waiting list, in whom such characteristics usually demonstrate progressive decline. This validates both the aetiological role of portal hypertension in malnutrition and represents a promising new anabolic therapy.Lay summaryMalnutrition and poor muscle strength are common in liver disease and often get worse while patients await liver transplant. Terlipressin is a medication used to treat portal hypertension in patients with hepatorenal syndrome. It is usually given for a few days or weeks in patients confined to hospital. Our centre provides outpatient terlipressin for weeks to months as a bridge to liver transplant. In patients treated with terlipressin at our hospital, we observed a substantial increase in their dietary intake and muscle strength, which may improve their quality of life and outcomes after liver transplant.
| S-EPMC7001556 | biostudies-literature
Project description:BackgroundSensitization to human leukocyte antigen (HLA) from red blood cell (RBC) transfusion is poorly quantified and is based on outdated, insensitive methods. The objective was to evaluate the effect of transfusion on the breadth, magnitude and specificity of HLA antibody formation using sensitive and specific methods.MethodsTransfusion, demographic and clinical data from the US Renal Data System were obtained for patients on dialysis awaiting primary kidney transplant who had ? 2 HLA antibody measurements using the Luminex single-antigen bead assay. One cohort included patients with a transfusion (n = 50) between two antibody measurements matched with up to four nontransfused patients (n = 155) by age, sex, race and vintage (time on dialysis). A second crossover cohort (n = 25) included patients with multiple antibody measurements before and after transfusion. We studied changes in HLA antibody mean fluorescence intensity (MFI) and calculated panel reactive antibody (cPRA).ResultsIn the matched cohort, 10 of 50 (20%) transfused versus 6 of 155 (4%) nontransfused patients had a ? 10 HLA antibodies increase of >3000 MFI (P = 0.0006); 6 of 50 (12%) transfused patients had a ? 30 antibodies increase (P = 0.0007). In the crossover cohort, the number of HLA antibodies increasing >1000 and >3000 MFI was higher in the transfused versus the control period, P = 0.03 and P = 0.008, respectively. Using a ? 3000 MFI threshold, cPRA significantly increased in both matched (P = 0.01) and crossover (P = 0.002) transfused patients.ConclusionsAmong prospective primary kidney transplant recipients, RBC transfusion results in clinically significant increases in HLA antibody strength and breadth, which adversely affect the opportunity for future transplant.
| S-EPMC3811060 | biostudies-literature
Project description:The Model for End Stage Liver Disease (MELD) was originally developed based on data from patients who underwent the transjugular intrahepatic portosystemic shunt procedure. An updated MELD based on data from patients awaiting liver transplantation should improve mortality prediction and allocation efficiency.Wait-list data from adult primary liver transplantation candidates from the Organ Procurement and Transplantation Network were divided into a model derivation set (2005-2006; n=14,214) and validation set (2007-2008; n=13,945). Cox regression analysis was used to derive and validate an optimized model that updated coefficients and upper and lower bounds for MELD components and included serum levels of sodium. Main outcomes measure was ability to predict 90-day mortality of patients on the liver transplantation wait list.Optimized MELD score updated coefficients and implemented new upper and lower bounds for creatinine (0.8 and 3.0 mg/dL, respectively) and international normalized ratio (1 and 3, respectively). Serum sodium concentrations significantly predicted mortality, even after adjusting for the updated MELD model. The final model, based on updated fit of the 4 variables (ie, bilirubin, creatinine, international normalized ratio, and sodium) had a modest yet statistically significant gain in discrimination (concordance: 0.878 vs 0.865; P<.01) in the validation dataset. Utilization of the new score could affect up to 12% of patients (based on changed score for 459 of 3981 transplants in the validation set).Modification of MELD score to update coefficients, change upper and lower bounds, and incorporate serum sodium levels improved wait-list mortality prediction and should increase efficiency of allocation of donated livers.
