The MELD System for Liver Allocation

The recent implementation of the Model for End-stage Liver Disease (MELD)/Pediatric End-stage Liver Disease (PELD) system for the allocation of cadaveric liver organs in the US represents a dramatic change in organ allocation policy. Previous allocation algorithms used a categorical stratification system, in which candidates were ranked by the length of time waiting within these strata. This resulted in the ranking of patients by time waiting on the list, not by their need for a transplant. Moreover, these previous systems had not been validated for their accuracy in predicting the severity of liver disease and did not meet the needs of the enlarging population of appropriate candidates with end-stage liver disease. The MELD was identified as a potentially more accurate measure of liver disease, and a new plan for liver allocation incorporating the MELD score and virtually eliminating waiting time was devised. Several diagnoses for which liver transplantation is indicated were identified as not being served by the MELD system, so alternative mechanisms were developed for these cases. The new allocation system went into effect on February 27, 2002. One year after implementation, there was a statistically significant increase in the number of cadaveric transplants and a slight reduction in the number of waiting list deaths compared with the previous system in the year prior to MELD.As the system evolves and improvements are made, patients have a much more objective measure of the severity of their liver disease, which is comparable regardless of the geographic location or physician. This change to a mathematically-based system that defines the risk of death represents a change in the way patients and caregivers will think about the liver transplant list. In addition, payors now have a much more objective measure of the severity of illness and can more accurately risk-adjust their comparisons of centers and patients. The new system directs organs to sicker patients, and waiting candidates are likely to experience significant declines in their quality of life while waiting. In addition, because this new policy will result in more severely ill patients receiving transplants, the costs of care are likely to increase, although preliminary results suggest that survival rates have not changed. The change to this new, more evidence-based system is a significant paradigm shift in organ allocation policy. Patients, caregivers, and payors should also be prepared for continuous evolution of the system as more data become available.     

Benchmarking organ procurement organizations: a national study.

OBJECTIVE: An exploratory examination of the technical efficiency of organ procurement organizations (OPOs) relative to optimal patterns of production in the population of OPOs in the United States. DATA SOURCES: A composite data set with the OPO as the unit of analysis, constructed from a 1995 national survey of OPOs (n = 64), plus secondary data from the Association of Organ Procurement Organizations and the United Network for Organ Sharing. STUDY DESIGN: The study uses data envelopment analysis (DEA) to evaluate the technical efficiency of all OPOs. PRINCIPAL FINDINGS: Overall, six of the 22 larger OPOs (27 percent) are classified as inefficient, while 23 of the 42 smaller OPOs (55 percent) are classified as inefficient. Efficient OPOs recover significantly more kidneys and extrarenal organs; have higher operating expenses; and have more referrals, donors, extrarenal transplants, and kidney transplants. The quantities of hospital development personnel and other personnel, and formalization of hospital development activities in both small and large OPOs, do not significantly differ. CONCLUSIONS: Indications that larger OPOs are able to operate more efficiently relative to their peers suggest that smaller OPOs are more likely to benefit from technical assistance. More detailed information on the activities of OPO staff would help pinpoint activities that can increase OPO efficiency and referrals, and potentially improve outcomes for large numbers of patients awaiting transplants.     

Assessing emerging technologies--the case of organ replacement technologies: volume, durability, cost

OBJECTIVES: The aim of this study was to estimate thresholds for production volume, durability, and cost of care for the cost-effective adoption of liver organ replacement technologies (ORTs). METHODS: We constructed a discrete-event simulation model of the liver allocation system in the United States. The model was calibrated against UNOS data (1994-2000). Into this model, we introduced ORTs with varying durability (time to failure), cost of care, and production volume. Primary outputs of interest were time to 5 percent reduction in the waiting list and time to 5 percent increase in expected transplant volume. RESULTS: Model output for both calibration and validation phases closely matched published data: waiting list length (+/-2 percent), number of transplants (+/-2 percent), deaths while waiting (+/-5 percent), and time to transplant (+/-11 percent). Reducing the waiting list was dependent on both ORT durability and production volume. The longer the durability, the less production volume needed to reduce the waiting list and vice versa. However, below 250 ORT/year, durability needed to be >2 years for any significant change to be seen in the waiting list. For base-case costs, all ORT production volume and durability scenarios result in more transplants per year at less total cost of care/patient than the current system. ORTs remain cost saving until manufacturing costs are >5 times base-case costs, production is less 500 ORT/year, and durability <6 months. CONCLUSIONS: Although there remain many technical challenges to overcome, as long as ORTs can meet these threshold criteria, they have the potential of transforming the world of end-stage liver disease.     

