Search

Introduction: In 2013, a new liver transplant allocation policy (Share 35) aimed to reduce waitlist-mortality was introduced in the United States. Regional organ sharing for recipients with a MELD score of ≥35 was prioritized over local allocation to those with lower MELD scores. Our aim was to assess the changes in perioperative mortality following the introduction of Share 35 as well as changes in patients’ short-term 7-day survival, patients discharged alive and 1-year survival. Analyses were also carried out for the subgroups of patients with MELD scores ≥ and < 35. Methods: We used data from the Scientific Registry of Transplant Recipients and included liver transplants between March 2002 and December 2018 in this retrospective cohort study. Perioperative mortality was defined as death during and within two days of liver transplant. We used robust interrupted time series analyses to evaluate the impact of Share 35 on mortality. Results: We included 90 002 liver transplants in our analysis and observed a decreasing trend in perioperative mortality over time (−.061 deaths per 1000 cases per month, 95% CI −.084 to −.037, p <.001). Share 35 was not associated with a change in perioperative mortality (p =.33), short-term 7-day survival (p =.48), survival to discharge (p =.56), or 1-year survival (p =.27). Conclusions: Prioritizing sicker recipients with a MELD score ≥35 for liver transplantation was not associated with a change in postoperative mortality.

Introduction: In 2013, a new liver transplant allocation policy (Share 35) aimed to reduce waitlist-mortality was introduced in the United States. Regional organ sharing for recipients with a MELD score of ≥35 was prioritized over local allocation to those with lower MELD scores. Our aim was to assess the changes in perioperative mortality following the introduction of Share 35 as well as changes in patients’ short-term 7-day survival, patients discharged alive and 1-year survival. Analyses were also carried out for the subgroups of patients with MELD scores ≥ and < 35. Methods: We used data from the Scientific Registry of Transplant Recipients and included liver transplants between March 2002 and December 2018 in this retrospective cohort study. Perioperative mortality was defined as death during and within two days of liver transplant. We used robust interrupted time series analyses to evaluate the impact of Share 35 on mortality. Results: We included 90 002 liver transplants in our analysis and observed a decreasing trend in perioperative mortality over time (−.061 deaths per 1000 cases per month, 95% CI −.084 to −.037, p <.001). Share 35 was not associated with a change in perioperative mortality (p =.33), short-term 7-day survival (p =.48), survival to discharge (p =.56), or 1-year survival (p =.27). Conclusions: Prioritizing sicker recipients with a MELD score ≥35 for liver transplantation was not associated with a change in postoperative mortality.

Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018–2020) and post-AC (2020–2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96–74.05; p = .054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15–0.75; p = .008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p = .04) and pediatric recipients (65% to 15%; p = .002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.

In March 2009, the Scandiatransplant acceptable mismatch program (STAMP) was introduced as a strategy toward improving kidney allocation to highly sensitized patients. Patients with a transplantability score ≤ 2% are potential candidates for the program. Samples are analyzed and acceptable antigens (HLA-A, B, C, DRB1, DRB3/4/5, DQB1, DQA1, DPB1, DPA1) are defined by the local tissue typing laboratory and finally evaluated by a steering committee. In the matching algorithm, patients have the highest priority when the donor's antigens are all among the recipient's own or acceptable HLA antigens. In the period from 2009 to 2020, we have transplanted 278 highly sensitized kidney patients through the program. The graft survival of the STAMP patients was compared with 9002 deceased donor kidney-transplanted patients, transplanted in the same time period. The 10-year graft survival was 73.4% (95% CI: 60.3-90.0) for STAMP and 82.9% (95% CI: 81.6-84.3) for the reference group. (p = .2). In conclusion, the 10-year allograft survival demonstrates that the STAMP allocation algorithm is immunological safe. The program is continuously monitored and evaluated, and the introduction of matching for all HLA loci is a huge improvement to the program and demonstrate technical adaptability as well as clinical flexibility in a de-centralized organization.

In March 2009, the Scandiatransplant acceptable mismatch program (STAMP) was introduced as a strategy toward improving kidney allocation to highly sensitized patients. Patients with a transplantability score ≤ 2% are potential candidates for the program. Samples are analyzed and acceptable antigens (HLA-A, B, C, DRB1, DRB3/4/5, DQB1, DQA1, DPB1, DPA1) are defined by the local tissue typing laboratory and finally evaluated by a steering committee. In the matching algorithm, patients have the highest priority when the donor's antigens are all among the recipient's own or acceptable HLA antigens. In the period from 2009 to 2020, we have transplanted 278 highly sensitized kidney patients through the program. The graft survival of the STAMP patients was compared with 9002 deceased donor kidney-transplanted patients, transplanted in the same time period. The 10-year graft survival was 73.4% (95% CI: 60.3-90.0) for STAMP and 82.9% (95% CI: 81.6-84.3) for the reference group. (p = .2). In conclusion, the 10-year allograft survival demonstrates that the STAMP allocation algorithm is immunological safe. The program is continuously monitored and evaluated, and the introduction of matching for all HLA loci is a huge improvement to the program and demonstrate technical adaptability as well as clinical flexibility in a de-centralized organization.