| S-EPMC4546828 | biostudies-literature
Project description:ImportanceLiving-donor liver transplant (LDLT) offers advantages over deceased-donor liver transplant (DDLT) of improved intention-to-treat outcomes and management of the shortage of deceased-donor allografts. However, conflicting data still exist on the outcomes of LDLT in patients with hepatocellular carcinoma (HCC).ObjectiveTo investigate the potential survival benefit of an LDLT in patients with HCC from the time of waiting list inscription.Design, setting, and participantsThis multicenter cohort study with an intention-to-treat design analyzed the data of patients aged 18 years or older who had an HCC diagnosis and were on a waiting list for a first transplant. Patients from 12 collaborative centers in Europe, Asia, and the US who were on a transplant waiting list between January 1, 2000, and December 31, 2017, composed the international cohort. The Toronto cohort comprised patients from 1 transplant center in Toronto, Ontario, Canada who were on a waiting list between January 1, 2000, and December 31, 2015. The international cohort centers performed either an LDLT or a DDLT, whereas the Toronto cohort center was selected for its capability to perform both LDLT and DDLT. The benefit of LDLT was tested in the 2 cohorts before and after undergoing an inverse probability of treatment weighting (IPTW) analysis. Data were analyzed from February 1 to May 31, 2020.Main outcomes and measuresIntention-to-treat death was defined as a patient death that occurred for any reason and was calculated from the time of waiting list inscription for liver transplant to the last follow-up date (December 31, 2019). Four multivariable Cox proportional hazards regression models for intention-to-treat death were created.ResultsA total of 3052 patients were analyzed in the international cohort, of whom 2447 were men (80.2%) and the median (IQR) age at first referral was 58 (53-63) years. The Toronto cohort comprised 906 patients, of whom 743 were men (82.0%) and the median (IQR) age at first referral was 59 (53-63) years. In all the settings, LDLT was an independent protective factor, reducing the risk of overall death by 49% in the pre-IPTW analysis for the international cohort (HR, 0.51; 95% CI, 0.36-0.71; P < .001), 33% in the post-IPTW analysis for the international cohort (HR, 0.67; 95% CI, 0.53-0.85; P = .001), 43% in the pre-IPTW analysis for the Toronto cohort (HR, 0.57; 95% CI, 0.45-0.73; P < .001), and 48% in the post-IPTW analysis for the Toronto cohort (HR, 0.52; 95% CI, 0.42 to 0.65; P < .001). The discriminatory ability of the mathematical models further improved in all of the cases in which LDLT was incorporated.Conclusions and relevanceThis study suggests that having a potential live donor could decrease the intention-to-treat risk of death in patients with HCC who are on a waiting list for a liver transplant. This benefit is associated with the elimination of the dropout risk and has been reported in centers in which both LDLT and DDLT options are equally available.
| S-EPMC8281041 | biostudies-literature
Project description:BackgroundAllocation of scarce resources during a pandemic extends to the allocation of vaccines when they eventually become available. We describe a framework for priority vaccine allocation that employed a cross-disciplinary approach, guided by ethical considerations and informed by local risk assessment.MethodsPublished and grey literature was reviewed, and augmented by consultation with key informants, to collate past experience, existing guidelines and emerging strategies for pandemic vaccine deployment. Identified ethical issues and decision-making processes were also included. Concurrently, simulation modelling studies estimated the likely impacts of alternative vaccine allocation approaches. Assembled evidence was presented to a workshop of national experts in pandemic preparedness, vaccine strategy, implementation and ethics. All of this evidence was then used to generate a proposed ethical framework for vaccine priorities best suited to the Australian context.FindingsPublished and emerging guidance for priority pandemic vaccine distribution differed widely with respect to strategic objectives, specification of target groups, and explicit discussion of ethical considerations and decision-making processes. Flexibility in response was universally emphasised, informed by real-time assessment of the pandemic impact level, and identification of disproportionately affected groups. Model outputs aided identification of vaccine approaches most likely to achieve overarching goals in pandemics of varying transmissibility and severity. Pandemic response aims deemed most relevant for an Australian framework were: creating and maintaining trust, promoting equity, and reducing harmful outcomes.InterpretationDefining clear and ethically-defendable objectives for pandemic response in context aids development of flexible and adaptive decision support frameworks and facilitates clear communication and engagement activities.
