BACKGROUND: New strategies for immunosuppression (IS) after liver transplantation (LTx) are in part responsible for the increased patient and graft survival seen over time. With a few basic exceptions-notably the continued use of steroids and calcineurin inhibitors (CNIs)-IS drugs and regimens being used today are different from those used 30 years ago. While graft loss due to acute or chronic rejection has become rare, the side effect burden of IS drugs exerts a significant toll on patients. CONCEPTS/TRENDS: CNIs continue to form the backbone of IS regimens, although their use is hampered by nephrotoxicity and other adverse effects. Consequently, a variety of CNI reduction or withdrawal strategies have formed the basis of clinical trials or entered into clinical practice. These trials have included the use of everolimus, an mTOR inhibitor, and anti-interleukin-2 receptor antibodies. Basiliximab, as well as other lymphocyte nondepleting and depleting agents, have shown benefit in induction regimens. SUMMARY: Along with steroid reduction or elimination, current strategies for IS after LTx continue to explore novel combinations of agents, with an aim toward striking a balance between diminution of rejection and the need for avoiding adverse effects of the IS drugs. Long-term maintenance strategies are also discussed in this review, as is development of tolerance and antibody-mediated rejection.
BACKGROUND: New strategies for immunosuppression (IS) after liver transplantation (LTx) are in part responsible for the increased patient and graft survival seen over time. With a few basic exceptions-notably the continued use of steroids and calcineurin inhibitors (CNIs)-IS drugs and regimens being used today are different from those used 30 years ago. While graft loss due to acute or chronic rejection has become rare, the side effect burden of IS drugs exerts a significant toll on patients. CONCEPTS/TRENDS: CNIs continue to form the backbone of IS regimens, although their use is hampered by nephrotoxicity and other adverse effects. Consequently, a variety of CNI reduction or withdrawal strategies have formed the basis of clinical trials or entered into clinical practice. These trials have included the use of everolimus, an mTOR inhibitor, and anti-interleukin-2 receptor antibodies. Basiliximab, as well as other lymphocyte nondepleting and depleting agents, have shown benefit in induction regimens. SUMMARY: Along with steroid reduction or elimination, current strategies for IS after LTx continue to explore novel combinations of agents, with an aim toward striking a balance between diminution of rejection and the need for avoiding adverse effects of the IS drugs. Long-term maintenance strategies are also discussed in this review, as is development of tolerance and antibody-mediated rejection.
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