In March 2009, the Scandiatransplant acceptable mismatch program (STAMP) was introduced as a strategy toward improving kidney allocation to highly sensitized patients. Patients with a transplantability score ≤ 2% are potential candidates for the program. Samples are analyzed and acceptable antigens (HLA-A, B, C, DRB1, DRB3/4/5, DQB1, DQA1, DPB1, DPA1) are defined by the local tissue typing laboratory and finally evaluated by a steering committee. In the matching algorithm, patients have the highest priority when the donor's antigens are all among the recipient's own or acceptable HLA antigens. In the period from 2009 to 2020, we have transplanted 278 highly sensitized kidney patients through the program. The graft survival of the STAMP patients was compared with 9002 deceased donor kidney-transplanted patients, transplanted in the same time period. The 10-year graft survival was 73.4% (95% CI: 60.3-90.0) for STAMP and 82.9% (95% CI: 81.6-84.3) for the reference group. (p = .2). In conclusion, the 10-year allograft survival demonstrates that the STAMP allocation algorithm is immunological safe. The program is continuously monitored and evaluated, and the introduction of matching for all HLA loci is a huge improvement to the program and demonstrate technical adaptability as well as clinical flexibility in a de-centralized organization.

Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018–2020) and post-AC (2020–2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96–74.05; p = .054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15–0.75; p = .008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p = .04) and pediatric recipients (65% to 15%; p = .002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.

In March 2009, the Scandiatransplant acceptable mismatch program (STAMP) was introduced as a strategy toward improving kidney allocation to highly sensitized patients. Patients with a transplantability score ≤ 2% are potential candidates for the program. Samples are analyzed and acceptable antigens (HLA-A, B, C, DRB1, DRB3/4/5, DQB1, DQA1, DPB1, DPA1) are defined by the local tissue typing laboratory and finally evaluated by a steering committee. In the matching algorithm, patients have the highest priority when the donor's antigens are all among the recipient's own or acceptable HLA antigens. In the period from 2009 to 2020, we have transplanted 278 highly sensitized kidney patients through the program. The graft survival of the STAMP patients was compared with 9002 deceased donor kidney-transplanted patients, transplanted in the same time period. The 10-year graft survival was 73.4% (95% CI: 60.3-90.0) for STAMP and 82.9% (95% CI: 81.6-84.3) for the reference group. (p = .2). In conclusion, the 10-year allograft survival demonstrates that the STAMP allocation algorithm is immunological safe. The program is continuously monitored and evaluated, and the introduction of matching for all HLA loci is a huge improvement to the program and demonstrate technical adaptability as well as clinical flexibility in a de-centralized organization.

BackgroundMost patients are listed for liver transplant (LT) following extensive workup as outpatients ("conventional evaluation"). Some patients undergo urgent evaluation as inpatients after being transferred to a transplant center ("expedited evaluation"). We hypothesized that expedited patients would have inferior survival due to disease severity at the time of transplant and shorter workup time.MethodsPatients who underwent evaluation for LT at our institution between 2012 and 2016 were retrospectively reviewed. The expedited and conventional cohorts were defined as above. Living donor LT recipients, combined liver-kidney recipients, acute liver failure patients, and re-transplant patients were excluded. We compared patient characteristics and overall survival between patients who received a transplant following expedited evaluation and those who did not, and between LT recipients based on expedited or conventional evaluation.ResultsFive-hundred and nine patients were included (110 expedited, 399 conventional). There was no difference in graft or patient survival at 1 year for expedited versus conventional LT recipients. In multivariable analysis of overall survival, only Donor Risk Index (HR 1.97, CI 1.04-3.73, P = .037, per unit increase) was associated with increased risk of death.ConclusionsPatients who underwent expedited evaluation for LT had significant demographic and clinical differences from patients who underwent conventional evaluation, but comparable post-transplant survival.

[Abstract] Introduction and objectives: The Index for Mortality Prediction After Cardiac Transplantation (IMPACT) score was derived and validated as a predictor of mortality after heart transplantation (HT). The primary objective of this work is to externally validate the IMPACT score in a contemporary Spanish cohort. Methods: Spanish Heart Transplant Registry data were used to identify adult (>16 years) HT patients between January 2000 and December 2015. Retransplantation, multiorgan transplantation and patients in whom at least one of the variables required to calculate the IMPACT score was missing were excluded from the analysis (N = 2810). Results: Median value of the IMPACT score was five points (IQR: 3, 8). Overall, 1-year survival rate was 79.1%. Kaplan-Meier 1-year survival rates by IMPACT score categories (0-2, 3-5, 6-9, 10-14, ≥15) were 84.4%, 81.5%, 79.3%, 77.3%, and 58.5%, respectively (Log-Rank test: p < .001). Performance analysis showed a good calibration (Hosmer-Lemeshow chi-square for 1 year was 7.56; p = .47) and poor discrimination ability (AUC-ROC .59) of the IMPACT score as a predictive model. Conclusions: In a contemporary Spanish cohort, the IMPACT score failed to accurately predict the risk of death after HT.

