Voriconazole hepatotoxicity in severe liver dysfunction

Abstract

There are no studies regarding to these effects in patients with severe liver dysfunction. 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. 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. Sixty nine percent of patients treated with voriconazole showed changes in liver function 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 hepatotoxicity had a severe reaction. The Roussel Uclaf Causality Assessment Method score in all patients 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. Voriconazole should be used with caution in patients with severe liver dysfunction and following liver transplantation, with frequent monitoring of LFTs or using liposomal amphotericin B instead.