title: Voriconazole hepatotoxicity in severe liver dysfunction.
abstract: There are no studies regarding to these effects in patients with severe liver dysfunction.
  
  
  OBJECTIVE
  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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Liver Intensive Therapy Unit, Institute of Liver Studies, Kings College Hospital of London, United Kingdom. pablo.a.solis@hotmail.com
authors.forename: Pablo
authors.initials: P
authors.lastname: Solís-Muñoz
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: López
authors.forename: William
authors.initials: W
authors.lastname: Bernal
authors.forename: Christopher
authors.initials: C
authors.lastname: Willars
authors.forename: Ana
authors.initials: A
authors.lastname: Verma
authors.forename: Michael A
authors.initials: MA
authors.lastname: Heneghan
authors.forename: Julia
authors.initials: J
authors.lastname: Wendon
authors.forename: Georg
authors.initials: G
authors.lastname: Auzinger
mesh_terms: D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000009:adverse effects / Q000627:therapeutic use; D000704:Analysis of Variance; D000935:Antifungal Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy / Q000453:epidemiology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D019370:Observation; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D014230:Triazoles / Q000009:adverse effects* / Q000627:therapeutic use; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; C068538:liposomal amphotericin B; D000666:Amphotericin B; D065819:Voriconazole