The incidence of viral hepatitis is increasing and hepatitis C is now a major and growing cause of chronic liver damage leading to cirrhosis. Viral hepatitis is now responsible for one third of all cases of liver cirrhosis. Our laboratory has been examining the role of the immune system in autoimmune and viral cirrhosis. We have made considerable progress in our understanding of these processes and have found that the liver damage in hepatitis C infection is due to the immune system rather than to the virus itself. We are also studying molecular mechanisms of tissue repair and regeneration as well as defining molecular-cellular interaction with the liver using a transgenic model of liver injury.
Liver transplantation is the only effective therapy for end stage liver failure.
Approximately four out of every five transplanted livers are still functioning after one year. In spite of this success, chronic rejection of the transplanted organ and complications of long term immunosuppression result in unacceptable morbidity and mortality. One means to avoid this problem is to induce immunological tolerance to the transplanted liver. We have been studying an animal model in which a transplanted liver is accepted without requirement for immunosuppression. Our findings show that liver acceptance is associated with very rapid and marked immune activation in the recipients, while rejection is associated with a more gradual, but eventually much greater immune response in the transplanted organ itself.