Immunology in medical practice. XXX. Organ transplantation: indications and results

During the past 30 years, solid organ transplantation has developed into a routine medical procedure. Currently, one-year transplant survival rates for kidney, heart, liver and pancreas are between 80 and 90%; for most organs, the long-term results are fair with 5-year survival rates of 60%. Inclusion criteria for potential recipients have become less stringent. These days, potential recipients are rarely excluded on the basis of their calendar age alone. The development of more and stronger immunosuppressive drugs has facilitated transplantation across wider immunological differences between donor and recipient with good results. While the number of patients on the waiting lists for organ transplantation increased, the number of organs offered for donation decreased. This has resulted in waiting times of several years for most organ transplantations. While the short-term outcome has improved significantly over the past decades, the long-term outcome has not. Most renal transplants, for example, are lost due to chronic rejection. The challenge for the future will be to improve the long-term outcome of organ transplantation and to decrease the morbidity associated with chronic immunosuppressive therapy.     

Using a standardized donor ratio to assess the performance of organ procurement organizations

OBJECTIVE: To develop a Standardized Donor Ratio (SDR) as an outcome measure for evaluating the effectiveness of organ procurement organizations (OPOs). DATA SOURCES/STUDY SETTING: All deaths by cause in the United States during 1993-1994 as reported in the Vital Mortality Statistics, Multiple Cause of Death files. The OPO-specific data were provided by the United Network for Organ Sharing (UNOS). STUDY DESIGN: Each OPO's expected number of donors was calculated by applying national donation rates to deaths with potential for donation in 24 age, sex, and race cells. The SDR was calculated by dividing the observed number of donors by the expected number. The chi2 tests of the hypothesis that the OPO's performance differed from the national norm of 1.0 were performed. The SDR was compared to the existing performance standard based on the unadjusted number of donors per million live population in the OPO's service area. An ordinary least squares (OLS) regression assessed predictors of the SDR. PRINCIPAL FINDINGS: The SDRs ranged from 0.41 to 1.99. Twenty-nine of 64 OPOs had SDRs significantly different than 1.0. The SDRs were positively associated with the percent of white living population and the number of organ types transplanted per transplant center served by the OPO. CONCLUSIONS: The SDRs can be used by Centers for Medicare and Medicaid Services (CMS), UNOS, and OPOs to target quality improvement initiatives, present more accurate comparisons of OPO performance, and develop public policy on the evaluation of the effectiveness of organ procurement efforts.     

Transplantation-transmitted tuberculosis--Oklahoma and Texas, 2007

Approximately 28,000 organ transplants were performed in the United States in 2007. When infections are transmitted from donors, the implications can be serious for multiple recipients. Tuberculosis (TB), a known infectious disease complication associated with organ transplantation, occurs in an estimated 0.35%-6.5% of organ recipients in the United States and Europe posttransplantation. In 2007, the Oklahoma State Department of Health identified Mycobacterium tuberculosis in an organ donor 3 weeks after the donor's death. This report summarizes results of the subsequent investigation, which determined that disseminated TB occurred in two of three transplant recipients from this donor, and one recipient died. Genotypes of the donor and recipient TB isolates were identical, consistent with transmission of TB by organ transplantation. To reduce the risk for TB transmission associated with organ transplantation, organ recovery personnel should consider risk factors for TB when assessing all potential donors. In addition, clinicians should recognize that transplant recipients with TB might have unusual signs or symptoms. When transmission is suspected, investigation of potential donor-transmitted TB requires rapid communication among physicians, transplant centers, organ procurement organizations (OPOs), and public health authorities.     

