Extrait

Background and study aims Following liver transplantation patients need to be given powerful drugs (known as immunosuppressive medication), to prevent organ rejection. These drugs are usually given for the rest of the patients life, which can result in important side effects. This the main reason why in the long run transplanted patients die more frequently than non-transplanted healthy individuals. Not all liver transplant patients, however, require lifelong immunosuppressive medication. Some of them develop a phenomenon known as operational tolerance and can discontinue this medication without rejecting the transplanted liver. In tolerant patients the withdrawal of anti-rejection medication could increase their survival and improve their quality of life. However, until now there have been no tests to identify tolerant patients before immunosuppression medication is stopped. Our research group recently identified a genetic test of tolerance in liver biopsies that can predict the outcome of immunosuppressive drug withdrawal. This test could radically change the long-term care of liver transplant patients. Who can participate? Liver transplant patients that received their new liver more than 3 years ago or more than six years ago if aged 18-49 or at least 50 years old respectively. What does the study involve? Participants first have a liver biopsy for the genetic test of tolerance. They are then randomly allocated to one of two groups. Patients randomized to group 1 are offered drug withdrawal regardless of the result of the genetic test. Patients randomized to group 2 undergo drug withdrawal if the genetic test is positive, and continue the immunosuppressive medication if the test is negative. By comparing the outcome of the 2 groups we will determine how much the test can benefit transplanted patients. What are the possible benefits and risks of participating? Chronic immuno-suppression (IS) is associated with a variety of life threatening side effects following liver transplantation, including infection, malignancy, hypertension, diabetes, nephrotoxicity and cardiovascular diseases. Calcineurin inhibitor induced nephrotoxicity, in particular, is responsible for a significant rate of chronic renal failure, need for renal replacement therapy and increased mortality. Elimination of calcineurin inhibitors may preserve waning renal function and avoid the associated morbidity and mortality risk.Identification of a reproducible and reliable tolerance signature will allow tailoring of IS to individual patient characteristics. It may also identify critical pathways responsible for the tolerant state that can be therapeutically exploited to induce tolerance in those who do not achieve it spontaneously. While there is abundant information in the literature suggesting that in carefully selected liver recipients IS withdrawal is feasible and safe, the procedure is not without risk, as it can induce immunologically-mediated allograft rejection. In this regard, the main risks of IS withdrawal are acute and/or chronic rejection, silent development of allograft fibrosis, potential complications associated with the need to increase IS to treat rejection episodes; and graft loss or patient mortality. Where is the study run from? King's College London (UK) When is the study starting and how long is it expected to run for? August 2015 to October 2017 Who is funding the study? National Institute for Health Research (UK) Who is the main contact? Ms Jurate Wall

Critère d'inclusion

• Topic: Hepatology; Subtopic: Hepatology; Disease: All Hepatology

Liens

• ictrp
• isrctn