Complications and Their Resolution in Recipients of Deceased and Living Donor Liver Transplants: Findings From the A2ALL Cohort Study.

The purpose of this study was to explore long-term complications in recipients of deceased donor liver transplant (DDLT) and living donor liver transplant (LDLT) in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). We analyzed 471 DDLTs and 565 LDLTs from 1998 to 2010 that were followed up to 10 years for 36 categories of complications. Probabilities of complications and their resolutions were estimated using the Kaplan-Meier method, and predictors were tested in Cox proportional hazards models. Median follow-up for DDLT and LDLT was 4.19 and 4.80 years, respectively. DDLT recipients were more likely to have hepatocellular carcinoma and higher disease severity, including Model for End-Stage Liver Disease score. Complications occurring with higher probability in LDLT included biliary-related complications and hepatic artery thrombosis. In DDLT, ascites, intra-abdominal bleeding, cardiac complications and pulmonary edema were significantly more probable. Development of chronic kidney disease stage 4 or 5 was less likely in LDLT recipients (hazard ratio [HR] 0.41, p = 0.02). DDLT and LDLT had similar risk of grade 4 complications (HR 0.89, p = 0.60), adjusted for other risk factors. Once a complication occurred, the time to resolution did not differ between LDLT and DDLT. Future efforts should be directed toward reducing the occurrence of complications after liver transplantation.

Morbidity and mortality of live lung donation: results from the RELIVE study.

The Renal and Lung Living Donors Evaluation Study assesses outcomes of live lung (lobectomy) donors. This is a retrospective cohort study at University of Southern California (USC) and Washington University (WASHU) Medical Centers (1993­2006), using medical records to assess morbidity and national databases to ascertain postdonation survival and lung transplantation. Serious complications were defined as those that required significant treatment, were potentially life-threatening or led to prolonged hospitalization. The 369 live lung donors (287 USC, 82 WASHU) were predominantly white, non-Hispanic and male; 72% had a biological relationship to the recipient, and 30% were recipient parents. Serious complications occurred in 18% of donors; 2.2% underwent reoperation and 6.5% had an early rehospitalization. The two centers had significantly different incidences of serious complications (p < 0.001). No deaths occurred and no donors underwent lung transplantation during 4000+ person-years of follow-up (death: minimum 4, maximum 17 years; transplant: minimum 5, maximum 19). Live lung donation remains a potential option for recipients when using deceased donor lungs lacks feasibility. However, the use of two live donors for each recipient and the risk of morbidity associated with live lung donation do not justify this approach when deceased lung donors remain available. Center effects and long-term live donor outcomes require further evaluation.

Health-related quality of life in kidney donors from the last five decades: results from the RELIVE study.

Live donation benefits recipients, but the long-term consequences for donors remain uncertain. Renal and Lung Living Donors Evaluation Study surveyed kidney donors (N = 2455; 61% women; mean age 58, aged 24-94; mean time from donation 17 years, range 5-48 years) using the Short Form-36 Health Survey (SF-36). The 95% confidence intervals for White and African-American donors included or exceeded SF-36 norms. Over 80% of donors reported average or above average health for their age and sex (p < 0.0001). Donors' age-sex adjusted physical component summary (PCS) scores declined by half a point each decade after donation (p = 0.0027); there was no decline in mental component summary (MCS) scores. White donors' PCS scores were three points higher (p = 0.0004) than non-Whites'; this difference remained constant over time. Nine percent of donors had impaired health (PCS or MCS score >1 SD below norm). Obesity, history of psychiatric difficulties and non-White race were risk factors for impaired physical health; history of psychiatric difficulties was a risk factor for impaired mental health. Education, older donation age and a first-degree relation to the recipient were protective factors. One percent reported that donation affected their health very negatively. Enhanced predonation evaluation and counseling may be warranted, along with ongoing monitoring for overweight donors.

Demographic, metabolic, and blood pressure characteristics of living kidney donors spanning five decades.

While cautious criteria for selection of living kidney donors are credited for favorable outcomes, recent practice changes may include acceptance of less than ideal donors. To characterize trends in donor acceptance, the Renal and Lung Living Donors Evaluation (RELIVE) Study evaluated 8,951 kidney donors who donated between 1963 and 2007 at three major U.S. transplant centers. Over the study interval, there was an increase in the percentage of donors >40 years old from 38% to 51%; donors >60 years varied between 1% and 4%. The proportion of donors with obesity increased from 8% to 26% and with glucose intolerance from 9% to 25%. The percentage of hypertensive donors was consistent (5-8%). Accepted donors ≥60 years old were more likely to have obesity, glucose intolerance, and/or hypertension compared to younger donors (p<0.0001). Our results demonstrate important trends in acceptance of older and more obese donors. The fraction of older donors accepted with glucose intolerance or hypertension remains small and for the majority includes mild elevations in glucose or blood pressure that were previously classified as within normal limits.

