唑类抗真菌药物致药物性肝损伤50例分析Δ
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摘要
目的:了解唑类抗真菌药物致药物性肝损伤的现状,探讨有效的防治措施,为临床安全、合理使用唑类抗真菌药物提供参考。方法:收集1989年1月-2014年12月我国公开发表的医药学期刊中有关唑类抗真菌药物致药物性肝损伤的个案报道,对唑类抗真菌药物致药物性肝损伤患者的年龄、性别、药品名称、用法用量、出现症状时间、转归等情况进行统计、分析。结果:共收集到相关文献36篇共50例个案报道,包括酮康唑致肝损伤29例(58%)、氟康唑致肝损伤9例(18%)、伊曲康唑致肝损伤8例(16%)、伏立康唑致肝损伤4例(8%)。药物性肝损伤患者的肝损伤与患者年龄、性别、用药疗程不相关,治愈率为88%。转归较差的患者6例(12%),其中4例经治疗无效死亡,2例因病情危重放弃治疗。因联合用药致药物性肝损伤的患者2例。结论:患者在服用唑类抗真菌药物时应定期检测肝功能和监测血药浓度,有条件时行基因检测,可降低肝损伤风险。确诊的药物性肝损伤患者应立即停药,及时进行退黄、降酶等保肝治疗或人工肝血浆置换、肝移植等手术治疗。
OBJECTIVE:To investigate the situation of drug-induced liver injury caused by azole antifungal drug and discuss effective prevention and treatment measures,to provide reference for safe and rational use of azole antifungal drug in the clinic.METHODS:Drug-induced liver injury caused by azole antifungal drug were collected from published medical and pharmaceutical periodicals in China during Jan.1989-Dec. 2014,and then analyzed statistically in respects of patient's age and gender,drug name,usage and dosage,onset time,outcome,etc. RESULTS:A total of 36 literatures were collected,involving 50 cases. Drug-induced liver injury were not related to patient's age, gender and treatment duration with cure rate of 88%. There were 29 cases of ketoconazole-induced liver injury(58%),9 cases of fluconazol-induced liver injury(18%),8 cases of itraconazole-induced liver injury(16%)and 4 cases of voriconazole-induced liver injury(8%). There were 6 cases of poor outcome(12%),of which 4 patients died due to treatment failure and 2 patients gave up treatment because of critical condition. 2 patients suffered from drug-induced liver injury caused by drug combination. CONCLUSIONS:Regular liver function detection and drug concentration monitoring should be provided for the patients when they use azole antifungal drug,and gene detection should be conducted when avalilable to reduce the risk of liver injury. The patients diagnosed as drug-induced liver injury should stop taking medicine immediately and receive supportive liver protection therapy as removing jaundice,enzyme reduction,artificial liver plasma exchange,liver transplantation and other surgery.
OBJECTIVE:To investigate the situation of drug-induced liver injury caused by azole antifungal drug and discuss effective prevention and treatment measures,to provide reference for safe and rational use of azole antifungal drug in the clinic.METHODS:Drug-induced liver injury caused by azole antifungal drug were collected from published medical and pharmaceutical periodicals in China during Jan.1989-Dec. 2014,and then analyzed statistically in respects of patient's age and gender,drug name,usage and dosage,onset time,outcome,etc. RESULTS:A total of 36 literatures were collected,involving 50 cases. Drug-induced liver injury were not related to patient's age, gender and treatment duration with cure rate of 88%. There were 29 cases of ketoconazole-induced liver injury(58%),9 cases of fluconazol-induced liver injury(18%),8 cases of itraconazole-induced liver injury(16%)and 4 cases of voriconazole-induced liver injury(8%). There were 6 cases of poor outcome(12%),of which 4 patients died due to treatment failure and 2 patients gave up treatment because of critical condition. 2 patients suffered from drug-induced liver injury caused by drug combination. CONCLUSIONS:Regular liver function detection and drug concentration monitoring should be provided for the patients when they use azole antifungal drug,and gene detection should be conducted when avalilable to reduce the risk of liver injury. The patients diagnosed as drug-induced liver injury should stop taking medicine immediately and receive supportive liver protection therapy as removing jaundice,enzyme reduction,artificial liver plasma exchange,liver transplantation and other surgery.
引文
[1]张宇平,崔健.1 108株深部真菌医院感染耐药性分析[J].中华医院感染学杂志,2010,20(8):1 186.
[2]张玉韩,孙彩云.里素劳致肝脏损害2例[J].中国医刊,1991,2(7):53.
[3]金祖余,傅得兴.酮康唑引起的中毒性肝炎[J].中国药学杂志,1991,26(7):423.
[4]徐慧珍,陈冠蓉.酮康唑引起的药物性肝炎4例[J].医药导报,1992,11(3):26.
[5]盛士芳,郑立农.酮康唑引起肝损害和男性乳房女性化1例[J].药学实践杂志,1992,10(1):67.
[6]朱瑞龙,胡和平,陈士葆.酮康唑性肝炎1例报告[J].第二军医大学学报,1993,14(2):142.
