Stimulation of liver regeneration and function after partial hepatectomy in cirrhotic rats by continuous infusion of recombinant human hepatocyte growth factor

Abstract Background/Aims: Radical resection is accepted as one of the most curative treatments for hepatocellular carcinoma. However, most patients have coexisting cirrhosis and their liver function is usually impaired. It is therefore important to stimulate the regeneration and function of the remnant cirrhotic liver after hepatectomy. Hepatocyte growth factor is a potent mitogen that has been suggested to play a crucial role in liver regeneration. Methods: In this study, we performed 45% hepatectomy in rats with cirrhosis induced by thioacetamide, and administered recombinant human hepatocyte growth factor (rhHGF) with dextran sulfate by continuous infusion into the jugular vein with an infusion pump. Results: rhHGF stimulated an increase in the wet weight of the remnant liver compared with untreated control rats. The proliferating cell nuclear antigen labeling index showed that this increase resulted from the stimulation of DNA synthesis. Serum levels of liver enzymes increased after hepatectomy, but returned to the prehepatectomy level more rapidly in rhHGF-treated rats than in controls. rhHGF increased hepatic protein synthesis above prehepatectomy levels and also markedly increased the serum levels of hepatic lipid metabolites. Conclusions: These results demonstrate that continuous intravenous infusion of rhHGF enhances the growth and function of the remnant liver in rats with cirrhosis after partial hepatectomy. Therefore, rhHGF may be useful after hepatic resection in patients with cirrhosis.