Potential organ-donor supply and efficiency of organ procurement organizations

The authors estimated the supply of organ donors in the U.S. and also according to organ procurement organizations (OPOs). They estimated the number of donors in the U.S. to be 16,796. Estimates of the number of potential donors for each OPO were used to calculate the level of donor efficiency (actual donors as a percent of potential donors). Overall, donor efficiency for OPOs was 35 percent; the majority was between 30- and 40-percent efficient. Although there is room to improve donor efficiency in the U.S., even a substantial improvement will not meet the Nation's demand for organs.     

Utilisation of organs proceeding from donors with heart failure: review of the pathogenesis of organic damage and the possible mechanisms of prevention

There is an evident imbalance between the number of patients awaiting a kidney transplant and the availability of organs proceeding from donors with brain death. A high number of patients die each day from heart failure, whose organs could be used for transplants if specific care is employed. Although centres do exist where these methods of extraction are established, the problems of organic damage have yet to be resolved, since one third of the organs are still lost, besides the increase in the need for early dialysis, and the number of dysfunctioning grafts two years after the transplant, when this type or organ is employed. There is increasingly detailed knowledge of the pathogenesis of organic damage following heart failure and reanimation, as well as of the damage following the conservation and reimplantation of the kidney. Knowledge of the maximum time of hot ischemic that an organ can withstand is of crucial importance if organs are not to be unduly discarded. Besides, the increasing understanding of the physiopathology of oxidative stress could make it possible for us, through the use of antioxidants, to attempt to improve the utilisation of the organs and diminish the incidence of dysfunctions and rejections.     

Prospective study of the quality of life in patients assessed for liver transplantation: outcome in transplanted and not transplanted groups.

The quality of life in adult patients with chronic liver disease who were considered for transplantation was assessed prospectively over a 2 year period, for both those who did and did not subsequently receive transplants. The main outcome measures were the Nottingham Health Profile and survival. Of the 109 patients who completed an entry profile, 27 were transplanted, 71 not transplanted during the study period, and 11 rejected for transplant. Quality of life and severity of liver disease at entry was worse for the transplant group, whose survival at 15 months from entry was 81% compared with 78% for those not transplanted. Among transplant survivors there were marked improvements in quality of life, whilst amongst those not receiving transplants there was little change. In conclusion, liver transplantation was effective in improving quality of life in patients with chronic liver disease, but comparison between transplant and non-transplant patients is difficult because of differences between the groups.     

The Scottish Liver Transplant Unit: current and future perspectives

The Scottish Liver Transplant Unit (SLTU) opened in 1992 and has now performed over 900 liver transplants. During this time there have been major changes in both organ donation and transplantation. Currently liver transplantation is restricted by limited organ supply. Scotland has one of the lowest rates of organ donation in Europe and one of the most rapidly increasing rates of cirrhosis. The consequent waiting list mortality has driven innovations including increasing use of marginal grafts, organs donated after cardiac death, split-liver transplants and the development of living-donor liver transplantation. To maintain liver transplantation, there is an urgent need to increase organ donation rates and to find novel treatments which optimize outcomes from marginal grafts. This review addresses the surgical aspects of liver transplantation and how these have evolved over the two past decades. Major changes are currently underway in organ donation organization, and there is continuing refinement of organ treatment and storage. A number of measures to maintain and improve organ preservation and function are currently being evaluated in clinical trials, and cell therapy holds significant potential for the future. Scotland has a rising need for liver transplantation and the SLTU continues to provide high-quality care and to be at the forefront of the latest advances in organ transplantation.     

Some ethical aspects of donation and transplantation

Ethical and legal consensus in our country bases the practice of donations and transplants on different ethical principles, which are contained in the legislation, closely conforming to the four principles of principialist bioethics: autonomy, beneficence, non-maleficence, and justice. The level of donations achieved in our milieu might, in fact, be related to a strict respect for these principles by the health professionals, as well as to the excellent organisation of the transplant world. Many scientific, technical and ethical challenges have had to be met to reach the present state of the transplant. And there are many current challenges. The article only analyses some of these due to their technical, ethical and social repercussions: organ transplants involving a live donor, the public request for organs, the organ market, the transplant of non-vital organs (basically the face transplant), the use of stem cells and the banks of umbilical cord cells. The aim of the article is to state the ethical problems raised by these new practices, in order to lay the foundations for a moral deliberation that must necessarily involve the whole of society.     

