氟康唑治疗终末期肝病继发真菌感染患者的安全性评价  

The safety evaluation of fluconazole used in patients with end-stage liver disease complicated with fungal infection

作　　者：范春蕾[1] 张飞飞[1] 李磊[1] 陈阳琴[1] 张鑫[1] 董培玲[1] 丁惠国[1] 

机构地区：[1]首都医科大学附属北京佑安医院肝病消化中心,100069

出　　处：《北京医学》2014年第12期1035-1039,共5页Beijing Medical Journal

基　　金：北京市卫生系统高层次卫生技术人才培养计划(2011-2-19);北京市科学计划(D131100005313005);科技部国家国际科技合作专项项目(2012DFA30850)

摘　　要：目的 评价氟康唑应用于终末期肝病继发真菌感染患者的安全性。方法 回顾性分析2012年1月至2013年11月收治的64例终末期肝病继发真菌感染患者（失代偿期肝硬化27例、原发性肝癌21例、肝衰竭16例）的临床资料。氟康唑首剂0.4 g/d静脉滴注,之后0.2 g/d静脉滴注。记录患者的一般资料、临床表现、用药前及用药后每周的血常规、肝功能、肾功能、凝血功能等相关指标的变化。结果 氟康唑疗程4~62 d,中位时间为15 d,应用氟康唑第1、2、5、6周后患者血清（1,3）-β-D葡聚糖指标明显下降（P﹤0.05）。丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（T-BIL）、γ-谷氨酰转肽酶（GGT）、碱性磷酸酶（ALP）、总胆固醇（TC）、胆碱酯酶（CHE）用药前后无明显变化。肾功能指标尿素氮（BUN）、肌酐（Cr）及肾小球滤过率（e GFR）在用药前后无明显变化。血红蛋白在用药第3周后较用药前明显下降（P〈0.05）;血小板在用药8~14 d明显下降,其对数值为1.84±0.37,较用药前及其他时间的差异有统计学意义（P﹤0.05）。患者的凝血功能无明显变化。4例（6.25%）患者出现与氟康唑密切相关的不良反应,3例表现为恶心、呕吐,1例为腹泻,停药后恢复。结论 终末期肝病继发真菌感染患者应用氟康唑安全,不良反应发生少,未明显加重肝损伤,无明显肾毒性。应用超过1周需监测血象。Objective To evaluate the safety of fluconazole used in patients with end-stage liver disease complicated with fungal infection. Methods A retrospective analysis was conducted among 64 patients with end-stage liver disease （27 cases with decompensated cirrhosis, 21 cases with primary hepatocellular carcinoma and 16 cases with liver failure）, who complicated with fungal infection, from January 2012 to November 2013. Fluconazole （0.4 g/d） was administered in the first day of treatment, then 0.2 g daily. The patients demographic information, clinical manifestations, and laboratory examination indexes such as blood routine test, liver and renal function and coagulation function before and after the treatment were recorded. Results The treatment course was 4-62 d, and the median time was 15 d. After 1, 2, 5, 6 weeks of application of fluconazole, the serum （1,3） -beta glucan D decreased significantly. Before and after administration of flueonazole, liver function indexes （ALT, AST, T-BIL, GGT, ALP, CHE） and renal function indexes （BUN, Cr, glomerular filtration rate） didn＇t change obviously. Hemoglobin decreased significantly after 3 weeks of fluconazole administration （P 〈 0.05）. Platelets decreased significantly in 8-14 d during the treatment, the logarithmic value was 1.84±0.37 and then returned to the original level. Coagulation function tests did not change significantly after the treatment. A total of 4 patients experienced fluconazole related adverse reactions, in whom 3 had nausea and vomiting and 1 had diarrhea. Both of them recovered after drug withdrawal. Conclusion Fluconazole can be safely used in patients with end-stage liver disease complicated with fungal infection. There are few adverse reactions of fiuconazole. Fluconazole has little liver and kidney toxicity. When the application of fluconazole for more than 1 week, close monitoring of blood routine test is needed.

关 键 词：氟康唑 终末期肝病 真菌感染 (1 3)-β-D葡聚糖 

分 类 号：R575.3[医药卫生—消化系统] R519[医药卫生—内科学]