In March 2009, the Scandiatransplant acceptable mismatch program (STAMP) was introduced as a strategy toward improving kidney allocation to highly sensitized patients. Patients with a transplantability score ≤ 2% are potential candidates for the program. Samples are analyzed and acceptable antigens (HLA-A, B, C, DRB1, DRB3/4/5, DQB1, DQA1, DPB1, DPA1) are defined by the local tissue typing laboratory and finally evaluated by a steering committee. In the matching algorithm, patients have the highest priority when the donor's antigens are all among the recipient's own or acceptable HLA antigens. In the period from 2009 to 2020, we have transplanted 278 highly sensitized kidney patients through the program. The graft survival of the STAMP patients was compared with 9002 deceased donor kidney-transplanted patients, transplanted in the same time period. The 10-year graft survival was 73.4% (95% CI: 60.3-90.0) for STAMP and 82.9% (95% CI: 81.6-84.3) for the reference group. (p = .2). In conclusion, the 10-year allograft survival demonstrates that the STAMP allocation algorithm is immunological safe. The program is continuously monitored and evaluated, and the introduction of matching for all HLA loci is a huge improvement to the program and demonstrate technical adaptability as well as clinical flexibility in a de-centralized organization.

HLA antibodies are typically produced after exposure to transplanted tissue, pregnancy, and blood products. Sensitization delays access to transplantation and preclude utilization of donor organs. Infections and vaccinations have also been reported to result in HLA antibody formation. It is not known if patients develop HLA antibodies after infection with SARS-CoV-2. Here we analyzed a series of eighteen patients waiting for kidney transplantation who had symptomatic COVID-19 disease and recovered. None of the patients in this initial series developed de novo HLA antibodies. Notably, there was no increase in preexisting HLA antibodies in four highly sensitized patients with a CPRA > 80%. These preliminary data suggest that there may not be a need to repeat HLA antibody testing or perform a physical crossmatch on admission serum before kidney transplant for COVID-19 recovered patients. Data from a large number of patients with different demographics needed.

HLA antibodies are typically produced after exposure to transplanted tissue, pregnancy, and blood products. Sensitization delays access to transplantation and preclude utilization of donor organs. Infections and vaccinations have also been reported to result in HLA antibody formation. It is not known if patients develop HLA antibodies after infection with SARS-CoV-2. Here we analyzed a series of eighteen patients waiting for kidney transplantation who had symptomatic COVID-19 disease and recovered. None of the patients in this initial series developed de novo HLA antibodies. Notably, there was no increase in preexisting HLA antibodies in four highly sensitized patients with a CPRA > 80%. These preliminary data suggest that there may not be a need to repeat HLA antibody testing or perform a physical crossmatch on admission serum before kidney transplant for COVID-19 recovered patients. Data from a large number of patients with different demographics needed.

Living donor liver transplantation (LDLT) enjoys widespread use in Asia, but remains limited to a handful of centers in North America and comprises only 5% of liver transplants performed in the United States. In contrast, living donor kidney transplantation is used frequently in the United States, and has evolved to commonly include paired exchanges, particularly for ABO-incompatible pairs. Liver paired exchange (LPE) has been utilized in Asia, and was recently reported in Canada; here we report the first LPE performed in the United States, and the first LPE to be performed on consecutive days. The LPE performed at our institution was initiated by a nondirected donor who enabled the exchange for an ABO-incompatible pair, and the final recipient was selected from our deceased donor waitlist. The exchange was performed over the course of 2 consecutive days, and relied on the use and compliance of a bridge donor. Here, we show that LPE is feasible at centers with significant LDLT experience and affords an opportunity to expand LDLT in cases of ABO incompatibility or when nondirected donors arise. To our knowledge, this represents the first exchange of its kind in the United States.

Liver transplantation is a life-saving procedure for many patients. However, the number of liver transplants that can be performed is limited by donor organ availability. As with all scarce health resources, the overall objective is to ensure fair allocation of donor grafts. An ideal liver allocation model would consider the key ethical considerations of equity and utility, as well as fulfilling other requirements such as efficiency and transparency. Liver allocation has evolved to meet the growing problem of graft scarcity. An evidence-based approach to liver allocation is widely accepted, with an emphasis on objective measures to predict patient mortality. Need-based allocation (according to Model for End-stage Liver Disease score) is commonly practiced worldwide. However, utility, the expected gain from liver transplantation, is also an important consideration in liver allocation. The concept of transplant benefit balances both equity (need) and utility in allocation decisions. Transplant benefit is measured by the difference between a patient’s expected survival with and without transplantation. In the literature, transplant benefit is utilised both as an outcome (i.e. a metric of the gain from liver transplantation for an individual or group of patients with similar characteristics), and as a basis for liver allocation models. Transplant benefit-based allocation meets many requirements of an ideal liver allocation model, although there are challenges in creating accurate survival prediction models. The development of transplant benefit models and expected outcomes of transplant benefit-based allocation have not been investigated in the Australian and New Zealand (ANZ) context. Transplant benefit allocation models are not universally relevant due to differences in transplant populations and context. Two nationally-developed transplant benefit allocation models from US and UK populations demonstrated modest prediction performance in an Australian transplant popul

Split liver transplantation (SLT) is 1 strategy for maximizing the number of deceased donor liver transplants. Recent reports suggest that utilization of SLT in the United States remains low. We examined deceased donor offers that were ultimately split between 2010 and 2014. SLTs were categorized as "primary" and "secondary" transplants. We analyzed allocation patterns and used logistic regression to evaluate factors associated with secondary split discard. Four hundred eighteen livers were split: 54% from adult, 46% from pediatric donors. Of the 227 adult donor livers split, 61% met United Network for Organ Sharing "optimal" split criteria. A total of 770 recipients (418 primary and 352 secondary) were transplanted, indicating 16% discard. Ninety-two percent of the 418 primary recipients were children, and 47% were accepted on the first offer. Eighty-seven percent of the 352 secondary recipients were adults, and 7% were accepted on the first offer. Of the 352 pairs, 99% were transplanted in the same region, 36% at the same center. In logistic regression, shorter donor height was associated with secondary discard (odds ratio 0.97 per cm, 95% CI 0.94-1.00, P = .02). SLT volume by center was not predictive of secondary discard. Current policy proposals that incentivize SLT in the United States could increase the number of transplants to children and adults.

