氟康唑与伏立康唑相关婴儿急性肝衰竭

Acute liver failure related to fluconazole and voriconazole

1例2个月14 d男性患儿因药疹、肺炎入院，抗过敏和抗感染治疗过程中因痰培养检出白色念珠菌、血浆1-3-β-D葡聚糖为324 ng/L而加用氟康唑24 mg、2次/d静脉滴注。加药前患儿肝功能正常，腹部超声检查未见异常。应用氟康唑第5天，患儿口唇、双下肢出现新发皮疹，皮肤中度黄染，全身凹陷性水肿，进食后腹胀明显；第6天患儿ALT 579 U/L，AST 655 U/L，TBil 71.9 μmol/L，DBil 48.7 μmol/L，ALP89 U/L；超声检查示肝脏肿大，肝右叶内可见条状强回声。第7天停用氟康唑，换用伏立康唑28 mg入5%葡萄糖注射液15 ml、2次/d 静脉滴注。换药次日患儿ALT 761 U/L，AST 717 U/L，TBil 132.3 μmol/L，DBil 112.4 μmol/L，ALP 104 U/L，凝血酶原时间57 s，部分活化凝血酶原88 s，INR 4.86，血氨79 μmol/L，乳酸6.5 mmol/L。诊断：急性肝衰竭。停用伏立康唑，给予保肝利胆、降血氨、补充凝血因子等对症治疗，并行血浆置换2次。经5 d救治患儿肝功能无明显好转，建议行肝移植，患儿家属放弃治疗，自动出院。随访得知患儿出院后第2天死亡。

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.