Perioperative and postoperative use of immunosuppressive agents in liver transplantation

Initial immunosuppression regimens were extrapolated from experiences found in renal transplantation and focused on a heavy induction regimen to prevent early acute rejection. In contrast to renal transplantations, acute rejection in liver transplantations may not be as deleterious as previously expected, and may actually allow for a better long-term graft survival. With more experience and on the basis of controlled clinical trials, the drug regimen after liver transplantation has undergone modification over the years despite the lack of a consensus on the "ideal regimens". In the late 1990s, centers started using more daclizumab and basiliximab, and less of the antilymphocyte preparations. In maintenance therapy regimens, the trend is to use MMF over azathioprine. Many centers withdraw steroids during the first postoperative year (as early as 3 months) and maintain only a minority of highly selected patients (patients with immunologically mediated diseases who experience rejection or recurrence) on long-term steroids. The choice between cyclosporine and tacrolimus is still debated, but there has been a general trend to using tacrolimus over cyclosporine. Steroid-sparing regimens are currently being tested in controlled clinical trials, and in patients with renal impairment, a sirolimus-based regimen is increasingly used. There is now a greater than 90% 1-year and a 70% to 80% 5-year survival rate for liver transplant recipients at most transplant centers. With the development of numerous and often very potent drugs, individualized orchestration and the challenge to choose the "best" combination of immunosuppressants has become even more important. As patient and graft survival has improved, attention has been shifted to reducing long-term complications of the immunosuppressive regimen. Future drugs should be compared and selected for their side-effect profile rather than for their potency.