Functional impairment is associated with mortality in adult liver transplant candidates. This has not been studied in pediatric liver transplant candidates. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to investigate functional status, waitlist mortality, and posttransplant outcomes in children younger than 18 years who were waitlisted in 2006-2016 for primary liver transplant. Functional status was categorized, by using the Lansky Play-Performance Scale (LPPS), as normal/good (80-100), moderately impaired (50-70), or severely impaired (10-40) by center assessment. Among 3250 children not listed as Status 1A, 62% had an LPPS score of 80-100, 25% had a score of 50-70, and 13% had a score of 10-40 at listing. Children with an LPPS score of 10-40 at listing were more likely to die while on the waitlist (standardized hazard ratio 1.85, 95% confidence interval 1.09-3.13, P = .02) in analyses adjusting for being on a ventilator, breathing support, or dialysis and other illness severity measures. For the 2565 children transplanted, an LPPS score of 10-40 at listing drastically increased mortality risk by 1 year posttransplant (hazard ratio 5.77, 95% confidence interval 3.05-10.91, P < .0005). LPPS scores of 10-40 and 50-70 both increased the risk of graft loss by 1 year. Functional status is an independent predictor of waitlist and posttransplant mortality in pediatric liver transplant candidates. Validated tools for the assessment of functional status in these children would improve our ability to predict mortality risk-and to appropriately prioritize them for transplant.

To implement split liver transplantation (SLT) a mandatory-split policy has been adopted in Italy since August 2015: donors aged 18-50 years at standard risk are offered for SLT, resulting in a left-lateral segment (LLS) graft for children and an extended-right graft (ERG) for adults. We aim to analyze the impact of the new mandatory-split policy on liver transplantation (LT)-waiting list and SLT outcomes, compared to old allocation policy. Between August 2015 and December 2016 out of 413 potentially “splittable” donors, 252 (61%) were proposed for SLT, of whom 53 (21%) donors were accepted for SLT whereas 101 (40.1%) were excluded because of donor characteristics and 98 (38.9%) for absence of suitable pediatric recipients. The SLT rate augmented from 6% to 8.4%. Children undergoing SLT increased from 49.3% to 65.8% (P =.009) and the pediatric LT-waiting list time dropped (229 [10-2121] vs 80 [12-2503] days [P =.045]). The pediatric (4.5% vs 2.5% [P =.398]) and adult (9.7% to 5.2% [P <.001]) LT-waiting list mortality reduced; SLT outcomes remained stable. Retransplantation (HR = 2.641, P =.035) and recipient weight >20 kg (HR = 5.113, P =.048) in LLS, and ischemic time >8 hours (HR = 2.475, P =.048) in ERG were identified as predictors of graft failure. A national mandatory-split policy maximizes the SLT donor resources, whose selection criteria can be safely expanded, providing favorable impact on the pediatric LT-waiting list and priority for adult sick LT candidates.

To implement split liver transplantation (SLT) a mandatory-split policy has been adopted in Italy since August 2015: donors aged 18-50 years at standard risk are offered for SLT, resulting in a left-lateral segment (LLS) graft for children and an extended-right graft (ERG) for adults. We aim to analyze the impact of the new mandatory-split policy on liver transplantation (LT)-waiting list and SLT outcomes, compared to old allocation policy. Between August 2015 and December 2016 out of 413 potentially “splittable” donors, 252 (61%) were proposed for SLT, of whom 53 (21%) donors were accepted for SLT whereas 101 (40.1%) were excluded because of donor characteristics and 98 (38.9%) for absence of suitable pediatric recipients. The SLT rate augmented from 6% to 8.4%. Children undergoing SLT increased from 49.3% to 65.8% (P =.009) and the pediatric LT-waiting list time dropped (229 [10-2121] vs 80 [12-2503] days [P =.045]). The pediatric (4.5% vs 2.5% [P =.398]) and adult (9.7% to 5.2% [P <.001]) LT-waiting list mortality reduced; SLT outcomes remained stable. Retransplantation (HR = 2.641, P =.035) and recipient weight >20 kg (HR = 5.113, P =.048) in LLS, and ischemic time >8 hours (HR = 2.475, P =.048) in ERG were identified as predictors of graft failure. A national mandatory-split policy maximizes the SLT donor resources, whose selection criteria can be safely expanded, providing favorable impact on the pediatric LT-waiting list and priority for adult sick LT candidates.