Eurotransplant--new possibility for the Hungarian transplantation

The year 2010 was a milestone in the history of transplantation in Hungary. The State Secretary for Health Issues announced a program in order to solve the serious problems of organ transplantation: 1) to increase waiting lists, 2) to raise donor numbers, 3) to establish a lung transplant program in the country, 4) to promote education and increase the knowledge base regarding transplantation for the public and the medical profession, and finally, 5) to begin negotiations for Hungary to join Eurotransplant. Joining Eurotransplant has been a priority of the transplant community. Finally, this year saw the Budapest Transplant Center perform 20% of their kidney transplants from living donors, up from a 5% frequency historically, an operation which is available in all four centers from this year.     

The declaration of Istanbul in the Philippines: success with foreigners but a continuing challenge for local transplant tourism

The Philippine government officially responded to the Declaration of Istanbul on Organ Trafficking and the related WHO Guidelines on organ transplantation by prohibiting all transplants to foreigners using Filipino organs. However, local tourists have escaped the regulatory radar, leaving a very wide gap in efforts against human trafficking and transplant tourism. Authorities need to deal with the situation seriously, at a minimum, by issuing clear procedures for verifying declarations of kinship or emotional bonds between donors and recipients. Foreigners who come to the country for transplants with same-nationality donors constitute a problem that is replicated in many transplant centers around the world. Also, emotionally related living donors continue to pose challenges for ethics committees, especially because of the realities associated with the existence of extended families. Those who find themselves facing these issues need to be armed with clear protocols for going through the process of verifying documents and individual declarations assiduously. There is also a need for international referral mechanisms at least to ensure that governments are aware when their citizens travel for transplant so they can take steps they consider suitable to address the vulnerabilities of exploited persons.     

A study on organ transplantation waiting lines in Brazil's Unified National Health System

This study analyzes the waiting lines for solid organ transplants in Brazil's Unified National Health System. By using a queuing theory model, we estimate the waiting times for different organs under alternative scenarios. The model reveals the elasticity of various waiting times with respect to arrival and service rates for organ transplantation within the system. Average waiting time for a solid organ transplant is very long and highly elastic in Brazil. The article discusses some important possibilities for reducing such waiting times.     

Pandemic influenza A H1N1 vaccine in recipients of solid organ transplants: immunogenicity and tolerability outcomes after vero cell derived, non-adjuvanted, whole-virion vaccination

During the 2009/10 pandemic of influenza A (H1N1), the American Society of Transplantation and other health organizations recommended that immunocompromised patients should be vaccinated as the key preventive measure. Since there are no data available for the immunogenicity of the unadjuvanted pandemic influenza vaccine in immunocompromised patients - as opposed to the adjuvanted preparation - the objective of this study was to evaluate the immunogenicity of an adjuvant-free H1N1 vaccine in recipients of solid organ transplants. Patients were recruited at the Vienna General Hospital, Austria. The vaccination schedule consisted of 2 doses of a whole-virion, vero cell derived, inactivated, non-adjuvanted influenza A/California/07/2009 (H1N1) vaccine given with an interval of 3 weeks. A hemagglutination inhibition (HI) assay on blood samples obtained prior to the first and after each vaccination was used for serologic analysis. The primary immunologic endpoint was the seroconversion rate, defined as the proportion of subjects with an individual 4-fold increase in HI titer of at least 1:40. In addition, virus-specific IgG antibodies to the pandemic H1N1 strain were measured using a commercially available ELISA.Twenty-five organ transplant patients (16 males, 9 females) aged 25-79 years were vaccinated and provided blood samples for serologic analysis. The time elapsed since transplantation was 10 months to 25 years (mean: 9 years; 95% CI 6-13 years). The vaccine was well tolerated and no local adverse events were noticed. After two vaccinations 37% of the patients demonstrated seroconversion in the HI assay as defined above and 70% had virus-specific IgG antibodies. Among the HI vaccine responders were 6 of 14 heart transplant recipients and 1 of 4 liver transplant recipients. The number and type of immunosuppressive agents did not significantly differ in their effect on the immune response.Our results show that the novel vero cell derived and adjuvant-free pandemic A/California/07/2009 (H1N1) influenza vaccine induced limited but measurable immune responses in adult recipients of solid organ transplants.     

