Immunosuppression in Liver Transplantation: State of the Art and Future Perspectives.Curr Pharm Des. 2020 Jun 10 [Online ahead of print]CP
Novel drugs and combinations for immunosuppression (IS) after liver transplantation is one main reason of improved graft and patient survival seen in the last decades. The backbone of IS are still steroids and calcineurin inhibitors, although novel drugs are being introduced such as mammalian target of rapamycin inhibitors (mTOR inibitor). The challenge today along with increased patient survival is the adverse effects of long-term use of immunosuppressive drugs, mainly nephrotoxicity and other serious adverse effects. Concepts: The ultimate0 outcome after liver transplantation would be achieving tolerance, a state where all IS can be withdrawn. In the meantime, different approaches to reduce and withdraw IS have been tested out in different clinical trials with the aim to reduce the adverse effects of steroids and calcineurin inhibitors. This has formed the basis of today's clinical practice. The different combinations of immunosuppressive drugs have included mTOR inhibitor such as everolimus, and different induction drugs such as anti-interleukin 2 receptor antibodies. Regarding induction drugs, lymphocyte depleting (alemtuzumab and ATG) and non-depleting agents, such as basiliximab have shown advantageous effects.
Alongside steroid and calcineurin inhibitors reduction or elimination, current strategies for post-liver transplantation immunosuppression explore combinations of novel agents. The gauge (or yardstick) here is the fine balance between adverse effects of IS drugs and risk of rejection. Long-term maintenance IS regimens, development of tolerance and antibody-mediated rejection are also discussed in this review.