Since its evolution, organ allocation in liver transplantation has been based upon the ‘rule of rescue’, where patients are prioritized for transplantation based on their medical need and acuity. As the system has evolved, arbitrary geographic boundaries and variations in the supply and demand for organs have created a system marked by geographic inequities. Share 35, the most recent of the United Network for Organ Sharing liver transplant allocation policies, aimed to reduce these inequities at the regional level by instituting intra-regional organ sharing for the sickest patients (defined as allocation Model for End Stage Liver Disease (MELD) scores of ≥35). Similar to other organ allocation policies, evaluations of Share 35 have been limited to traditional markers of quality in transplantation, namely pre- and post-transplant survival. Acknowledging that these policies have far reaching effects, beyond patient survival alone, this dissertation assessed the potential impacts of the Share 35 policy on both inpatient utilization and post-transplant disability. Utilizing a novel database linkage between six state inpatient datasets (Agency for Healthcare Research and Quality – Healthcare Cost and Utilization Project and California Office for Statewide Hospital Planning and Development) and the liver transplant registry, a stepwise analysis of the potential causal pathways through which the policy may have affected each outcome was completed. Prior to assessing the impact of Share 35 directly, potential drivers of post-transplant utilization prior to policy implementation were evaluated, indicating that both patient acuity at the time of transplant and donor organ quality are strongly associated with post-transplantation inpatient utilization within the six months following transplantation. These findings build upon previous single-institution studies and prior reports which were limited to only 30-days of post-transplant follow-up. This dissertation then assesses Sha

Since its evolution, organ allocation in liver transplantation has been based upon the ‘rule of rescue’, where patients are prioritized for transplantation based on their medical need and acuity. As the system has evolved, arbitrary geographic boundaries and variations in the supply and demand for organs have created a system marked by geographic inequities. Share 35, the most recent of the United Network for Organ Sharing liver transplant allocation policies, aimed to reduce these inequities at the regional level by instituting intra-regional organ sharing for the sickest patients (defined as allocation Model for End Stage Liver Disease (MELD) scores of ≥35). Similar to other organ allocation policies, evaluations of Share 35 have been limited to traditional markers of quality in transplantation, namely pre- and post-transplant survival. Acknowledging that these policies have far reaching effects, beyond patient survival alone, this dissertation assessed the potential impacts of the Share 35 policy on both inpatient utilization and post-transplant disability. Utilizing a novel database linkage between six state inpatient datasets (Agency for Healthcare Research and Quality – Healthcare Cost and Utilization Project and California Office for Statewide Hospital Planning and Development) and the liver transplant registry, a stepwise analysis of the potential causal pathways through which the policy may have affected each outcome was completed. Prior to assessing the impact of Share 35 directly, potential drivers of post-transplant utilization prior to policy implementation were evaluated, indicating that both patient acuity at the time of transplant and donor organ quality are strongly associated with post-transplantation inpatient utilization within the six months following transplantation. These findings build upon previous single-institution studies and prior reports which were limited to only 30-days of post-transplant follow-up. This dissertation then assesses Sha

Since its evolution, organ allocation in liver transplantation has been based upon the ‘rule of rescue’, where patients are prioritized for transplantation based on their medical need and acuity. As the system has evolved, arbitrary geographic boundaries and variations in the supply and demand for organs have created a system marked by geographic inequities. Share 35, the most recent of the United Network for Organ Sharing liver transplant allocation policies, aimed to reduce these inequities at the regional level by instituting intra-regional organ sharing for the sickest patients (defined as allocation Model for End Stage Liver Disease (MELD) scores of ≥35). Similar to other organ allocation policies, evaluations of Share 35 have been limited to traditional markers of quality in transplantation, namely pre- and post-transplant survival. Acknowledging that these policies have far reaching effects, beyond patient survival alone, this dissertation assessed the potential impacts of the Share 35 policy on both inpatient utilization and post-transplant disability. Utilizing a novel database linkage between six state inpatient datasets (Agency for Healthcare Research and Quality – Healthcare Cost and Utilization Project and California Office for Statewide Hospital Planning and Development) and the liver transplant registry, a stepwise analysis of the potential causal pathways through which the policy may have affected each outcome was completed. Prior to assessing the impact of Share 35 directly, potential drivers of post-transplant utilization prior to policy implementation were evaluated, indicating that both patient acuity at the time of transplant and donor organ quality are strongly associated with post-transplantation inpatient utilization within the six months following transplantation. These findings build upon previous single-institution studies and prior reports which were limited to only 30-days of post-transplant follow-up. This dissertation then assesses Sha

The impact of a new national kidney allocation system (KAS) on access to the national deceased-donor waiting list (waitlisting) and racial/ethnic disparities in waitlisting among US end-stage renal disease (ESRD) patients is unknown. We examined waitlisting pre- and post-KAS among incident (N = 1 253 100) and prevalent (N = 1 556 954) ESRD patients from the United States Renal Data System database (2005-2015) using multivariable time-dependent Cox and interrupted time-series models. The adjusted waitlisting rate among incident patients was 9% lower post-KAS (hazard ratio [HR]: 0.91; 95% confidence interval [CI], 0.90-0.93), although preemptive waitlisting increased from 30.2% to 35.1% (P < .0001). The waitlisting decrease is largely due to a decline in inactively waitlisted patients. Pre-KAS, blacks had a 19% lower waitlisting rate vs whites (HR: 0.81; 95% CI, 0.80-0.82); following KAS, disparity declined to 12% (HR: 0.88; 95% CI, 0.85-0.90). In adjusted time-series analyses of prevalent patients, waitlisting rates declined by 3.45/10 000 per month post-KAS (P < .001), resulting in ≈146 fewer waitlisting events/month. Shorter dialysis vintage was associated with greater decreases in waitlisting post-KAS (P < .001). Racial disparity reduction was due in part to a steeper decline in inactive waitlisting among minorities and a greater proportion of actively waitlisted minority patients. Waitlisting and racial disparity in waitlisting declined post-KAS; however, disparity remains.

