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Meta-Analysis
. 2021 Mar 8:76:e2597.
doi: 10.6061/clinics/2021/e2597. eCollection 2021.

Safety and effectiveness of mycophenolate mofetil associated with tacrolimus for liver transplantation immunosuppression: a systematic review and meta-analysis of randomized controlled trials

Francisco Tustumi  1 , Antonio Afonso de Miranda Neto  1 , Sérgio Silveira Júnior  1 , Felipe Alexandre Fernandes  1 , Miller Barreto de Brito E Silva  1 , Lucas Ernani  1 , Lucas Souto Nacif  1 , Fabricio Ferreira Coelho  1 , Wellington Andraus  1 , Wanderley Marques Bernardo  1 , Paulo Herman  1 , Luiz Augusto Carneiro-D'Albuquerque  1
Affiliations
Meta-Analysis

Safety and effectiveness of mycophenolate mofetil associated with tacrolimus for liver transplantation immunosuppression: a systematic review and meta-analysis of randomized controlled trials

Francisco Tustumi et al. Clinics (Sao Paulo). .

Abstract

A combination of immunosuppressants may improve outcomes due to the synergistic effect of their different action mechanisms. Currently, there is no consensus regarding the best immunosuppressive protocol after liver transplantation. This review aimed to evaluate the effectiveness and safety of tacrolimus associated with mycophenolate mofetil (MMF) in patients undergoing liver transplantation. We performed a systematic review and meta-analysis of randomized clinical trials. Eight randomized trials were included. The proportion of patients with at least one adverse event related to the immunosuppression scheme with tacrolimus associated with MMF was 39.9%. The tacrolimus with MMF immunosuppression regimen was superior in preventing acute cellular rejection compared with that of tacrolimus alone (risk difference [RD]=-0.11; p =0.001). The tacrolimus plus MMF regimen showed no difference in the risk of adverse events compared to that of tacrolimus alone (RD=0.7; p=0.66) and cyclosporine plus MMF (RD=-0.7; p=0.37). Patients undergoing liver transplantation who received tacrolimus plus MMF had similar adverse events when compared to patients receiving other evaluated immunosuppressive regimens and had a lower risk of acute rejection than those receiving in the monodrug tacrolimus regimen.

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Conflict of interest statement

No potential conflict of interest was reported.

Figures

Supplementary File 1
Supplementary File 1
Supplementary File 2
Supplementary File 2. Robins II. Risk of bias evaluation.
Supplementary File 3
Supplementary File 3. GRADE certainty assessment for comparison FK506 plus MMF vs. FK506 alone. CI: Confidence interval; RCT: randomized clinical trial; MMF: Mycophenolate mofetil; FK506: Tacrolimus; CyA: Cyclosporine; a. Studies with small sample size; b. Risk difference 95% CI>30%; c. Heterogeneity >80%
Supplementary File 4
Supplementary File 4. GRADE certainty assessment for comparison FK506 plus MMF vs. CyA plus MMF. CI: Confidence interval; RCT: randomized clinical trial; MMF: Mycophenolate mofetil; FK506: Tacrolimus; CyA: Cyclosporine; a. Studies with small sample size; b. Risk difference 95% CI>30%; c. Heterogeneity >80%.
Supplementary File 5
Supplementary File 5. Funnel plots for comparison FK506 plus MMF vs. FK506 alone. A) Graft loss; B) Acute rejection; C) Mortality; D) Infection; E) Adverse events; F) Acute kidney injury. Fixed effect model was used for A, B, and C; Random effect model was used for D and E.
Supplementary File 6
Supplementary File 6. Funnel plots for comparison FK506 plus MMF vs. CyA plus MMF. A) Graft loss; B) Acute rejection; C) Mortality; D) Infection; E) Adverse events. Fixed effect model was used for A, B, C, and D.
Figure 1
Figure 1. The risks of the FK506 plus MMF regimen on A) Graft loss; B) Acute rejection; C) Mortality; D) Adverse events.
Figure 2
Figure 2. The main hematological adverse events related to the FK506 plus MMF regimen usage. A) Anemia; B) Leukopenia; C) Thrombocytopenia.
Figure 3
Figure 3. The risks of the FK506 plus MMF regimen on A) Acute kidney injury; B) New onset diabetes; C) Infections; D) CMV infection; E) Nausea/Vomiting; F) Diarrhea.
Figure 4
Figure 4. FK506 plus MMF compared with FK506 in isolation. A) Graft loss; B) Acute rejection; C) Mortality; D) Infection; E) Adverse events; F) Acute kidney injury.
Figure 5
Figure 5. FK506 plus MMF compared with CyA plus MMF. A) Graft loss; B) Acute rejection; C) Mortality; D) Infection; E) Adverse events.
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