Organ Allocation: The European Models

Liver Transplantation in Europe

The number of liver transplants performed in Europe has increased, reaching a plateau of close to 6000 liver transplants performed annually ( Fig. 6-1 ). The number of listed patients waiting for a liver transplant continues to increase, and the gap is widening between them and the number of available liver grafts. Table 6-1 lists the liver transplant activity and organ donation rates in different European countries and regions. It is obvious from Table 6-1 that the liver transplantation activity and organ donation rates vary in the different countries and regions in Europe. Table 6-2 lists the main indications for end-stage liver disease and liver transplantation. As in the United States, liver cirrhosis resulting from chronic hepatitis C and alcoholic cirrhosis are the main and increasing indications for liver transplantation.

This chapter gives an overview and description of some different European organ allocation systems and organizations. The differences presented reflect differences in legislation, organ donation rates, indications for liver transplantation, and traditions in the practice of medicine in different countries and regions of Europe.

Organ Allocation

There are no uniform rules or systems for organ allocation in Europe or within the European Union. There are different organ exchange organizations for different countries and geographical areas, including the following:

• Organizacion Nacional de Transplantes (ONT) in Spain

• NHS Blood & Transplant (NHSBT) for the United Kingdom and Ireland

• Eurotransplant (Germany, the Netherlands, Belgium, Luxembourg, Austria, Hungary, Slovenia, and Croatia)

• Scandiatransplant (Sweden, Norway, Finland, Denmark, and Iceland)

• North Italian Transplant (NIT)

• Etablissement français des Greffes (EfG) in France

The majority of livers are allocated and transplanted within each procurement and exchange organization, but there is collaboration in case of surplus organs among these organizations.

Most organizations have similar rules with an urgent priority group that includes acute hepatic failure and early retransplantation following vascular thrombosis, as well as primary nonfunction. There are, however, important differences as well.

Although no universally accepted liver allocation rules exist, two methods are primarily followed. Organ allocation can be patient directed, as is the case in the United States and some European countries, or center directed, which is the case in other European countries (Spain, Scandiatransplant, and UKT). An organ allocation system is a matter of consensus among transplant teams, organizational structures, health authorities, and customer and patient organizations. Regardless of the model chosen, all systems work with two factor categories. The first category includes medical criteria such as blood group, human leukocyte antigen (HLA) compatibility (kidney transplantation), primary disease, donor and recipient matching, donor virological status, severity of recipient status, and others. The second category is nonmedical criteria, which include geographical distance and resources consumed. Waiting time or cold ischemia time may appear in either category.

The Committee of Ministers of the Council of Europe, considering that organ transplantation is severely restricted by availability of organs for transplantation, recognizes the need to set up a public system with an officially recognized network of transplant centers and an official register of patients on waiting lists. The committee also recommends that such a system provide complete information for health care professionals and the general public. This information should include criteria for registration and allocation, figures and flows of registered patients, and average waiting times for different groups of patients. The system must ensure, as far as possible, that no group of patients waits longer than another group.

Currently, few livers are exchanged between the different organizations. There is, however, an increasing collaboration with some former eastern European countries with recognized allocation systems and organizations. The goal is to use donor organs fully and, more importantly, to develop the field of organ transplantation in these countries to the level of the rest of Europe.

Spain

Liver transplant activity started in Spain in 1984 and reached 19,339 interventions on December 31, 2011, with a mean activity of more than 1000 transplants performed yearly. There are 25 transplant teams (1 per 1.88 million inhabitants), and 2 of them are pediatric. This liver transplant activity represents 6% of all the interventions performed in the world, while the Spanish population represents only 0.7% of world population. It is also the largest relative activity, reaching 23 to 25 liver transplants per million population (pmp). This achievement is a consequence of the strong effort made by all the professionals involved in donation and transplantation activities working within a public health service that provides health care for 99% of the population. The analysis of the long-term results of liver transplants is performed using data from the Spanish Liver Transplant Registry, jointly managed by the ONT and the Spanish Society of Liver Transplantation. As shown in other international registries, patient and graft survival have been improving across time.

Every hospital needs official authorization to perform liver transplants, and this implies the obligation to officially record all patients registered on the waiting list. The ONT provides essential support for organ procurement, allocation support, and management of the waiting list at a national level. Spain has the highest organ donation rate in the world, thanks to the outstanding donor detection and organ procurement organization, which is often referred to as the Spanish model for organ donation . Deceased donor organ donation rates have exceeded 30 donors pmp every year since 1998, reaching in 2011 the rate of 35.3 donors pmp. However, after analyzing the marked regional variability, with some autonomous communities registering more than 40 donors pmp in recent years, we believe there is still room for improvement. Thus ONT has created a large-scale, comprehensive strategy to achieve a substantial improvement in donation and transplantation in Spain in recent years.

