Tacrolimus de novo versus ciclosporin after liver transplantation: an updated meta-analysis and systematic review

Background For immunosuppression after liver transplantation (LT) most centers use tacrolimus as backbone, but some use ciclosporin.. There was one meta-analysis of randomized controlled trials (RCTs) de novo after LT comparing both with older formulations and high target blood levels, while another old meta-analysis compared more current drug formulations and regimens. However, several issues remained unresolved. This systematic review and meta-analysis aimed to update evidence from RCTs regarding ciclosporin versus tacrolimus in de novo adult LT recipients, and review current formulations and regimens. Methods A literature search was conducted for randomized controlled trials between 1998 and 2024, comparing ciclosporin and tacrolimus de novo in adult first deceased donor LT recipients. The relative risks at 12 months for mortality, graft loss, acute rejection, post-transplantation diabetes mellitus (PTDM) and hypertension were assessed. Results From 384 publications, 12 RCT’s were included. After 12 months, tacrolimus was superior to ciclosporin regarding rejection (RR 1.17, 95 % CI 1.02 – 1.36), mortality (RR 1.31, 95 % CI 1.05 – 1.63) and hypertension (RR 1.28, 95 % CI 1.10 – 1.49) but inferior regarding PTDM (RR 0.61, 95 % CI 0.49 – 0.75). There was no difference in graft loss after 12 months (RR of 1.29,95 % CI 0.67 – 2.47), but with significant heterogeneity. Reporting of renal function was insufficient for meta-analysis. In some studies drug levels were somewhat above those currently used. Conclusions In the first year after adult LT, tacrolimus is not only superior to ciclosporin regarding mortality and hypertension, but also in preventing rejection. Ciclosporin is superior regarding PTDM.