Transplant rejections? Tighter organ-transplant restrictions from the CMS could lead to fewer programs; some are leery of changes based on outcomes

At least 10 organ transplant centers are expected to lose their Medicare-approved status next year under new regulations meant to tighten standards and increase survival rates, according to Barry Straube, the CMS' chief medical officer. The updated rules worry providers, who say that the number of transplants doesn't accurately indicate quality, but neither does it automatically point to waste or fraud.     

Age and the Allocation of Organs for Transplantation: A Case Study

What role should age play in the allocation of organs for transplantation? Historically, older patients have not been listed as candidates for transplantation on the assumption that greater benefit could be obtained by favoring younger candidates, raising questions of equity and age discrimination. At the same time, organs offered for donation by the very old are frequently rejected because of concerns about length of viability. We examine a local case that challenges these practices: the liver from an elderly donor was successfully transplanted into an older patient. After exploring some of the potential problems with such a solution, we propose creating a second pool of organs from the very old for transplantation into older candidates, thus expanding the number of organs available, saving additional lives, and including the elderly more visibly in our transplant system.     

Characteristics of Rural and Urban Cadaveric Organ Transplant Donors and Recipients

CONTEXT: Health disparities have been found when comparing rural and urban populations. Purpose: To compare characteristics of rural and urban cadaveric transplant donors and recipients. METHODS: We used deidentified individual-level data on 55,929 cadaveric transplant donor-recipient exchanges between 2000 and 2003 and examined the relative rates of donating and receiving cadaveric transplants for rural compared to urban residents, as defined by ZIP Codes. FINDINGS: When compared to their urban counterparts, rural organ donors were more likely to have died from head trauma, drowning, motor vehicle accidents, or suicide and less likely to have died from cerebrovascular events, cardiac events, or homicide (P < .001 for all). Rural transplant recipients had lower levels of educational attainment and were less likely to have had the transplant financed by private insurance (P < .001 for all). While we found no statistical difference in days wait to organ transplantation, rural residents were more likely to donate than to receive cadaveric organs (P < .001). CONCLUSIONS: The differences in organ donation that we found warrant further exploration.     

Discriminators of willingness to consider cadaveric kidney donation among black Americans.

Black Americans were classified as either willing or unwilling to consider serving as kidney donors according to a combination of demographic and social psychological variables. Findings indicated that, in addition to selected religious variables, willingness to consider donation was associated with gender, age, source of information about organ donation, perceived need for transplants among blacks, self-acceptance of transplant organs and perception of bias in the selection of transplant recipients. Implications of the findings for social work practice and future research are discussed.     

Iniquities in the access to renal transplant for patients with end-stage chronic renal disease in Brazil

The objective of this present study is to analyze individual and contextual factors associated with access to renal transplant in Brazil. An observational, prospective and non-concurrent study was carried out, based on data from the National Database on renal replacement therapies in Brazil. Patients undergoing dialysis between 01/Jan/2000 and 31/Dec/2000 were included and monitored up to the point of transplant, death or until the end of the study period. Variables that were analyzed included: individual variables (age, sex, region of residence, primary renal disease, hospitalizations); and context variables concerning both the dialysis unit (level of complexity, juridical nature, hemodialysis machines and location) and the city (geographic region, location and HDI). Proportional hazard models were adjusted with hierarchical entry to identify factors associated with the risk of transplant. The results point to differentials in access according to socio-demographic, clinical, geographic and social factors, indicating that the organ allocation system has not eliminated avoidable disparities for those who compete for an organ in the nationwide waiting list.