Apoptosis in liver transplantation: A mechanism contributing to immune modulation, preservation injury, neoplasia, and viral disease

Although clinical liver transplantation has become a reality for the treatment of previously fatal end-stage chronic liver disease of fulminant hepatic failure, there are several limitations to its use. Allograft rejection is prevented only by induction of an artificial state of immunocompetence in the recipient by the use of nonspecific immunosuppression. This increases the risk of infection and malignancy. These complicating can be avoided only if tolerance to specific donor organ antigens is achieved and nonspecific immunosuppression is avoided. Understanding the role of apoptosis in the immune response to transplantation and study of the molecular and biochemical modulation of apoptosis may provide fertile ground for investigation relevant at liver transplantation. Such study may yield novel approaches to (1) the diagnosis, treatment, or prevention of rejection after transplantation; (2) therapeutic modulation of apoptosis in effector and target cells to limit immune-mediated damage; (3) rational immunosuppressive drug design; (4) strategies to allow development of graft tolerance, e.g., by selective deletion of antigen-specific T-cell populations; and (5) further avenues for research into the pathophysiology of conditions associated with transplantation such as malignancy, infection, preservation injury, and recurrent disease.