Liver allocation in Spain is center oriented, because all available organs are referred to the national coordinating office for the rest of Spain. The allocation rules are decided by consensus among professionals from every transplant center and ratified by the representatives from regional health authorities. These rules are updated annually after analyzing in detail the liver transplant activity and taking into account several aspects: donor and recipient characteristics, waiting list time, mortality on the waiting list, probability of being transplanted for different groups of patients, and emergency and retransplantation rates per hospital.

Currently, national priority is given to liver emergencies, and it is clearly stated at a national level what is considered an emergency and the circumstances under which a patient can be listed as an urgent patient. In the absence of urgent patients, the organ is allocated successively to the hospital, city, region, or area, trying to reduce ischemia time. Two autonomous communities (Catalonia and Andalusia) have established a priority system at a regional level, which implies managing a single waiting list in the whole region. The final score for each patient takes into account the Model for End-Stage Liver Disease (MELD) score with several modifications according to different variables such as indication, combined transplants, pediatric recipients, possibility of split, and time on waiting list.

Finally, once an organ is offered to the transplant center, the final decision about the donor-recipient matching is made internally by the transplant team. To facilitate this decision, consensus guidelines have been recently developed with the support of the Spanish Society of Liver Transplantation. If no adequate recipient is available in Spain, the liver is offered to the rest of the European countries, although it is extremely unusual: we registered only one case in 2009 and no cases in 2010 and 2011.

An emergency liver transplantation in Spain is considered in two situations: (1) a patient having acute liver failure in the absence of any previous liver disease (a medical report must be sent to the national coordination office stating that the disease has developed in the last 8 weeks in a previous healthy liver) or (2) retransplantation within the first 7 postoperative days (in pediatric recipients, a period of 30 days is accepted). This emergency category implies national priority with the possibility of donor selection for the transplant unit. In case of simultaneous urgent situations, livers are allocated first to pediatric recipients (under 16 years of age) and next to the rest of the patients according to the time they have been included on the waiting list. Every year, liver transplant professionals analyze emergency rates according to the category and the center to design changes if necessary.

A review of the outcomes of all patients admitted to the liver transplant waiting lists in Spain from 2007 through 2011 ( Table 6-3 ) shows that a total of 10,729 patients were registered during that period. Of these, 466 (4.3%) were urgent patients. In the same period, Spanish units performed 5427 liver transplants; 379 of them (7%) were considered as national priority. Between 1.8 and 2.4 urgent liver patients pmp were registered every year. Among them, an average of 60% (54% to 65%, depending on the year) were fulminant liver failures, whereas primary graft failure within the first 7 days after surgery accounted for only 2% to 3% of all the transplants performed yearly in Spain. Analysis of the outcomes for these urgent patients shows that 81% of them were transplanted (80% of transplants were performed in the first 48 hours), with a mortality rate on the waiting list of around 7%.

As Figure 6-2 shows, patient clearance from the liver transplant waiting list in Spain did not change significantly from 2007 to 2011, after excluding urgent cases from the analysis (because of their specific priority), with a median time on the waiting list that ranged from 103 to 124 days, with approximately 1800 analyzed each year.

If we analyze patient clearance from the waiting list in Spain according to patient status, taking into account data from 2011 ( Fig. 6-3 ), 568 cases were still on waiting lists at the end of the period (December 31), 113 had died, and 1015 had received a liver transplant. The median waiting time for the grafted patients was 121 days; the median waiting time for the deceased patients was 84 days (intercentile range [ICR], 28.5 to 204), which was less than the median time of 151.5 days (ICR, 52 to 261.7) for those still waiting. These data indicate that patients are undergoing transplantation following medical criteria, with the sickest patients undergoing transplantation first. No significant differences were observed in clearance rates from the waiting lists in relation to age, weight groups, primary liver disease, and other studied variables.

As regards to other modalities of liver transplants, the living donor liver transplants and split-liver procedures performed during the reviewed period accounted for 6% of the activity: of the 5427 registered liver transplants, 130 were living donor livers (2.4%), 69 were split livers (1.3%), 55 were domino livers (1%), and 77 were from non–heart-beating donors (1.4%). Because we are convinced that some of these rates can be considered opportunities for improvement, we have designed specific collaborative projects to increase the donor pool with the objective of giving greater opportunities to patients on the waiting list.

