Treating liver cirrhosis in dogs with hepatocyte growth factor gene therapy via the hepatic artery

Abstract

Liver cirrhosis, an irreversible result of chronic liver disease, has had no effective therapy except liver transplantation. We previously reported successful therapy of liver cirrhosis in rats using the hepatocyte growth factor gene. We presently performed hepatocyte growth factor gene therapy in dogs with liver cirrhosis to examine the feasibility for clinical use. Liver cirrhosis was established in beagles by administrating dimethylnitrosamine. Naked human hepatocyte growth factor gene or naked LacZ gene was injected repeatedly into livers via the hepatic artery using a porter catheter in dogs with cirrhosis. Human hepatocyte growth factor gene expression was detected in livers by immunohistochemical staining and an enzyme-linked immunosorbent assay. Serum liver function test results improved with hepatocyte growth factor gene therapy, which also inhibited hepatic transforming growth factor-beta1expression and reversed fibrosis in cirrhotic liver, improving survival of the dogs. As naked hepatocyte growth factor gene therapy via the hepatic artery proved simple, safe, and effective in larger animals with cirrhosis, this therapy may be clinically applicable.