Under the U.S. Lung Allocation Score (LAS) system, older and sicker patients are prioritized for lung transplantation (LT). The impact of these changes on health-related quality of life (HRQL) after transplant has not been determined. In a single-center prospective cohort study from 2010 to 2016, we assessed HRQL before and repeatedly after LT for up to 3 years using the SF12-Physical and Mental Health, the respiratory-specific Airway Questionnaire 20-Revised, and the Euroqol 5D/Visual Analog Scale utility measures by multivariate linear mixed models jointly modeled with death. We also tested changes in LT-Valued Life Activities disability, BMI, allograft function, and 6-min walk test exercise capacity as predictors of HRQL change. Among 211 initial participants (92% of those eligible), LT improved HRQL by all 5 measures (p < 0.05) and all but SF12-Mental Health improved by threefold or greater than the minimally clinically important difference. Compared to younger participants, those aged ≥65 improved less in SF12-Physical and Mental Health (p < 0.01). Improvements in disability accounted for much of the HRQL improvement. In the LAS era, LT affords meaningful and durable HRQL improvements, mediated by amelioration of disability. Identifying factors limiting HRQL improvement in selected subgroups, especially those aged ≥65, are needed to maximize the net benefits of LT.

Nonstandard exception requests (NSERs), for which transplant centers provide patient-specific narratives to support a higher Model for End-stage Liver Disease/Pediatric End-stage Liver Disease score, are made for >30% of pediatric liver transplant candidates. We describe the justifications used in pediatric NSER narratives 2009-2014 and identify justifications associated with NSER denial, waitlist mortality, and transplant. Using United Network for Organ Sharing data, 1272 NSER narratives from 1138 children with NSERs were coded for analysis. The most common NSER justifications were failure-to-thrive (48%) and risk of death (40%); both associated with approval. Varices, involvement of another organ, impaired quality of life, and encephalopathy were justifications used more often in denied NSERs. Of the 25 most prevalent justifications, 60% were not associated with approval or denial. Waitlist mortality risk was increased when fluid overload or "posttransplant complication outside standard criteria" were cited and decreased when liver-related infection was noted. Transplant probability was increased when the narrative mentioned liver-related infections, and fluid overload for children <2 years old; it decreased when "posttransplant complications outside standard criteria" and primary sclerosing cholangitis were cited. This analysis provides novel insight and suggests targets for future consideration in outcomes research and exception criteria. Changes in the allocation system are needed to ensure equity and optimize outcomes for all pediatric candidates.

From 5000 to 10 000 kidney patients die prematurely in the United States each year, and about 100 000 more suffer the debilitating effects of dialysis, because of a shortage of transplant kidneys. To reduce this shortage, many advocate having the government compensate kidney donors. This paper presents a comprehensive cost-benefit analysis of such a change. It considers not only the substantial savings to society because kidney recipients would no longer need expensive dialysis treatments--$1.45 million per kidney recipient--but also estimates the monetary value of the longer and healthier lives that kidney recipients enjoy--about $1.3 million per recipient. These numbers dwarf the proposed $45 000-per-kidney compensation that might be needed to end the kidney shortage and eliminate the kidney transplant waiting list. From the viewpoint of society, the net benefit from saving thousands of lives each year and reducing the suffering of 100 000 more receiving dialysis would be about $46 billion per year, with the benefits exceeding the costs by a factor of 3. In addition, it would save taxpayers about $12 billion each year.

From 5000 to 10 000 kidney patients die prematurely in the United States each year, and about 100 000 more suffer the debilitating effects of dialysis, because of a shortage of transplant kidneys. To reduce this shortage, many advocate having the government compensate kidney donors. This paper presents a comprehensive cost-benefit analysis of such a change. It considers not only the substantial savings to society because kidney recipients would no longer need expensive dialysis treatments--$1.45 million per kidney recipient--but also estimates the monetary value of the longer and healthier lives that kidney recipients enjoy--about $1.3 million per recipient. These numbers dwarf the proposed $45 000-per-kidney compensation that might be needed to end the kidney shortage and eliminate the kidney transplant waiting list. From the viewpoint of society, the net benefit from saving thousands of lives each year and reducing the suffering of 100 000 more receiving dialysis would be about $46 billion per year, with the benefits exceeding the costs by a factor of 3. In addition, it would save taxpayers about $12 billion each year.

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.

Neutralizing antibodies (NAbs) form the basis of immunotherapeutic strategies against many important human viral infections. Accordingly, we studied the prevalence, titer, genotype-specificity, and mechanism of action of anti-polyomavirus BK (BKV) NAbs in commercially available human immune globulin (IG) preparations designed for intravenous (IV) use. Pseudovirions (PsV) of genotypes Ia, Ib2, Ic, II, III, and IV were generated by co-transfecting a reporter plasmid encoding luciferase and expression plasmids containing synthetic codon-modified VP1, VP2, and VP3 capsid protein genes into 293TT cells. NAbs were measured using luminometry. All IG preparations neutralized all BKV genotypes, with mean EC50 titers as high as 254 899 for genotype Ia and 6,666 for genotype IV. Neutralizing titers against genotypes II and III were higher than expected, adding to growing evidence that infections with these genotypes are more common than currently appreciated. Batch to batch variation in different lots of IG was within the limits of experimental error. Antibody mediated virus neutralizing was dose dependent, modestly enhanced by complement, genotype-specific, and achieved without effect on viral aggregation, capsid morphology, elution, or host cell release. IG contains potent NAbs capable of neutralizing all major BKV genotypes. Clinical trials based on sound pharmacokinetic principles are needed to explore prophylactic and therapeutic applications of these anti-viral effects, until effective small molecule inhibitors of BKV replication can be developed.

