HEPATOCYTE GROWTH FACTOR IMPROVES SURVIVAL OF STEATOTIC LIVER TRANSPLANTATION IN RATS

Abstract

P71 Background/Aims; Transplantation of liver with severe steatosis may result in primary nonfunction (PNF) of the graft. As described previously, human recombinant hepatocyte growth factor (hrHGF) protected fatty grafts against cold preservation injury in rats. In the present study, we examined the effects of hrHGF on survival and graft function in rat fatty liver transplantation model. Methods; Severe steatosis was induced by a 15-day choline-deficient diet in male Lewis rats. The fatty graft was orthotopically transplanted in normal male Lewis rat after 12 hr cold preservation in UW solution. In the HGF group, donor rats were pretreated with a single bolus of systemic injection of hrHGF (10μg/rat), and 30μg of hrHGF was also added to the perfusion/preservation solution. Animal survival, graft function and morphological changes were compared with those of the untreated group. Liver cell apoptosis was detected by TUNEL stain and liver regeneration was evaluated by BrdU stain at 2 hrs after reperfusion of the liver graft. Results; One week survival was significantly improved in the HGF group compared with the untreated group (83% vs. 33%, p<0.01, n=18/group). AST, ALT and LDH levels in the rinse effluent at the end of cold preservation and serum ALT and LDH at 2 hrs after reperfusion were significantly lower in the HGF group. Although there was no significant difference in hyaluronic acid (HA) level in the rinse effluent at the end of preservation between the two groups, exogenous HA uptake rate (HAUR) at 2 hrs after reperfusion was improved in the HGF group (0.62±0.05 vs. 0.79±0.11, p<0.05). hrHGF pretreatment also significantly reduced the sinusoidal endothelial cell (SEC) apoptotic index (1.65±0.60% vs. 4.90±1.25%, p<0.01) and increased BrdU incorporation index (2.07±0.62% vs. 0.06±0.04%, p<0.01) at 2 hrs after reperfusion. More severe sinusoidal SEC damage was observed by transmission electron microscope in the untreated group than that in HGF group. Conclusions; hrHGF prevented the death of PNF in steatotic liver transplantation by attenuating preservation–reperfusion injury and facilitating recovery of the graft, probably through its antiapoptotic properties and acceleration of liver regeneration at early stage after transplantation.