United Kingdom Transplant

The first liver transplant in the United Kingdom (UK) was in 1968 at Addenbrookes, Cambridge, by Sir Roy Calne ; however, the first UK liver program started in 1983. The number of deceased organ donors in the UK fell over a number of years. An effort to reverse this trend was made by setting up an Organ Donation Taskforce, whose recommendations were implemented and followed by an increase in the number of donation after brain death (DBD) donors of 7% over the last 4 years. The number of donation after cardiac death (DCD donors has rapidly increased by 118% since 2007, in an effort to bridge the gap between the number of donors and the number of patients waiting for a transplant. Moreover, the number of people on the Organ Donor Register rose to 18.7 million, and deceased organ donation rose to 34.4%, reaching an unprecedented total of 1088 donors in 2011. Of these, 652 were DBD and 436 were DCD.

Approximately 700 liver transplants are performed yearly in the UK ( Fig. 6-4 ). Last year the number reached 791, registering an increase of 12% compared to the previous year. There are seven transplant units in the UK, six in England and one in Scotland. Three of these also have a pediatric liver transplant program. As of March 2012 there were 534 patients registered on the active waiting list for liver transplantation, a 9% increase compared to the previous year. Currently, on average, adult patients wait 142 days for a liver transplant, whereas pediatric patients wait an average of 78 days. A study looking into postregistration outcomes of 891 new elective liver registrations in the year 2008-2009 showed that at 1 year post registration 13% of patients either had died or had been removed from the list for deteriorating clinical condition ( Fig. 6-5 ).

The key players in regulating organ donation and transplantation in the UK are NHS Blood and Transplant (NHSBT) and the Human Tissue Authority (HTA).

NHSBT, a special health authority of the National Health Service (NHS), was established on October 1, 2005, to take over the responsibilities of two separate NHS agencies: UK Transplant (now renamed Organ Donation and Transplantation), founded in 1972, and the National Blood Service. Among its responsibilities is to provide a reliable, efficient supply of organs for transplantation. The advisory groups, which include representation from all designated transplant units, propose and monitor policies for organ donation, allocation, retrieval, and transplantation and recommend changes to the nationally agreed protocols for allocating organs. More specifically, the Liver Advisory Group and its subgroup Liver Selection and Allocation Working Party discuss matters regarding liver graft allocation, ensuring equity of access to transplantation.

The HTA is an independent watchdog that protects public confidence by licensing and inspecting organizations that store and use tissue for transplantation and other purposes. They also give approval for organ donations from living people through an independent assessment process. The HTA provides advice and guidance about two laws: the Human Tissue Act and the Quality and Safety Regulations. More recently the HTA was named as the competent organization for the European Union (EU) Organ Donation Directive, a European requirement that aims to bring all EU countries up to the same high quality and safety standards, and took the lead in developing a regulatory framework and implementation into legislation. These laws ensure human tissue is used safely and ethically, with proper consent.

NHSBT provides essential support for organ procurement via the new National Organ Retrieval Service introduced in the UK on April 1, 2010. The service comprises seven abdominal organ retrieval teams and six cardiothoracic organ retrieval teams. These teams are based in liver and cardiothoracic transplant centers, respectively. Each team has a designated area for which they are first on call, based on the premise that the travel time to any hospital in their area should be less than 3 hours. If a team is already retrieving when they are called to attend a donor, then a second team will be called in to retrieve. The system is led by consultant surgeons and is designed to improve efficiency and reduce travel time and costs.

Liver allocation in the UK is center oriented. All potential liver donors in the UK or Republic of Ireland must be reported by telephone to the NHSBT Duty Office. Donor zones are allocated to each center based on the number of new registrations on the waiting list of prospective candidates. This is to match the number of potential donors to the needs of the specific center, reflected by the scale of their waiting list. Should the local center decide not to use that liver, it is further offered to the other centers in accordance with the liver center rotation on the basis of a full offer to the first center and a provisional offer to the second in line. If the organ is declined, it will be fully offered to the second in line through the liver allocation sequence. The rotation system is determined according to each center’s transplant activity, based on a rolling 4 week period. The center with the least number of transplants during this period will appear at the top of the sequence, down to the center with the most number of transplants.

The allocation priority at each center is decided by transplant surgeons and physicians on call. National guidelines currently do not specify which patient to select when a liver suitable for more than one recipient is offered. There is a significant number of factors influencing the decision of the transplant professional, including quality and size of the donated liver, blood group, health condition of the potential recipient, and logistics of pressure on intensive care unit beds and on staff. The decision whether a liver should be transplanted into an individual should take account of both recipient and donor factors. In fact where possible the donor should be matched to the recipient who is expected to obtain the greatest transplant benefit from the procedure.