Since Italian liver allocation policy was last revised (in 2012), relevant critical issues and conceptual advances have emerged, calling for significant improvements. We report the results of a national consensus conference process, promoted by the Italian College of Liver Transplant Surgeons (for the Italian Society for Organ Transplantation) and the Italian Association for the Study of the Liver, to review the best indicators for orienting organ allocation policies based on principles of urgency, utility, and transplant benefit in the light of current scientific evidence. MELD exceptions and hepatocellular carcinoma were analyzed to construct a transplantation priority algorithm, given the inequity of a purely MELD-based system for governing organ allocation. Working groups of transplant surgeons and hepatologists prepared a list of statements for each topic, scoring their quality of evidence and strength of recommendation using the Centers for Disease Control grading system. A jury of Italian transplant surgeons, hepatologists, intensivists, infectious disease specialists, epidemiologists, representatives of patients' associations and organ-sharing organizations, transplant coordinators, and ethicists voted on and validated the proposed statements. After carefully reviewing the statements, a critical proposal for revising Italy's current liver allocation policy was prepared jointly by transplant surgeons and hepatologists.

Background & Aims: The model for end-stage liver disease (MELD) is used for organ allocation in liver transplantation (LT), but its prognostic performance is less accurate in patients with low score. We assess the outcome of patients with MELD < 18 awaiting LT, finding prognostic variables to identify a high dropout risk. Methods: Training set consisted of 277 patients and validation cohort of 292 patients. Competing risk regression analysis, taking into account LT, was used for univariate/multivariate analysis. Results: Ascites, sodium, bilirubin, albumin and glomerular filtration rate were independently associated with a 12-month dropout risk in the training set. Combining these five prognostic parameters, we calculated a new score named liver-renal-risk (LIRER). In the validation set, the 12-month LIRER concordance index showed a discrimination power [0.798, 95% confidence interval (95% CI) 0.793-0.803] better than MELD (0.582, 95% CI 0.575-0.588), Child-Turcotte-Pugh (0.687, 95% CI 0.681-0.693), MELD-sodium (0.721, 95% CI 0.715-0.727) and MELD-ascites-sodium (0.729, 95% CI 0.724-0.735), with a remarkable calibration (Hosmer-Lemeshow test: P = 0.91; R2 = 0.911). Considering all study patients, the risk of wait list dropout increased with the rise in LIRER. The survival benefit analysis comparing the wait list dropout risk with the mortality of the 216 transplanted patients with same LIRER showed an important benefit for LT in patients with LIRER > 15.9. Conclusions: In patients with low MELD (<18), combination of ascites, sodium, albumin, bilirubin and renal function in a new score (LIRER) discriminates patients at high risk of medium-term adverse outcome from those in whom LT may be safely deferred.

The increase in organ demand for liver transplantation has exceeded the supply, resulting in longer waiting periods and higher death rates on the waiting list. As a consequence, most liver transplant centers throughout US and Europe have resorted to using suboptimal donors to expand the donor pool. The most recent papers have reported that the percentage of HCV(+) recipients who are transplanted with HCV(+) donors is more than 10∈% of cases. In the near future, it is expected that a larger number of HCV(+) liver transplant candidates will be offered an HCV(+) graft. This means that greater experience on the management of both HCV infection and fibrosis progression will be requested from the transplant hepatologist. At the same time, since the rate of donation has reached a plateau since 2006, it is probable that older donors and grafts with mild-to-moderate steatosis will be used. There is growing evidence showing that the outcome of HCV(+) recipients is not different whether they receive an HCV(+) or an HCV(-) graft in terms of graft and patient survival. However, it is mandatory that liver biopsies of HCV(+) donors must show minimal or likely no fibrosis and minimal inflammation in order to be used for grafting. In this new scenario, the adequacy of the match between donor and recipient may be paramount since a decreased survival might be expected in high-risk patients receiving organs from suboptimal donors. In HCV(+) recipients from HCV(+) donors we should ensure an accepted graft and patient survival with no excessive costs for the transplant community. The benefit of liver transplantation should be evaluated in this subset of the population.

BACKGROUND: Shipment of organs during the allocation process aims to improve human leucocyte antigen (HLA) matching but can also have a detrimental effect by prolonging cold ischaemia. The overall effect of organ exchange on post-transplant outcomes in the Eurotransplant (ET) region has not been investigated.METHODS: This is a retrospective single-centre cohort study to investigate the effect of shipment of renal allografts on cold ischaemia times and the incidence of acute rejection (AR) and graft survival in 661 transplantations of deceased donor kidneys.RESULTS: Forty-six per cent (N = 301) of the patients received a locally procured and 54% (N = 360) a shipped donor kidney. Locally procured donors tended to be older, more often hypertensive and had less frequently died from trauma. Recipients of shipped kidneys were at higher immunological risk, being younger, more frequently retransplanted and immunized against HLA antigens. Shipped kidneys had a 2.2-h prolongation of cold ischaemia time (18.0 versus 20.2 h; P < 0.0001) but significantly less HLA A, B and DR mismatches (2.20 versus 2.84; P < 0.0001). Recipients of shipped kidneys had an increased incidence of first-year AR [19 versus 13%; odds ratio 1.62 (1.06-2.49); P = 0.026] and death-censored graft loss [hazard ratio 1.6 (1.1-2.4); P = 0.01] that was no longer statistically significant after adjustments for risk factors by multivariable modelling.CONCLUSIONS: Shipment of kidneys in the ET region is associated with a modest increase in cold ischaemia time and significantly better HLA matching. This allows for successful transplantation of higher risk patients with no significant penalty with regard to AR rates or death-censored graft survival., JOURNAL ARTICLE, SCOPUS: ar.j, info:eu-repo/semantics/published

