Antifungal prophylaxis in liver transplantation: a systematic review and network meta-analysis

Invasive fungal infections (IFIs) cause significant morbidity and mortality in liver transplant recipients, but the need and best agent for prophylaxis is uncertain. A comprehensive literature search was performed to identify randomized controlled trials comparing regimens for antifungal prophylaxis in liver transplant recipients. Direct comparisons were made between treatments using random-effects meta-analysis and a Bayesian network meta-analysis was performed for the primary end point of proven IFI. Fourteen studies met inclusion criteria, reporting comparisons of fluconazole, liposomal amphotericin B (L-AmB), itraconazole, micafungin and placebo. Overall, antifungal prophylaxis reduced the rate of proven IFI (odds ratio [OR] 0.37, confidence interval [CI] 0.19-0.72, p = 0.003), suspected or proven IFI (OR 0.40, CI 0.25-0.66, p = 0.0003) and mortality due to IFI (OR 0.32, CI 0.10-0.83, p = 0.02) when compared to placebo. All-cause mortality was not significantly affected. There was no difference in risk of adverse events requiring cessation of prophylaxis (OR 1.11, 95% CI 0.48-2.55, p = 0.81). In the network meta-analysis an equivalent reduction in the rate of IFI was seen with fluconazole (OR 0.21, CI 0.06-0.57) and L-AmB (OR 0.21, CI 0.05-0.71) compared with placebo. Routine prophylaxis with fluconazole or L-AmB reduces the incidence of IFI following liver transplantation, and the available evidence suggests that the two are equivalent in efficacy.