Sirolimus: A potent new immunosuppressant for liver transplantation

Background Sirolimus (rapamycin) is a new immunosuppressant that appears to be synergistic with cyclosporine in kidney transplantation, but with a dif ferent side-effect profile. This pilot study evaluated sirolimus in liver t ransplantation. Methods. Patients undergoing orthotopic liver transplantation for primary t umors (8), and later for nonmalignant disease (7), received one of three si rolimus-based immunosuppressive regimens. Protocol A comprised sirolimus, m icroemulsion cyclosporine (target whole blood concentration: 100 ng/ml), an d prednisolone; protocol B omitted prednisolone; and protocol C was sirolim us alone. By 3 months after transplantation, all patients were receiving si rolimus as monotherapy. Results. Fifteen patients were treated with a follow-up of 117-806 days. Re jection was more common on monotherapy than double therapy, and absent on t riple therapy. The drug was generally well tolerated, with only three patie nts discontinuing sirolimus: one for hyperlipidemia, one for pneumocystis p neumonia, and one for inability to tolerate the taste of the drug. Two pati ents discontinued cyclosporine early, both as a result of neurological comp lications; they continued on sirolimus monotherapy, Five patients died; one suffered a cardiac arrest, and four died from sepsis in association with g raft-versus-host disease, recurrent tumor, a paralyzed right hemidiaphragm, and primary nonfunction. Conclusions. Sirolimus combined with cyclosporine provided potent immunosup pression of liver allografts, and sirolimus monotherapy was adequate and we ll tolerated as maintenance therapy. Side effects of sirolimus over the sho rt period of follow-up were uncommon and reversible with dose reduction or cessation of therapy.