Kidney transplant and liver transplant are the treatments of choice for patients with end-stage renal disease and end-stage liver disease, respectively. Pancreas transplant is most commonly performed along with kidney transplant in diabetic end-stage renal disease patients. Despite a steady increase in the numbers of kidney and liver transplants performed each year in the United States, a significant shortage of kidneys and livers available for transplant remains. Organ allocation is the process the Organ Procurement and Transplantation Network (OPTN) uses to determine which candidates are offered which deceased donor organs. OPTN is charged with ensuring the effectiveness, efficiency and equity of organ sharing in the national system of organ allocation. The policy has changed incrementally over time in efforts to optimize allocation to meet these often competing goals. This review describes the history, current status and future direction of policies regarding the allocation of abdominal organs for transplant, namely the kidney, liver and pancreas, in the United States.

BACKGROUND: Shipment of organs during the allocation process aims to improve human leucocyte antigen (HLA) matching but can also have a detrimental effect by prolonging cold ischaemia. The overall effect of organ exchange on post-transplant outcomes in the Eurotransplant (ET) region has not been investigated.METHODS: This is a retrospective single-centre cohort study to investigate the effect of shipment of renal allografts on cold ischaemia times and the incidence of acute rejection (AR) and graft survival in 661 transplantations of deceased donor kidneys.RESULTS: Forty-six per cent (N = 301) of the patients received a locally procured and 54% (N = 360) a shipped donor kidney. Locally procured donors tended to be older, more often hypertensive and had less frequently died from trauma. Recipients of shipped kidneys were at higher immunological risk, being younger, more frequently retransplanted and immunized against HLA antigens. Shipped kidneys had a 2.2-h prolongation of cold ischaemia time (18.0 versus 20.2 h; P < 0.0001) but significantly less HLA A, B and DR mismatches (2.20 versus 2.84; P < 0.0001). Recipients of shipped kidneys had an increased incidence of first-year AR [19 versus 13%; odds ratio 1.62 (1.06-2.49); P = 0.026] and death-censored graft loss [hazard ratio 1.6 (1.1-2.4); P = 0.01] that was no longer statistically significant after adjustments for risk factors by multivariable modelling.CONCLUSIONS: Shipment of kidneys in the ET region is associated with a modest increase in cold ischaemia time and significantly better HLA matching. This allows for successful transplantation of higher risk patients with no significant penalty with regard to AR rates or death-censored graft survival., JOURNAL ARTICLE, SCOPUS: ar.j, info:eu-repo/semantics/published

Better tools for predicting the risk of death while awaiting transplantation are urgently needed because organ shortage is increasing the numbers on transplantation waiting lists. The aminopyrine breath test (ABT), model for end-stage liver disease (MELD), and Child-Pugh (C-P) score were compared as predictors of this risk in 137 cirrhotic candidates for liver transplantation. Eighty-three were transplanted within 3 months of registration, 35 others survived, 13 died before transplantation, and 6 were removed from the list. By univariate analysis, the continuous variables significantly associated with death while awaiting transplantation were: history of infected ascites, C-P score, ABT, and international normalized ratio or prothrombin time. Receiver operating characteristic curves for quantitative variables showed that the area under the curve was greatest for ABT (0.858 +/- 0.067). By Youden curve analysis, the best cut-off points for identifying cirrhotic patients at high risk of death while on the waiting list were: > 10, > 16, and < 0.7% for the C-P score, MELD score, and ABT, respectively. These results show that ABT is as good as the MELD and C-P scores, or better, as a predictor of death among cirrhotic patients awaiting liver transplantation., SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

Better tools for predicting the risk of death while awaiting transplantation are urgently needed because organ shortage is increasing the numbers on transplantation waiting lists. The aminopyrine breath test (ABT), model for end-stage liver disease (MELD), and Child-Pugh (C-P) score were compared as predictors of this risk in 137 cirrhotic candidates for liver transplantation. Eighty-three were transplanted within 3 months of registration, 35 others survived, 13 died before transplantation, and 6 were removed from the list. By univariate analysis, the continuous variables significantly associated with death while awaiting transplantation were: history of infected ascites, C-P score, ABT, and international normalized ratio or prothrombin time. Receiver operating characteristic curves for quantitative variables showed that the area under the curve was greatest for ABT (0.858 +/- 0.067). By Youden curve analysis, the best cut-off points for identifying cirrhotic patients at high risk of death while on the waiting list were: > 10, > 16, and < 0.7% for the C-P score, MELD score, and ABT, respectively. These results show that ABT is as good as the MELD and C-P scores, or better, as a predictor of death among cirrhotic patients awaiting liver transplantation., SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published