Efficacy, Tolerance, and Safety of Mammalian Target of Rapamycin Inhibitors as Rescue Immunosuppressants in Liver Transplantation

Conversion to everolimus in maintenance liver transplant patients: A multicenter, retrospective analysis

“…Previous reports have described no rejection episodes after the introduction of everolimus, [19][20][21] but in 2 trials in which CNI therapy and adjuvant immunosuppressants were withdrawn relatively aggressively, the rates of rejection were 7% 18 and 10%. 17 In the current study, in which there were no protocol-specified withdrawals of other agents, there was a very low rate of acute rejection (<2.0%).…”

“…Single-arm studies have demonstrated that maintenance liver transplant patients can be converted from CNIs to everolimus safely at later time points with a low rate of acute rejection. [17][18][19][20][21][22] Like kidney transplant recipients, 23 liver transplant recipients with kidney dysfunction apparently need to be switched from CNI immunosuppression to everolimus either early after transplantation 16 or before the establishment of severe dysfunction. 17 In clinical practice, some centers now initiate everolimus in maintenance liver transplant patients who develop kidney dysfunction or, less frequently, posttransplant neoplasms and attempt to withdraw CNI therapy.…”

mTORC1 promotes aging-related venous thrombosis in mice via elevation of platelet volume and activation

“…45 In contrast, other studies demonstrated that rapalog use was safe and not associated with an increased risk of arterial or VTE. 27,28,32 Mural thrombi are formed by circulating platelets interacting with activated endothelial cells or the subendothelial matrix. The specific roles of platelets or endothelial cell mTORC1 in thrombosis have not been elucidated.…”

“…Studies on patients receiving rapalogs after liver or kidney transplantation have reported inhibitory, stimulatory, or no effects of rapamycin on arterial thrombosis. [27][28][29][30][31][32] Individual variations, treatment periods, and targeting of multiple cells within the vascular system, including monocytes, endothelial cells, neutrophils, and platelets, by rapamycin may contribute to these conflicting results. The specific roles of platelet mTORC1 in age-related VTE and underlying mechanisms have not yet been established.…”

Treatment of recurrent hepatocellular carcinoma after liver transplantation

“…Although there is a good deal of literature concerning the preemptive use of sirolimus in patients undergoing transplantation for HCC, sirolimus as a treatment for HCC recurrence is reported in only 1 significant series. 21 This study documented the safety of the drug, but no outcomes for the 7 patients with recurrent HCC were described. It is unclear whether sirolimus should be added to calcineurin inhibitors or should replace them in this setting.…”