Multicentric outcome analysis of sirolimus-based immunosuppression in 252 liver transplant recipients

Abstract

Summary The use of sirolimus (SRL) in orthotopic liver transplantation (OLT) has been controversial after experimental data suggested an increased risk of hepatic artery thrombosis (HAT). To assess the safety and efficacy of SRL as de novo immunosuppression in OLT recipients. Outcomes of 252 OLT patients who received SRL were compared with outcomes of 291 OLT recipients who received calcineurin inhibitor in a retrospective study. Primary outcomes of this study were: patient‐ and graft survivals, vascular, biliary, wound complications and rejection rates. Secondary outcomes were: postoperative infection rate, bone marrow and renal function and changes of lipid levels. Patient‐ and graft survivals, rejection and infection rates were similar. In the SRL group, HAT occurred in 1.2%, biliary complications in 19.4%, and incisional hernias in 9.1%. In the control group the incidence of HAT was 5.8% (P = 0.004), biliary complications 18.5% (P = NS) and incisional hernias 7.2% (P = NS). Patients on SRL experienced significantly higher levels of serum triglycerides but fewer acute cellular rejections. Bone marrow and renal functions were similar in both the groups. Our findings would suggest that SRL is safe and effective for very selected OLT recipients. Randomized controlled trials are necessary to confirm our results.

De Novo Sirolimus and Reduced-Dose Tacrolimus Versus Standard-Dose Tacrolimus After Liver Transplantation: The 2000–2003 Phase II Prospective Randomized Trial

“…Published experience of de novo use of sirolimus subsequent to this trial has been limited to observational and retrospective studies, which have not shown an increased risk of graft failure or HAT (15,20,31). Rates of HAT seen in the sirolimus arm in this study (8%) were much higher than those in other single-and multicenter observational studies (approx.…”

“…Indeed, salient features that may differentiate the favorable experience of single centers using sirolimus versus those reported in the current study may be a lower total dose of immunosuppression and/or amelioration of factors that may be associated with a thrombotic tendency (e.g. elevated hematocrit or timing of administration) (12,18,31).…”

“…Rates of HAT seen in the sirolimus arm in this study (8%) were much higher than those in other single-and multicenter observational studies (approx. 1-3%) (12,15,31). Lower doses of sirolimus have been employed in some of the studies reporting lower or similar rates of HAT.…”

Review on immunosuppression in liver transplantation

“…The incidence of HAT related to sirolimus use varies in different reports. Molinari et al [78] reported a higher incidence of HAT in sirolimus group with CNI group but no HAT was reported in LT recipients on sirolimus in another study by Harper et al [79] . Similar results were reported by Fischer et al [80] , and they did notice no HAT following conversion of CNIs to everolimus.…”

583 Everolimus Immunosuppression Reduces Serum Expression of Fibrosis Markers in Liver Transplant Recipients

“…However, this drug has also been used off-label in liver and lung transplantation patients [24][25][26][27] . At our center, the use of everolimus in LT recipients is approved in situations such as renal dysfunction or adverse events like neurotoxicity due to CNI, development of de novo malignancies, recurrence of hepatocellular carcinoma, and the presence of predictors of a high risk of hepatocellular carcinoma recurrence in the explanted liver (satellitosis, vascular infiltration and multinodularity disease) [28,29] .…”