Hepatocyte growth factor prevents chronic allograft dysfunction in liver-transplanted rats.

BACKGROUND: Hepatocyte growth factor (HGF) is a growth factor with multiple biologic properties, including mitogenic, morphogenic, anti-apoptotic, and antifibrogenic activities. Long-term administration of the deletion variant of HGF (dHGF) might contribute to the prevention of chronic liver allograft dysfunction, which is attributed to immunologic and nonimmunologic reactions. METHODS: Low-dose tacrolimus was administered to rat-liver recipients after transplantation. Effects of dHGF on transplanted livers treated with low-dose tacrolimus were investigated. RESULTS: Rats receiving liver transplants treated with only low-dose tacrolimus administration showed chronic allograft dysfunction. Treatment with dHGF prolonged the survival time of rats that received liver allografts and suppressed fibrosis of liver allograft. Treatment with dHGF also suppressed the expression levels of interleukin (IL)-1beta, caspase-1, and transforming growth factor (TGF)-beta mRNAs in liver allografts. CONCLUSIONS: The findings indicate that dHGF may prevent chronic liver-allograft dysfunction and thus may become a novel treatment for chronic liver-allograft dysfunction.