Causes of liver steatosis influence the severity of ischemia reperfusion injury and survival after liver transplantation in rats.

Liver steatosis is a leading cause of graft disposal in liver transplantation; however, the degree of steatosis has been so far the almost single factor determining whether the grafts is acceptable or not. We investigated how the cause of liver steatosis affects graft function in rat orthotopic liver transplantation (OLT). OLT was performed using two types of steatotic liver grafts; the fasting and hyper alimentation (FHA) and methionine and choline deficient diet (MCDD) models. The FHA and 4-week MCDD feeding (MCDD4wk) groups showed similar liver triglyceride levels without signs of steatohepatitis; therefore, the two groups were compared in the following experiment. With 6-hour cold storage, 7-days survival rate after OLT was far worse in the FHA than the MCDD4wk group (0% vs. 100%, P = 0.002). With 1-hour cold storage, the FHA group showed higher aspartate and alanine aminotransferase levels and histological injury score in zone 1 and 2 at 24 hours after reperfusion than the Normal liver and MCDD4wk groups. Intrahepatic microcirculation and tissue ATP level were significantly lower in the FHA group after reperfusion. Hepatocyte necrosis, sinusoidal endothelial cell injury and abnormal swelling of mitochondria were also found in the FHA group after reperfusion. Tissue malondialdehyde levels were higher in the MCDD4wk group before and after reperfusion; however, the grafts upregulated several antioxidant enzymes soon after reperfusion. Conclusion: Even though the degree of steatosis was equivalent, the two liver steatosis models possessed quite unique basal characteristics and showed completely different response against ischemia reperfusion injury and survival after transplantation. Our results demonstrated that the degree of fat accumulation is not a single determinant for the fate of steatotic liver graft.