Intraportal administration of low-dose recombinant human hepatocyte growthfactor enhances effects of hepatocellular transplantation

Background/Aims: Although recombinant human hepatocyte growth factor (rhHGF ) is a potent mitogen, the dose used for patients is still not clear and mu st be low to avoid untoward effects. Firstly, the optimal strategy of the d ose and route of rhHGF was investigated. Secondly, low-dose rhHGF, which wo uld induce proliferation of transplanted hepatocytes, was explored using Na gase analbuminemic rats. Methodology: 1) Concentrations of rhHGF in the portal vein were measured af ter continuous administration of titrated rhHGF through the jugular vein or portal vein. 2) F344 rat hepatocytes (2 x 10(7) cells) were transplanted i n the liver of Nagase analbuminemic rats. On the 7th day, the rats were sub jected to a low-dose rhHGF treatment. Results: When the rats were given rhHGF in a dose of 50 mug/kg/day, the mea n concentration in the portal vein (0.8 +/- 0.1ng/mL) was almost similar to the minimum concentration which stimulated hepatocyte proliferation in vit ro. When low-dose rhHGF (50 mug/kg/day) was administered directly into the portal vein following hepatocyte transplantation in Nagase analbuminemic ra ts, the serum levels of albumin were significantly higher than in other gro ups. It was found that the concentration of rhHGF in the portal vein were 3 .1 +/- 0.5 ng/mL with continuous intraportal infustion and 0.8 +/- 0.1 ng/m L with continuous systemic infusion. Conclusions: It was found that the minimal dose of rhHGF needed to stimulat e hepatocyte proliferation was 50 mug/kg/day. With rhHGF (50 mug/kg/day), c ontinuous intraportal infusion afforded a more favorable outcome in case of proliferation of hepatocytes.