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P4. IMMUNOLOGY AND LIVER TRANSPLANT
Coordinator:
Dr. Miquel Navasa
Associate Coordinator:
Dr. Marina Berenguer
Despite the fact that Program 4 covers various topics, its primary area of research is liver transplant . About 15,000 liver transplants are performed worldwide every year today . Results are satisfactory in terms of transplant recipient survival rates . Survival is about 90% 1 year after the transplant, about 75% after 5 years, and 65% after 10 years . Nevertheless, liver transplant still presents a series of important clinical problems:
Immunosuppression: a) must be optimised to adapt to the needs of each patient in order to reduce the risk of rejection and toxicity; b) the possibility of completely withdrawing immunosuppression in patients showing graft tolerance, who may represent a considerable proportion of transplant patients several years after the transplant, c) suitably detecting and handling complications resulting from immunosuppressants, d) influence of immunosuppression in hepatocarcinoma recurrence, and e) non-invasive markers of rejection . For this reason, some of the objectives of this group focus on the identification and clinical validation of a panel of predictive biomarkers of the risk of rejection, clinical progression of the graft and personal response to immunosuppressant treatment . The implementation of these biomarkers in clinical practice would allow stratifying patients according to risk of rejection and improving the choice of immunosuppressant treatment as well as the identification of patients who are candidates for minimization without it entailing a risk of reactivation of the effector response of the immune system (risk of rejection in the maintenance phase) .
Recurrence of the pre-transplant disease, particularly hepatitis C, studies performed by the members of the programme have allowed defining progression of liver fibrosis in transplant patients . After the marketing of new and potent viral agents, the mechanisms of liver damage have lost their interest in these patients . However, the study of the reversibility of fibrosis and the associated mechanisms holds interest both in transplant patients (it would be important to treat before irreversible damage sets in) and in patients on a transplant wait list (if the damage is reversible, the transplant is not necessary) . Therefore, Programme 4 also deals with research for this issue .
Complications of the immunosuppressant treatment . Post-liver transplant diabetes mellitus is associated with worse results, a higher rate of infections, rejection and mortality having been reported . Other complications, such as the onset of neoplasias or the increase in cardiovascular risk, are important limiting factors of survival of liver transplant patients . This programme includes the study of these complications in their working projects .
Disproportion between the number of organ donors and the number of patients on a liver transplant wait list . Therefore, over the past few years, on one hand a series of actions that sought to palliate this problem by means of investigating strategies that allow increasing the number of liver grafts suitable for transplant were implemented, and on the other hand, improvements were made in managing the transplant wait list . These aspects are also grounds for research for Program 4 groups .
The research group has established new targets of therapeutic action based on the modulation of adipocytokines both in liver resections and liver transplant in marginal bodies, which can have a favourable effect on patients who are subjected to liver resections or liver transplant and in a reduction in liver transplant wait lists . The results obtained by the research group have further allowed participation in competitive programmes intended for translation experimental results to clinical practice, which will result in patent application and in the creation of a spin-off .
On the other hand, it is very important to point out the important collaboration established with important groups that are dedicated to studying liver diseases, particularly with the Viral Hepatitis Group (Dr . X . Forns) and with the Portal Hypertension Group (Dr . J . Bosch), as well as with international groups .
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