Voriconazole hepatotoxicity in severe liver dysfunction Pablo Solı ´s-Mu ~ noz*, Juan Carlos L  opez, William Bernal, Christopher Willars, Ana Verma, Michael A. Heneghan, Julia Wendon, Georg Auzinger Liver Intensive Therapy Unit, Institute of Liver Studies, Kings College Hospital of London, Denmark Hill, London SE5 9RS, United Kingdom Accepted 26 September 2012 Available online 3 October 2012 KEYWORDS Voriconazole; Hepatotoxicity; Invasive aspergillosis; Severe liver dysfunction; Liver transplantation Summary There are no studies regarding to these effects in patients with severe liver dys- function. Objectives: The aims of this study were to characterize voriconazole hepatotoxicity in patients with severe liver dysfunction and to compare it with a matched cohort treated with liposomal amphotericin B. Methods: This is an observational study, in which adults patients treated with at least 4 doses of voriconazole were included. Patients treated with liposomal amphotericin B were used as control group. Results: Sixty nine percent of patients treated with voriconazole showed changes in liver func- tion tests (LFTs) during therapy. They showed elevated transaminases in 35%, cholestasis in 15% or a combination of both in 45%. According to the CTC classification, all patients with hepato- toxicity had a severe reaction. The Roussel Uclaf Causality Assessment Method score in all pa- tients with hepatotoxicity was greater than 8. There was a correlation between initial loading dose greater than 300 mg (4.5 mg/kg) and the risk of hepatotoxicity (p < 0.001). The control group developed alterations in the LFTs in only 10.3% of patients. Conclusion: Voriconazole should be used with caution in patients with severe liver dysfunction and following liver transplantation, with frequent monitoring of LFTs or using liposomal am- photericin B instead. Crown Copyright ª 2012 Published by Elsevier Ltd on behalf of The British Infection Associa- tion. All rights reserved. Introduction Voriconazole is a triazole antifungal agent with broad activity against many common yeast and mould species. Recent guidelines of the Infectious Diseases Society of America recommend the use of voriconazole as the primary therapy for invasive aspergillosis (IA). 1 Voriconazole was more effective than amphotericin B deoxycholate as initial * Corresponding author. Tel.: þ44 7402303737. E-mail address: pablo.a.solis@hotmail.com (P. Solı ´s-Mu~ noz). 0163-4453/$36 Crown Copyright ª 2012 Published by Elsevier Ltd on behalf of The British Infection Association. All rights reserved. http://dx.doi.org/10.1016/j.jinf.2012.09.011 www.elsevierhealth.com/journals/jinf Journal of Infection (2013) 66, 80e86