The optimal immunosuppression management to prevent early rejection after liver transplantation: A systematic review of the literature and expert panel recommendations

Background The optimal immunosuppression protocol to prevent early acute cellular rejection (ACR) after liver transplantation (LT) avoiding prolonged hospitalization and early hospital readmission is undefined. Objectives To identify the most suitable immunosuppression regimen for inclusion in ERAS programs in order to minimize early ACR after LT and to provide expert panel recommendations Data sources Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. Methods Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Studies from January 2000 onward focusing on early ACR were included. Rates of early renal dysfunction and infection were evaluated. CRD42021245586 Results Thirty‐seven studies met inclusion criteria; 23 randomized controlled trials, 14 retrospective or prospective observational comparative or noncomparative studies. Several sources of biases which potentially confound conclusions were identified: heterogeneity in immunosuppression protocols, higher serum tacrolimus levels than currently used in clinical practice, differences in the definition of ACR. Conclusions Tacrolimus is the standard immunosuppression after LT and can be used in combination with other drugs such as corticosteroids and MMF, and in association with anti‐IL2 receptor antibody (IL2Ra) induction. (Quality of Evidence; Low | Grade of Recommendation; Strong). Low dose or delayed introduction of tacrolimus in association with corticosteroids and MMF and/or anti‐IL2Ra induction can be used to reduce acute kidney injury. (Quality of Evidence; Low | Grade of Recommendation; Strong). Use of tacrolimus in association with corticosteroids and MMF and/or anti‐IL2Ra induction does not lead to increased infection rates. (Quality of Evidence; Low | Grade of Recommendation; Weak)