Background: Liver transplantation from DCD donors is associated to ischemia/reperfusion (IR) lesions, which may increase the risk of post-transplant hepatocellular carcinoma (HCC) recurrence. Normothermic graft perfusion (including extracorporeal membrane oxygenation –ECMO) can prevent IR lesions and potentially cancer recurrence. These issues were assessed in rat orthotopic liver transplantation (OLT) models.

Methods: Syngeneic Fisher OLTs were performed, with the intraportal injection of 2*106 HCC cells (JM-1) at the end of the procedure. Donors from the control group (n=8) were heart-beating, those from the DCD group (n=8) underwent ten-minute inflow liver clamping prior to retrieval, and those from the ECMO group (n=8) underwent two-hour liver reperfusion after the ten-minute liver clamping. IR lesions were assessed by histology and according to LFTs. HCC growth was quantified by MRI (week one to two). Serum and liver cytokine profiles were assessed 12h after transplantation.

Results: The presence of IR lesions was confirmed in the DCD group, with the presence of endothelial lesions and hepatocyte necrosis, and increased AST and ALT levels (p=0.007 and p=0.05). These lesions were reversed by the two-hour reperfusion in the ECMO group. HCC growth was three times higher in the DCD group (p=0.02 vs. control), but was prevented in the ECMO group (p=0.56 vs. control).

These observations were related to a stronger pro-inflammatory cytokine profile in the DCD group (vs. control and ECMO).

Discussion: IR lesions associated to liver transplantation from DCD donors lead to an increased risk of post-transplant HCC recurrence and growth. This observation can be reversed by normothermic graft perfusion prior to retrieval.

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