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This combination refers to the standard-of-care maintenance immunosuppressive regimen evaluated in the LIFT (Liver Immunosuppression Free Trial) conducted by King's College London. The regimen includes calcineurin inhibitors (tacrolimus and cyclosporine) and antimetabolites (mycophenolate mofetil, mycophenolic acid, and azathioprine). These small molecule agents work through distinct mechanisms to prevent allograft rejection: tacrolimus and cyclosporine bind to immunophilins (FKBP12 and cyclophilin A, respectively) to inhibit calcineurin, thereby blocking T-cell activation and IL-2 production. Mycophenolate and azathioprine interfere with purine synthesis and lymphocyte proliferation. The LIFT trial specifically investigated the safety and feasibility of biomarker-guided withdrawal of these medications in stable liver transplant recipients to achieve operational tolerance, though the study was terminated early due to the poor diagnostic performance of the transcriptional biomarker test.
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