Predictors of liver donation without kidney recovery in a cohort of expanded criteria donors: identifying opportunities to improve expanded criteria donor kidney utilization.

To maximize deceased donation, it is necessary to facilitate organ recovery from expanded criteria donors (ECDs). Utilization of donors meeting the kidney definition for ECDs increases access to kidney transplantation and reduces waiting times; however, ECDs often do not proceed to kidney recovery. Based on a prospective study of three Organ Procurement Organizations in the United States, we describe the characteristics of donors meeting the Organ Procurement and Transplant Network (OPTN) ECD kidney definition (donor age 60+ or donor age 50-60 years with two of the following: final serum creatinine > 1.5 mg/dL, history of hypertension, or death from cerebral vascular accident) who donated a liver without kidney recovery. ECDs with organs recovered between February 2003 and September 2005 by New England Organ Bank, Gift of Life Michigan, and LifeChoice Donor Services were studied (n = 324). All donors were declared dead by neurological criteria. Data on a wide range of donor characteristics were collected, including donor demographics, medical history, cause of death, donor status during hospitalization, serological status, and donor kidney quality. Logistic regression models were used to identify donor characteristics predictive of liver-alone donation. Seventy-four of the 324 donors fulfilling the ECD definition for kidneys donated a liver alone (23%). History of diabetes, final serum creatinine > 1.5 mg/dL, age 70+, and presence of proteinuria were associated with liver-alone donation in univariate models. On multivariate analysis, only final serum creatinine > 1.5 mg/dL and age 70+ were independently predictive of liver donation alone. Older age and elevated serum creatinine may be perceived as stronger contraindications to kidney donation than the remaining elements of the ECD definition. It is likely that at least a proportion of these liver-alone donors represent missed opportunities for kidney transplantation.

Utilization of kidneys with similar kidney donor risk index values from standard versus expanded criteria donors.

With the shortage of standard criteria donor (SCD) kidneys, efficient expanded criteria donor (ECD) kidney utilization has become more vital. We investigated the effects of the ECD label on kidney recovery, utilization and outcomes. Using data from the Scientific Registry of Transplant Recipients from November 2002 to May 2010, we determined recovery and transplant rates, and modeled discard risk, for kidneys within a range of kidney donor risk index (KDRI) 1.4-2.1 that included both SCD and ECD kidneys. To further compare similar quality kidneys, these kidneys were again divided into three KDRI intervals. Overall, ECD kidneys had higher recovery rates, but lower transplant rates. However, within each KDRI interval, SCD and ECD kidneys were transplanted at similar rates. Overall, there was increased risk for discard for biopsied kidneys. SCD kidneys in the lower two KDRI intervals had the highest risk of discard if biopsied. Pumped kidneys had a lower risk of discard, which was modulated by KDRI for SCD kidneys but not ECD kidneys. Although overall ECD graft survival was worse than SCD, there were no differences within individual KDRI intervals. Thus, ECD designation adversely affects neither utilization nor outcomes beyond that predicted by KDRI.

Complications of living donor hepatic lobectomy--a comprehensive report.

A wider application of living donor liver transplantation is limited by donor morbidity concerns. An observational cohort of 760 living donors accepted for surgery and enrolled in the Adult-to-Adult Living Donor Liver Transplantation cohort study provides a comprehensive assessment of incidence, severity and natural history of living liver donation (LLD) complications. Donor morbidity (assessed by 29 specific complications), predictors, time from donation to complications and time from complication onset to resolution were measured outcomes over a 12-year period. Out of the 760 donor procedures, 20 were aborted and 740 were completed. Forty percent of donors had complications (557 complications among 296 donors), mostly Clavien grades 1 and 2. Most severe counted by complication category; grade 1 (minor, n = 232); grade 2 (possibly life-threatening, n = 269); grade 3 (residual disability, n = 5) and grade 4 (leading to death, n = 3). Hernias (7%) and psychological complications (3%) occurred >1 year postdonation. Complications risk increased with transfusion requirement, intraoperative hypotension and predonation serum bilirubin, but did not decline with the increased center experience with LLD. The probability of complication resolution within 1 year was overall 95%, but only 75% for hernias and 42% for psychological complications. This report comprehensively quantifies LLD complication risk and should inform decision making by potential donors and their caregivers.

