The immunosuppressive pipeline: meeting unmet needs in liver transplantation.

Liver transplantation is now recognized as the treatment of choice for end-stage liver failure. Its success can be attributed largely to the generation of selective immunosuppressive agents, which have resulted in a dramatic reduction in the incidence of acute rejection and improvements in the short- and long-term outcomes of patients. However, the unresolved limitation of current immunosuppressive agents is long-term toxicity, which results in increases in the incidence and severity of cardiovascular, neurological, and renal diseases. Our recent understanding of the pathways of cell activation has resulted in the development of a new generation of immunosuppressive agents that may address the challenges facing transplantation today and allow the minimization or substitution of existing agents. Furthermore, advances in our understanding of the mechanisms of tolerance and the identification of biomarker signatures hold the promise that in some patients transplantation may be able to be performed without the need for long-term immunosuppression (tolerance).