Antifungal Prophylaxis in Liver Transplantation: A Systematic Review and Network Meta‐Analysis

• Published in: American journal of transplantation Vol. 14; no. 12; pp. 2765 - 2776
• Main Authors: Evans, J. D. W., Morris, P. J., Knight, S. R.
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley 01.12.2014; Wiley Subscription Services, Inc
• Subjects: Antibiotic Prophylaxis; antibiotic: antifungal; Antifungal Agents - therapeutic use; Biological and medical sciences; Clinical research; complication: infectious; fungal; Graft Rejection - etiology; Graft Rejection - prevention & control; Health risk assessment; hepatology; Humans; infection and infectious agents; infectious disease, liver transplantation; Liver; Liver Diseases - surgery; Liver Transplantation - adverse effects; Liver, biliary tract, pancreas, portal circulation, spleen; Medical sciences; Meta-analysis; Mortality; Mycoses - microbiology; Mycoses - prevention & control; Postoperative Complications; practice, health services and outcomes research; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Transplants & implants; Chemoprophylaxis; Treatment; Digestive system; Surgery; Liver; Network; Graft; Systematic review; Homotransplantation; Metaanalysis; Liver transplantation; fungal; hepatology; infectious disease, liver transplantation; meta-analysis; Clinical research; antibiotic: antifungal; infection and infectious agents; practice, health services and outcomes research; complication: infectious
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/ajt.12925

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. This systematic review and network meta‐analysis demonstrates that fluconazole and liposomal amphotericin B are equally effective agents for antifungal prophylaxis in liver transplant recipients, and both are superior to itraconazole or no prophylaxis.