Declined Liver Grafts – Analysis of the German Donor Population from 2010 to 2018
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"Declined Liver Grafts – Analysis of the German Donor Population from 2010 to 2018" was published in the Zeitschrift für Gastroenterologie.
The lack of suitable allografts limits the availability of liver transplantation in Germany. The quality of potentially available German donor livers has to date not been analyzed.
Analysis of all donors for potential liver transplantations reported to the Eurotransplant by the German Organ Transplantation Foundation from 2010 to 2018. Categorization of transplanted and discarded organs utilizing available histopathological reports and predefined extended criteria for organ donation.
A total of 8594 livers were offered for transplantation, of which 15.2 % were discarded. During the analysis period the proportion of donor livers from extended criteria donors increased from 65 % to 70 % (p = 0.005). In 2018, 21.3 % of offered donor livers were discarded, more than half (56.4 %) of these organs came from donors meeting multiple extended criteria. Livers were significantly more likely to be not transplanted, when from donors of older age (> 65 years; 41 vs. 28 %), BMI > 30 kg/m2 (29 vs. 14 %) or elevated transaminase levels (all p < 0.001).
Despite the consistent organ scarcity in Germany, a relevant amount of livers cannot be transplanted due to a multitude of organ quality limitations. This should stimulate the search for concepts such as normothermic ex vivo machine perfusion to evaluate, protect and potentially improve organ quality.

Authors are Simon Moosburner, Nathanael Raschzok, Christina Schleicher, Detlef Bösebeck, Joseph M.G.V. Gaßner, Paul V. Ritschl, Axel Rahmel, Igor M. Sauer, and Johann Pratschke.
Z Gastroenterol. 2020 Aug 24. doi: 10.1055/a-1199-7432. Online ahead of print.
EKFS grant | Metabolic reconditioning of steatotic rat liver grafts by normothermic ex vivo machine perfusion
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The Else Kröner Fresenius Stiftung will fund the project "Metabolic reconditioning of steatotic rat liver grafts by normothermic ex vivo machine perfusion" (PI: Priv.-Doz. Dr. Nathanael Raschzok) for two years.

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.
DFG Research Grant
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Priv.-Doz. Dr. Nathanael Raschzok receives a research grant from the Deutsche Forschungsgemeinschaft (DFG) for his project "Defatting of steatotic liver grafts by normothermic ex vivo machine perfusion with DNP" in collaboration with Prof. Dr. med. Andreas Birkenfeld, Universitätsklinikum Carl Gustav Carus, Dresden.

Transplantation of steatotic marginal liver grafts is associated with a certain risk of graft dysfunction, primary non-function, and biliary complications, which results in a worse outcome compared to transplantation of unimpaired livers.
We hypothesize, that normothermic machine perfusion combined with adequate pharmacological intervention can prevent the deleterious effect of ischemia-reperfusion injury on macrovesicular grafts by a) minimizing the negative effect of cold storage, and by b) actively decreasing the intracellular fat content of the graft.
Mild mitochondrial uncoupling by DNP decreases the intrahepatic fat content of steatotic liver grafts during normothermic ex vivo machine perfusion. Efficient defatting can be safely achieved ex vivo with DNP concentrations that would be toxic in vivo. Systemic side effects of DNP are prevented by exclusive hepatic exposure through machine perfusion, and by washing DNP out of the liver graft at the end of the perfusion period. The synergetic effects of normothermic perfusion and defatting with DNP will prevent ischemia-reperfusion injury and make severely steatotic liver grafts acceptable for transplantation.
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