Gene therapy for liver cirrhosis

Abstract

Liver cirrhosis is the irreversible end result of chronic liver disease and is characterized by fibrous scarring and hepatocellular regeneration. It is a major cause of morbidity and mortality worldwide and is induced by factors such as chronic hepatitis virus infection, drug abuse and alcohol abuse. The ideal strategy for the treatment of liver cirrhosis should include prevention of fibrogenesis, stimulation of hepatocyte mitosis and reorganization of the liver architecture. Hepatocyte growth factor (HGF) gene therapy has been investigated in a rat model of liver cirrhosis. In rats with lethal liver cirrhosis produced by dimethylnitrosamine, repeated transfection of the HGF gene into skeletal muscle induced a high plasma level of HGF and tyrosine phosphorylation of the c-Met/HGF receptor. Hepatocyte growth factor gene transduction inhibited fibrogenesis and hepatocyte apoptosis and also produced resolution of fibrosis in the cirrhotic liver. Hepatocyte growth factor gene therapy may have the potential to be useful for the treatment of patients with liver cirrhosis.