Acute liver failure related to fluconazole and voriconazole

A 2 months and 14 day old boy was hospitalized for drug eruptions and pneumonia. He received an IV infusion of fluconazole 24 mg twice daily because of Candida albicans positive in sputum culture, and plasma 1-3-beta-D dextran 324 ng/L during the processes of anti-infection and anti-allergic treatment. The boy's liver function was normal and the abdominal ultrasound examination had no abnormality seen before taking fluconazole. On day 5 after administration of fluconazole, the boy developed new rash on the mouth and lower limbs, moderate xanthochromia, pitting edema of skin over the whole body, and obvious abdominal distension after eating foods. Laboratory test showed alanine aminotransferase (ALT) 579 U/L, aspartate aminotransferase (AST) 655 U/L, total bilirubin (TBil) 71.9 μmol/L, direct bilirubin direct(DBil) 48.7 μmol/L, and alkaline phosphatase (ALP) 89 U/L on day 6 after administration of fluconazole. Ultrasound examination showed hepatomegaly and strong echo of strip in right hepatic lobe. On day 7, fluconazole was replaced by IV infusion of voriconazole 28 mg diluted in 5% glucose 15 ml twice daily. On the second day of using voriconazole, laboratory tests revealed the following results: ALT 761 U/L, AST 717 U/L, TBil 132.3μmol/L, DBil 112.4 μmol/L, ALP 104 U/L, prothrombin time 57 s, partially activated prothrombin 88 s, international normalized ratio 4.86, blood ammonia 79 μmol/L and lactic acid 6.5mmol/L. The patient was diagnosed as liver failure. Voriconazole was stopped. The boy received the symptomatic treatments which including liver-protecting and cholagogue agents, reducing blood ammonia, supplying coagulation factors, and 2 times of plasmapheresis. The boy was suggested to consider liver transplantation, because of his liver function had no significant improvement during the 5 days' treatment. His parents gave up the treatment and discharged by themselves. The boy was died on the second day of discharging which known from follow-up. Key words: Fluconazole; Voriconazole; Liver failure, acute; Infant