Impact of MELD-based allocation on end-stage renal disease after liver transplantation.

The proportion of patients undergoing liver transplantation (LT), with concomitant renal dysfunction, markedly increased after allocation by the model for end-stage liver disease (MELD) score was introduced. We examined the incidence of subsequent post-LT end-stage renal disease (ESRD) before and after the policy was implemented. Data on all adult deceased donor LT recipients between April 27, 1995 and December 31, 2008 (n = 59 242), from the Scientific Registry of Transplant Recipients, were linked with Centers for Medicare & Medicaid Services' ESRD data. Cox regression was used to (i) compare pre-MELD and MELD eras with respect to post-LT ESRD incidence, (ii) determine the risk factors for post-LT ESRD and (iii) quantify the association between ESRD incidence and mortality. Crude rates of post-LT ESRD were 12.8 and 14.5 per 1000 patient-years in the pre-MELD and MELD eras, respectively. Covariate-adjusted post-LT ESRD risk was higher in the MELD era (hazard ratio [HR]= 1.15; p = 0.0049). African American race, hepatitis C, pre-LT diabetes, higher creatinine, lower albumin, lower bilirubin and sodium >141 mmol/L at LT were also significant predictors of post-LT ESRD. Post-LT ESRD was associated with higher post-LT mortality (HR = 3.32; p < 0.0001). The risk of post-LT ESRD, a strong predictor of post-LT mortality, is 15% higher in the MELD era. This study identified potentially modifiable risk factors of post-LT ESRD. Early intervention and modification of these risk factors may reduce the burden of post-LT ESRD.

Sex-based disparities in liver transplant rates in the United States.

We sought to characterize sex-based differences in access to deceased donor liver transplantation. Scientific Registry of Transplant Recipients data were used to analyze n = 78 998 adult candidates listed before (8/1997-2/2002) or after (2/2002-2/2007) implementation of Model for End-Stage Liver Disease (MELD)-based liver allocation. The primary outcome was deceased donor liver transplantation. Cox regression was used to estimate covariate-adjusted differences in transplant rates by sex. Females represented 38% of listed patients in the pre-MELD era and 35% in the MELD era. Females had significantly lower covariate-adjusted transplant rates in the pre-MELD era (by 9%; p < 0.0001) and in the MELD era (by 14%; p < 0.0001). In the MELD era, the disparity in transplant rate for females increased as waiting list mortality risk increased, particularly for MELD scores ≥15. Substantial geographic variation in sex-based differences in transplant rates was observed. Some areas of the United States had more than a 30% lower covariate-adjusted transplant rate for females compared to males in the MELD era. In conclusion, the disparity in liver transplant rates between females and males has increased in the MELD era. It is especially troubling that the disparity is magnified among patients with high MELD scores and in certain regions of the United States.

The economic implications of broader sharing of liver allografts.

Liver transplantation has evolved over the past four decades into the most effective method to treat end-stage liver failure and one of the most expensive medical technologies available. Accurate understanding of the financial implication of recipient severity of illness is crucial to assessing the economic impact of allocation policies. A novel database of linked clinical data from the Organ Procurement and Transplantation Network with cost accounting data from the University HealthSystem Consortium was used to analyze liver transplant costs for 15,813 liver transplants. This data was then utilized to consider the economic impact of alternative allocation systems designed to increase sharing of liver allografts using simulation results. Transplant costs were strongly associated with recipient severity of illness as assessed by the MELD score (p < 0.0001); however, this relationship was not linear. Simulation analysis of the reallocation of livers from low MELD patients to high MELD using a two-tiered regional sharing approach (MELD 15/25) resulted in 88 fewer deaths annually at estimated cost of $17,056 per quality-adjusted life-year saved. The results suggest that broader sharing of liver allografts offers a cost-effective strategy to reduce the mortality from end stage liver disease.

Transplant surgery fellow perceptions about training and the ensuing job market-are the right number of surgeons being trained?

