Maintenance immunosuppression for adults undergoing liver transplantation: a network meta-analysis

Abstract

Based on low-quality evidence from a single small trial from direct comparison, tacrolimus plus sirolimus increases mortality and graft loss at maximal follow-up compared with tacrolimus. Based on very low-quality evidence from network meta-analysis, we found no evidence of difference between different immunosuppressive regimens. We found very low-quality evidence from network meta-analysis and low-quality evidence from direct comparison that cyclosporine A causes more retransplantation compared with tacrolimus. Future randomised clinical trials should be adequately powered; performed in people who are generally seen in the clinic rather than in highly selected participants; employ blinding; avoid postrandomisation dropouts or planned cross-overs; and use clinically important outcomes such as mortality, graft loss, renal impairment, chronic kidney disease, and retransplantation. Such trials should use tacrolimus as one of the control groups. Moreover, such trials ought to be designed in such a way as to ensure low risk of bias and low risks of random errors.

Sixteen-Year Cohort of Liver Transplantation in the National Health System in Brazil: Analysis of Immunosuppression Maintenance Therapies

“…Analyzing Kaplan-Meier’s curves, it is possible to observe a higher graft survival rate on patients under tacrolimus-based therapeutic regimens when compared to those based on cyclosporine in the Full cohort. This finding is similar to that one of another cohort ( Jonas et al, 2005 ) and the finding of Rodriguez’s meta-analysis ( Rodríguez-Perálvarez et al, 2017 ). In multivariate analysis in the Full cohort, a higher proportion of azathioprine or mycophenolate use was related to a worse prognosis for the graft.…”

“…When these immunosuppressants are compared over longer periods, evidence shows no difference in patients’ survival. However, it is known that cyclosporine presents a higher rate of graft loss than tacrolimus ( Rodríguez-Perálvarez et al, 2017 ).…”

Activation of mTOR Signaling Pathway in Hepatocellular Carcinoma

“…Sirolimus (or rapamycin) entered the market first but the initial phase II randomized trial in liver transplantation had to be prematurely stopped because the experimental arm consisting of sirolimus plus tacrolimus resulted in an increased risk of graft loss and sepsis [107]. A subsequent network meta-analysis of randomized trials have demonstrated that sirolimus-based immunosuppression is associated with increased mortality rates as compared with other protocols and therefore there are concerns about using sirolimus as a first-line therapy in patients receiving a liver transplantation [108]. Everolimus has an improved safety profile as compared with sirolimus.…”

Traditional Chinese Medicine for Refractory Nephrotic Syndrome: Strategies and Promising Treatments

“…Of calcineurin inhibitors, tacrolimus is preferred over cyclosporine for treating many types of autoimmune diseases and for preventing graft rejection after organ transplantation. This is largely owing to the fact that tacrolimus has consistently demonstrated better therapeutic effects and fewer adverse effects than cyclosporin in most comparative studies [ 58 – 62 ]. However, narrow therapeutic index and unpredictable bioavailability in humans (5%–67% with average of 27%) have made tacrolimus administration challenging for clinical practice [ 63 ].…”