Sirolimus Monotherapy Versus Sirolimus in Combination with Steroids and/or MMF for Immunosuppression After Liver Transplantation

Abstract

Calcineurin inhibitor (CI)-associated renal dysfunction has emerged as a major cause of morbidity and mortality after liver transplantation. In this retrospective study, we compared the efficacy, safety, and renal protective effect of sirolimus monotherapy (Group A; n = 26) with sirolimus in combination (Group B; n = 34) with steroids and/or mycophenolate mofetil (MMF) in liver transplant recipients who were switched from CI. Patients were switched abruptly or over a period of 2-4 weeks and followed for 17 +/- 10 months. Preconversion renal biopsies in five of six patients showed histological features consistent with CI nephrotoxicity. Serum creatinine increased in the year prior to conversion from 1.7 +/- 0.4 to 2.1 +/- 0.7 mg/dl (P = 0.009) and improved thereafter (1 month, 1.7 +/- 0.6, P < 0.001; 6 months, 1.6 +/- 0.5, P < 0.001; last follow-up, 1.7 +/- 0.9, P = 0.02); only four patients showed a significant decline in renal function after conversion. Seven (11.3%) patients experienced acute rejection (Group A, two; Group B, five; P = NS) and this resulted in the discontinuation of sirolimus in one patient. Fifty-four adverse events occurred in 40 (67%) patients, with similar numbers of adverse events in Group A and Group B. Most episodes of rejection (5/7; 71%), adverse events (45/54; 83%), and discontinuations (5/8; 63%) occurred within 6 months of conversion. We conclude that both sirolimus monotherapy and sirolimus in combination with prednisone and/or MMF are efficacious and safe in liver transplant recipients. Conversion to sirolimus was associated with an immediate improvement in renal function that was sustained during the follow-up.

Immunosuppression in liver transplant recipients with renal impairment

“…Overall, CNI interruption after mTOR inhibitor introduction was associated with a 6.5% incidence of rejection. Several small, uncontrolled, single-center reports have suggested renal sparing effects in patients with CNI-induced nephrotoxicity converted to either Sirolimus alone, or Sirolimus in conjunction with a low-dose CNI regimen [61,[73][74][75][76][77][78][79]. Yet, recent, usually controlled studies suggest that the advantage of Sirolimus-based immunosuppression on long-term renal function may be overstated [26,[61][62][63][64][65][66].…”

Late Acute Liver Allograft Rejection; A Study of Its Natural History and Graft Survival in the Current Era

“…The incidence of LAR remains variable (7Y23%) in the era of newer immunosuppressant agents such as tacrolimus, mycophenolate, and sirolimus (6,18,19). Despite these newer therapies, the sequelae such as ductopenic rejection continue to remain a clinical challenge.…”

Sirolimus Conversion in Liver Transplant Recipients With Calcineurin Inhibitor-Induced Complications: Efficacy and Safety

“…However, more and more studies proved that sirolimus monotherapy was safe and did not increase the risk of acute rejection. 5,9 In this study, only 4 in 25 patients (16.0%) developed acute rejection. Among them, 2 patients received readdition of calcineurin inhibitors, and intravenous steroid bolus therapy was initiated in the other 2 patients.…”

“…Sirolimus can limit or even avoid the adverse effects of calcineurin inhibitors and simultaneously guarantee adequate immunosuppression. [3][4][5][6] There are 2 regimens for converting to sirolimus from calcineurin inhibitors in liver transplant. 5 One is partial conversion by combining low-dose sirolimus with reduced calcineurin inhibitors, which was used in most studies of the early trials.…”

“…[3][4][5][6] There are 2 regimens for converting to sirolimus from calcineurin inhibitors in liver transplant. 5 One is partial conversion by combining low-dose sirolimus with reduced calcineurin inhibitors, which was used in most studies of the early trials. The other is complete conversion by cessation of calcineurin inhibitors and addition of sirolimus monotherapy or in combination with steroids and/or MMF.…”