The American Society of Transplant Surgeons (ASTS) sought whether the right number of abdominal organ transplant surgeons are being trained in the United States. Data regarding fellowship training and the ensuing job market were obtained by surveying program directors and fellowship graduates from 2003 to 2005. Sixty-four ASTS-approved programs were surveyed, representing 139 fellowship positions in kidney, pancreas and/or liver transplantation. One-quarter of programs did not fill their positions. Forty-five fellows graduated annually. Most were male (86%), aged 31-35 years (57%), married (75%) and parents (62%). Upon graduation, 12% did not find transplant jobs (including 8% of Americans/Canadians), 14% did not get jobs for transplanting their preferred organ(s), 11% wished they focused more on transplantation and 27% changed jobs early. Half fellows were international medical graduates; 45% found US/Canadian transplant jobs, particularly 73% with US/Canadian residency training. Fellows reported adequate exposure to training volume, candidate selection, pre/postoperative care and organ procurement, but not to donor management/selection, outpatient care and core didactics. One-sixth noted insufficient 'mentoring/preparation for a transplantation career'. Currently, there seem to be enough trainees to fill entry-level positions. One-third program directors believe that there are too many trainees, given the current and foreseeable job market. ASTS is assessing the total workforce of transplant surgeons and evolving manpower needs.

Donation after cardiac death liver transplantation: predictors of outcome.

We aimed to identify recipient, donor and transplant risk factors associated with graft failure and patient mortality following donation after cardiac death (DCD) liver transplantation. These estimates were derived from Scientific Registry of Transplant Recipients data from all US liver-only DCD recipients between September 1, 2001 and April 30, 2009 (n = 1567) and Cox regression techniques. Three years post-DCD liver transplant, 64.9% of recipients were alive with functioning grafts, 13.6% required retransplant and 21.6% died. Significant recipient factors predictive of graft failure included: age ≥ 55 years, male sex, African-American race, HCV positivity, metabolic liver disorder, transplant MELD ≥ 35, hospitalization at transplant and the need for life support at transplant (all, p ≤ 0.05). Donor characteristics included age ≥ 50 years and weight >100 kg (all, p ≤ 0.005). Each hour increase in cold ischemia time (CIT) was associated with 6% higher graft failure rate (HR 1.06, p < 0.001). Donor warm ischemia time ≥ 35 min significantly increased graft failure rates (HR 1.84, p = 0.002). Recipient predictors of mortality were age ≥ 55 years, hospitalization at transplant and retransplantation (all, p ≤ 0.006). Donor weight >100 kg and CIT also increased patient mortality (all, p ≤ 0.035). These findings are useful for transplant surgeons creating DCD liver acceptance protocols.

Foreigners traveling to the U.S. for transplantation may adversely affect organ donation: a national survey.

The aims of this study were (1) to determine attitudes among the American public regarding foreigners coming to the United States for the purposes of transplantation, and (2) to investigate the impact this practice might have on the public's willingness to donate organs. A probability-based national sample of adults age > or =18 was asked whether people should be allowed to travel to the United States to receive a transplant, and whether this practice would discourage the respondents from becoming an organ donor. Among 1049 participants, 30% (95% CI 25-34%) felt that people should not be allowed to travel to the United States to receive a deceased donor transplant, whereas 28% felt this would be acceptable in some cases. Thirty-eight percent (95% CI 33-42%) indicated that this practice might prevent them from becoming an organ donor. In conclusion, deceased-donor transplantation of foreigners is opposed by many Americans. Media coverage of this practice has the potential to adversely affect organ donation.

Database comparison of the adult-to-adult living donor liver transplantation cohort study (A2ALL) and the SRTR U.S. Transplant Registry.

Data submitted by transplant programs to the Organ Procurement and Transplantation Network (OPTN) are used by the Scientific Registry of Transplant Recipients (SRTR) for policy development, performance evaluation and research. This study compared OPTN/SRTR data with data extracted from medical records by research coordinators from the nine-center A2ALL study. A2ALL data were collected independently of OPTN data submission (48 data elements among 785 liver transplant candidates/recipients; 12 data elements among 386 donors). At least 90% agreement occurred between OPTN/SRTR and A2ALL for 11/29 baseline recipient elements, 4/19 recipient transplant or follow-up elements and 6/12 donor elements. For the remaining recipient and donor elements, >10% of values were missing in OPTN/SRTR but present in A2ALL, confirming that missing data were largely avoidable. Other than variables required for allocation, the percentage missing varied widely by center. These findings support an expanded focus on data quality control by OPTN/SRTR for a broader variable set than those used for allocation. Center-specific monitoring of missing values could substantially improve the data.

Attitudes of the American public toward organ donation after uncontrolled (sudden) cardiac death.

