Evolution of immunosuppression in liver transplantation: contribution of cyclosporine

Liver transplantation has become the standard therapy for patients with end-stage liver disease or acute liver failure, with excellent outcomes in terms of quality of life and length of survival. The use of immunosuppressive agents, without any doubt, has played a crucial role in the establishment of this technique and improved short- and long-term survival rates. Eventually, mortality from acute or chronic rejection may be entirely eliminated. Minimizing the adverse effects of immunosuppressive agents is essential to improve long-term survival and quality of life. In this chapter, we review the history of immunosuppressive agents for liver transplantation with consideration of the pre- and the postcyclosporine eras. We also review the development and contributions of cyclosporine, the excellent outcomes from C2 monitoring, comparisons between the cyclosporine microemulsion and the oil-based formula, as well as between cyclosporine microemulsion versus tacrolimus. In addition, details are provided on the newer immunosuppressive agents: mycophenolate mofetil, sirolimus, and the IL-2 receptor antagonists, as well as agents in development: CAMPATH 1-H, thymoglobulin, everolimus, FT720, and FK778.