**2. Transplantation**

The success of liver transplantation has resulted in a progressively increasing demand for such treatment. However, as mentioned above, at the same time the availability of donor organs has diminished, resulting in the number of potential recipients for liver transplantation far exceeding organ supply. Given this, several strategies have been explored in the last decade or so with the aim to increase access to liver transplantation. These include obtaining organs from non-heart-beating donors and live donors, and splitting and using livers from expanded donor criteria. Also, the introduction of the Model for End-Stage Liver Disease (MELD) system implemented February 27 of 2002 in the United States helped Organ Procurement Organizations to prioritize patients waiting for a liver transplant. The MELD score is a numerical scale used for adult liver transplant candidates that ranges between 6 (less ill) and 40 (gravely ill). The individual score determines how urgently a patient needs a liver transplant within the next 3 months. The number is calculated using the most recent laboratory tests – table 1(6).


Table 1. Laboratory values used in the MELD score calculation

The MELD score is then distributed in 4 levels according with the severety of the disease. Less than or equal to 10, 11-18, 19-24 and greater than or equal to 25, being the last the level that includes the most severe patients. Nevertheless, MELD score is not the only factor used for organ allocation to a patient.

In general, for organ distribution a donor is matched to a potential recipient on the basis of several factors: ABO blood type, body size, degree of medical urgency and MELD score. Organ Procurement Organizations (e.g. OPTN/UNOS, etc) uses a computerized point system to distribute organs in a fair manner. Recipients are chosen primarily on the basis of medical urgency within each ABO blood group. Waiting time is only a factor when patients have the same MELD score.

Nevertheless, there are four Special Case Exceptions that will be assigned a higher MELD score than that assigned by the patient's laboratory test results:


In addition to the previously mentioned four special case exceptions, a transplant center can apply for a MELD exception for a patient whose medical urgency is not reflected by the MELD score(6).

The implementation of more fair and efficient allocation systems, improvement in the immunosupressive regimens, and the increase of living donation have all helped to increase overall patient survival and graft survival in the past decade in the United States. The number of livers transplanted also increased to a all time high in 2006, with a marked decrease on the waiting time for liver transplantation after MELD implementation, especially for the sickest patients.

An example of the impact of these improvements is the increase of 6% (86% in 2007) and 16% (87% in 2007) of the unadjusted 1-year graft survival for deceased donor and living donor liver recipients between 1998 and 2007, respectively. These accounts also for an improvement of 3% (89% in 2007) and 11% (91% in 2007) of the unadjusted 1-year patient survival for deceased donor and living donor liver recipients for the same period, respectively(7). However, these numbers decrease significantly for the 5-year patient survival. In 2007 it was 74% and 79% for deceased donor and living donor liver recipients, respectively. These numbers decrease even further for the 10-year patient survival, where in 2007 we had 61% and 71% patient survival for deceased donor and living donor liver recipients, respectively. One important note is that patient survival was higher than graft survival ~5%, because of the opportunity for repeat liver transplantation in the event of graft failure(8).

These numbers highlight the need for novel therapies that can increase patient survival, as well as lower costs to the health care systems. Tolerance research and its clinical induction is a good example of this. The identification of molecular signatures in tolerant patients in whom immunosuppression could be stopped, and induction of tolerance, through lymphocyte depletion or T lymphocyte co-stimulation blockade, are the most advanced approaches to reduce complications of immunosuppression(9).
