Novel Therapeutic Modalities for Hepatic Diseases

Summary

Exciting novel therapeutic modalities to treat inherited and acquired hepatic diseases have been introduced and investigated during the last decade. The fundamental concepts as well as research data from animal studies and early clinical trials in hepatic gene therapy, hepatic drug targeting, hepatocellular transplantation, and the use of extracorporeal liver assist devices are reviewed. The delivery of transgenes to hepatocytes is achieved with different vector systems and gene transfer strategies. In vitro and in vivo results for monogenetic metabolic disorders, hepatocellular carcinoma, and viral hepatitis are promising. However, daunting problems remain before routine clinical application can be established. Chimeraplasty, a new gene repair strategy, is an interesting alternative to gene augmentation. Hepatic drug targeting is based on vehicles, especially liposomes, with a high affinity to liver cells, and liposome formulation and structure can be modulated to improve targeting ability. The potential of hepatocellular transplantation is to support or replace liver function in acute and chronic hepatic failure, and to assist hepatic function in patients with congenital enzyme deficiencies. Experience with porcine hepatocytes and human cell lines in extracorporeal liver support devices is encouraging, and already some patients have successfully been bridged to whole-organ transplantation. Further effort is needed to improve the novel treatment strategies. In particular, biosafety and efficacy must be stressed before large clinical trials are considered.