Morphologic alteration of hepatocytes and sinusoidal endothelial cells in rat fatty liver during cold preservation and the protective effect of hepatocyte growth factor

Background Fatty liver grafts are considered to be one of the main factors of primary nonfunctioning graft in transplantation. We investigated here, t he hepatic damage during cold preservation in a rat fatty liver model by ul trastructural observation, and examined the effect of human recombinant hep atocyte growth factor (hrHGF) on amelioration of the cold-preserved graft c ondition. Methods. Wister rats were fed a choline-deficient diet (CDD) for 7 days. Li vers were stored in cold University of Wisconsin (UW) solution for 0, 4, an d 24 hr, We evaluated the ultrastructural alteration of the hepatocytes, si nusoidal architecture, and endothelial cells (SECs) by scanning and transmi ssion electron microscopy, Ex vivo, we measured alanine aminotransferase (A LT) in first effluent as an index of hepatocyte injury and the hyaluronic u ptake rate (HUR) as that of SEC damage. We injected hrHGF into rats fed CDD for 7 days through the portal vein and also added it to the UW solution to determine whether or not the agent ameliorated the hepatic damage in cold- preserved fatty livers. Results. In rats fed CDD for 7 days, the lesion occupied by fat deposits ap peared to enlarge with the duration of cold preservation leading to the dis arrangement of sinusoidal architecture, Furthermore, sinusoidal endothelial damage, in which gaps, blebs, microvilli, and sinusoid denudation were det ected, appeared to be more severe in these livers than in the corresponding control livers. ALT significantly increased in the 4-hr cold-preserved liv ers of rats fed CDD for 7 days, HUR decreased with 4-hr cold preservation a nd/or with CDD feeding. Administration of hrHGF prevented the expansion of fatty droplets and reduced SEC injury as detected by morphological ob serva tions. Increase of ALT in first effluent was inhibited to about one fourth the level observed in the 4-hr cold-preserved livers of rats fed CDD. Moreo ver, HUR significantly increased with the pretreatment of hrHGF. Conclusion. The hepatic injury in both hepatocytes and SECs in cold-preserv ed fatty liver graft developed more rapidly and severely than in the corres ponding controls and demonstrated a protective effect of hrHGF.