EKFS grant | Metabolic reconditioning of steatotic rat liver grafts by normothermic ex vivo machine perfusion
Liver transplantation is the treatment of choice for end-stage liver disease, yet the number of transplant candidates constantly exceeds the organ supply. The imbalance between demand and supply of liver grafts is dramatically exacerbated by the rising prevalence of obesity and the metabolic syndrome, which both show a strong correlation with steatosis hepatis. Liver grafts with macrovesicular steatosis above 30% are associated with delayed graft function and lower graft and patient survival, and livers with >60% steatosis are generally discarded from transplantation. Within the next 10 years, the overall liver graft utilization could potentially be halved due to the rising prevalence of steatosis, emphasizing the urgent clinical need to find solutions to make steatotic livers acceptable for transplantation.
In this project the hypothesis is tested whether metabolic reprogramming of steatotic liver grafts will 1) restore hepatocyte function, 2) activate lipid catabolism, 3) increase resistance to ischemia reperfusion damage, and 4) alleviate overwhelming inflammatory processes in the early phase of post-transplant regeneration with beneficial long-term impact for graft function and recipient survival.