| S-EPMC7779078 | biostudies-literature
Project description:BackgroundHuman albumin/dextran (HA-D), bovine-gelatin (BG), and packed red blood cells plus plasma have been used in European and North-American clinical trials of normothermic ex situ liver perfusion (NEsLP). We compared the effects of these perfusates in a porcine model during NEsLP and after transplantation.MethodsPorcine livers were retrieved 30 minutes after circulatory death. After 5 hours of NEsLP, grafts were transplanted. Three groups (n = 6) were assessed (HA-D vs BG vs whole blood [WB]). One group of static cold storage (SCS) was evaluated for comparison with the perfusion groups. Hemodynamic variables, liver and endothelial injury, and function were assessed during NEsLP and posttransplantation.ResultsHepatic artery flow was higher since the beginning of NEsLP in the HA-D group (HA-D, 238 ± 90 mL/min vs BG, 97 ± 33 mL/min vs WB, 148 ± 49 mL/min; P = 0.01). Hyaluronic acid was lower in the HA-D at the end of perfusion (HA-D, 16.28 ± 7.59 ng/μL vs BG, 76.05 ± 15.30 ng/μL vs WB, 114 ± 46 ng/μL; P < 0.001). After transplant, aspartate aminotransferase was decreased in the HA-D group when compared with the rest of the groups (HA-D, 444 ± 226 IU/L vs BG, 1033 ± 694 IU/L vs WB, 616 ± 444 IU/L vs SCS, 2235 ± 1878 IU/L). At 5 hours after transplant, lactate was lower in the HA-D group (HA-D, 3.88 ± 1.49 mmol/L vs BG, 7.79 ± 2.68 mmol/L vs WB, 8.16 ± 3.86 mmol/L vs SCS, 9.06 ± 3.54 mmol/L; P = 0.04). International Normalized Ratio was improved in HA-D group compared to the rest of the groups (HA-D, 1.23 ± 0.30 vs BG, 1.63 ± 0.20 vs WB, 1.50 ± 0.31 vs SCS, 1.97 ± 1.55; P = 0.03) after transplantation. In contrast, BG displayed lower aspartate aminotransferase levels during NEsLP (HA-D, 183 ± 53 IU/L vs BG, 142 ± 52 IU/L vs WB, 285 ± 74 IU/L; P = 0.01) and less cleaved-caspase-3 staining (HA-D, 2.05 ± 0.73% vs BG, 0.95 ± 1.14% vs WB, 1.74 ± 0.54% vs SCS, 7.95 ± 2.38%) compared with the other groups. On the other hand, the bile from the WB showed higher pH (HA-D, 7.54 ± 0.11 vs BG, 7.34 ± 0.37 vs WB, 7.59 ± 0.18) and lower glucose levels (HA-D, 0.38 ± 0.75 mmol/L vs BG, 1.42 ± 1.75 mmol/L vs WB, 0 ± 0 mmol/L) by the end of perfusion.ConclusionsOverall HA-D displayed more physiologic conditions during NEsLP that were reflected in less graft injury and improved liver function and survival after transplantation. Optimization of the perfusates based on the beneficial effects found with these different solutions would potentially improve further the outcomes through the use of NEsLP in marginal grafts.
| S-EPMC6445654 | biostudies-literature
Project description:Early studies of national data suggest that the Share 35 allocation policy increased liver transplants without compromising posttransplant outcomes. Changes in center-specific volumes and practice patterns in response to the national policy change are not well characterized. Understanding center-level responses to Share 35 is crucial for optimizing the policy and constructing effective future policy revisions. Data from the United Network for Organ Sharing were analyzed to compare center-level volumes of allocation-Model for End-Stage Liver Disease (aMELD) ? 35 transplants before and after policy implementation. There was significant center-level variation in the number and proportion of aMELD ? 35 transplants performed from the pre- to post-Share 35 period; 8 centers accounted for 33.7% of the total national increase in aMELD ? 35 transplants performed in the 2.5-year post-Share 35 period, whereas 25 centers accounted for 65.0% of the national increase. This trend correlated with increased listing at these centers of patients with Model for End-Stage Liver Disease (MELD) ? 35 at the time of initial listing. These centers did not overrepresent the total national volume of liver transplants. Comparison of post-Share 35 aMELD to calculated time-of-transplant (TOT) laboratory MELD scores showed that only 69.6% of patients transplanted with aMELD ? 35 maintained a calculated laboratory MELD ? 35 at the TOT. In conclusion, Share 35 increased transplantation of aMELD ? 35 recipients on a national level, but the policy asymmetrically impacted practice patterns and volumes of a subset of centers. Longer-term data are necessary to assess outcomes at centers with markedly increased volumes of high-MELD transplants after Share 35. Liver Transplantation 23 741-750 2017 AASLD.
| S-EPMC5494984 | biostudies-literature
Project description:Simulated Gastrointestinal Model Targeted loci environmental
| PRJNA658988 | ENA