Modulating activity of the necroptosis pathway to rescue steatotic liver grafts – DELFAT

Liver transplantation is the only therapeutic option for patients with end-stage liver disease. However, the rising prevalence of chronic liver diseases, such as non-alcoholic fatty liver disease (NAFLD), has increased the number of patients requiring liver transplantation, and the duration on waiting lists. The presence of steatosis in more than 30% of hepatocytes is a major cause of immediate liver graft dysfunction. Among 400 liver grafts discarded each year in France, 25% are not used because of steatosis, representing 10% of liver transplantations. The use of fatty liver grafts for transplantation would significantly increase the pool of donors and therefore, has become a topic of great interest. In this project, we will use ex situ normothermic organ perfusion to rescue fatty liver grafts by depleting them in fat and protecting them from ischemic injury during perfusion. We will target the necroptosis signaling pathway implicated both in fat storage and ischemia.