Concerns about public support for organ donation after cardiac death have hindered expansion of this practice, particularly rapid organ recovery in the context of uncontrolled (sudden) cardiac death (uDCD). A nationally representative Internet-based panel was provided scenarios describing donation in the context of brain death, controlled cardiac death and uncontrolled cardiac death. Participants were randomized to receive questions about trust in the medical system before or after the rapid organ recovery scenario. Among 1631 panelists, 1049 (64%) completed the survey. Participants expressed slightly more willingness to donate in the context of controlled and uncontrolled cardiac death than after brain death (70% and 69% vs. 66%, respectively, p < 0.01). Eighty percent of subjects (95% CI 77-84%) would support having a rapid organ recovery program in their community, though 83% would require family consent or a signed donor card prior to invasive procedures for organ preservation. The idea of uDCD slightly decreased trust in the medical system from 59% expressing trust to 51% (p = 0.02), but did not increase belief that a signed donor card would interfere with medical care (28% vs. 32%, p = 0.37). These findings provide support for the careful expansion of uDCD, albeit with formal consent prior to organ preservation.

Efficient utilization of the expanded criteria donor (ECD) deceased donor kidney pool: an analysis of the effect of labeling.

We investigated the effect of the expanded criteria donor (ECD) label on (i) recovery of kidneys and (ii) acceptance for transplantation given recovery. An ECD is age > or = 60, or age 50-59 with > or = 2 of 3 specified comorbidities. Using data from the Scientific Registry of Transplant Recipients from 1999 to 2005, we modeled recovery rates through linear regression and transplantation probabilities via logistic regression, focusing on organs from donors just-younger versus just-older than the ECD age thresholds. We split the sample at July 1, 2002 to determine how decisions changed at the approximate time of implementation of the ECD definition. Before July 2002, the number of recovered kidneys with 0-1 comorbidities dropped at age 60, but transplantation probabilities given recovery did not. After July 2002, the number of recovered kidneys with 0-1 comorbidities rose at age 60, but transplantation probabilities contingent on recovery declined. No similar trends were observed at donor age 50 among donors with > or = 2 comorbidities. Overall, implementation of the ECD definition coincided with a reversal of an apparent reluctance to recover kidneys from donors over age 59, but increased selectiveness on the part of surgeons/centers with respect to these kidneys.

Improving organ procurement travel practices in the United States: proceedings from the Michigan Donor Travel Forum.

There are significant risks and inefficiencies associated with organ procurement travel. In an effort to identify, quantify, and define opportunities to mitigate these risks and inefficiencies, 25 experts from the transplantation, transportation and insurance fields were convened. The forum concluded that: on procurement travel practices are inadequate, there is wide variation in the quality of aero-medical transportation, current travel practices for organ procurement are inefficient and there is a lack of standards for organ procurement travel liability coverage. The forum concluded that the transplant community should require that air-craft vendors adhere to industry quality standards compatible with the degree of risk in their mission profiles. Within this context, a purchasing collaborative within the transplant community may offer opportunities for improved service and safety with lower costs. In addition, changes in travel practices should be considered with broader sharing of procurement duties across centers. Finally, best practice standards should be instituted for life insurance for transplant personnel and liability insurance for providers. Overall, the aims of these proposals are to raise procurement travel standards and in doing so, to improve the transplantation as a whole.

Race and ethnicity in access to and outcomes of liver transplantation: a critical literature review.

Racial/ethnic disparities in access to and outcomes of liver transplantation are an important topic given the increasing diversity in the United States. Most reports on this topic predate the advent of allocation based on the model for end-stage liver disease (MELD). For many patients with a variety of lethal conditions, liver transplantation is the only effective therapy, signifying the importance of equitable access to care. Racial/ethnic disparities have been described at various steps of the liver transplant process, including liver disease prevalence and treatment, access to a transplant center and its waitlist, receipt of a liver transplant and posttransplant outcomes. The purpose of this minireview is to critically evaluate the published literature on racial/ethnicity-based disparities in liver disease prevalence and treatment, transplant center referral, transplant rates and posttransplant outcomes. We identify the shortcomings of previous reports and detail the barriers to completing properly constructed analyses, particularly emphasizing deficits in requisite data and the need for improved study design. Understanding the nature of race/ethnicity-based disparities in liver transplantation is necessary to improve research initiatives, policy design and serves the broader responsibility of providing the highest quality care to all patients with liver disease.