[7]逄晓云,刘晓琰,沈金芳.酮康唑致严重肝损1例[J].中国医院药学杂志,2009,29(18):1 579.
[8]余玉娥.酮康唑引起严重肝损伤1例[J].中国社区医师,1994,8(5):41.
[9]满辉.酮康唑引发亚急性肝坏死[J].药物不良反应杂志,2007,9(3):208.
[10]任一鸣,何琦娜,冯子坛.酮康唑致中毒性肝炎1例报告[J].胃肠病学和肝病学杂志,1995,4(3):219.
[11]余进东,罗斌.再次服里素劳(酮康唑)片致严重肝损害1例[J].健康大视野:医学分册,2006,2(3):13.
[12]计叔钧,梁扩寰.酮康唑所致之药物性肝损害:附2例报告及24例综合分析[J].胃肠病学和肝病学杂志,1995,4(3):204.
[13]宋荷玲.酮康唑致中毒性肝炎并发多器官损害的护理[J].华北煤炭医学院学报,2002,4(4):499.
[14]郭新云,万龙江,石黎明,等.酮康唑致肝损伤伴粒细胞减少2例[J].新医学,1996,27(2):73.
[15]阎双缓,吕胜益,封会茹.酮康唑致肝损害1例[J].河北医科大学学报,2001,2(4):88.
[16]张沈英.口服酮康唑致肝损害低蛋白血症1例[J].中国新药杂志,2003,12(5):354.
[17]崔淮西.酮康唑引起肝脏损伤1例[J].蚌埠医学院学报,1996,21(1):26.
[18]付红刚,张天.酮康唑致急性肝损害死亡[J].药物不良反应杂志,2001,3(3):159.
[19]郑韵.酮康唑用于HBs Ag阳性者致急性重症肝损伤1例报告[J].江西医学院学报,1995,35(2):62.
[20]潘慧云.酮康唑引起急性肝损害1例[J].中国现代应用药学,1994,11(5):51.
[21]裘雨林,裘怿剑.酮康唑致急性重症肝损伤1例报告[J].临床肝胆病杂志,1994,10(2):114.
[22]余秉翔,徐萍,王淑敏,等.氟康唑致药物性肝病1例[J].北京医学,1995,17(5):272.
[23]谢志宏.口服氟康唑引起药疹及肝功能异常2例[J].中国皮肤性病学杂志,1996,10(6):381.
[24]米润昭,孙晓云,耿素辉,等.氟康唑引起急性药物性肝炎[J].药物不良反应杂志,2002,4(1):28.
[25]卞长旺,丁元江,刘东科.氟康唑致肝损害1例报告[J].皮肤病与性病,2005,27(4):57.
[26]刘俊平,魏学兰,孙宏伟.氟康唑静脉注射致肝病毒性反应1例[J].医药产业资讯,2005,2(23):154.
[27]兰安杰,丁春雷,罗静.氟康唑注射液与华法林片合用致药物性肝损伤及凝血功能异常1例[J].中国药物警戒,2011,8(1):61.
[28]马丽娜,冀冰心,赵弘,等.氟康唑致严重肝功能损害1例[J].药物流行病学杂志,2010,19(9):540.
[29]徐锦龙,胡东军,陈武,等.氟康唑致急性肝损害1例[J].实用药物与临床,2013,16(9):882.
[30]袁浩龙.伊曲康唑致肝损害[J].药学进展,1993,17(1):57.
[31]骆予侬,方海丹.伊曲康唑致肝损害[J].医药导报,1998,17(2):81.
[32]郭龙,郑琳琴.伊曲康唑胶囊引起中毒性肝炎1例[J].海峡药学,1999,11(2):71.
[33]曹传梅.伊曲康唑胶囊引起肝炎[J].药物不良反应杂志,2005,7(4):314.
[34]曲彩虹,雷姿颖.伏立康唑与埃索美拉唑联用致乙肝肝硬化并肺部侵袭性真菌感染患者横纹肌溶解症[J].今日药学,2011,21(11):686.
[35]阎维维,张永莉.临床药师对1例伏立康唑致肝损害的脑血管病患者的药学监护[J].中国药房,2012,23(34):3 260.
[36]李国栋,刘震,冯端浩.伏立康唑致CYP2C19慢代谢型患者肝损害1例[J].药物流行病学杂志,2012,21(9):463.
[37]蔡小军,宋惠珠,赵敏.伏立康唑致严重肝损害1例[J].中国临床药理学杂志,2013,29(10):795.
[38]Hoofnagle JH.Drug-induced liver injury network[J].Hepatology,2004,40(4):773.
[39]Benichou C.Criteria of drug-induced liver disorders:report of an international consensus meeting[J].J Hepatol,1990,11(2):272.
[40]Bjornsson E,Davidsdottir L.The long-term follow-up affter idiosyncratic drug-induced liver injury with jaundice[J].J Hepatol,2009,30(3):511.
[41]Czaja AJ.Drug-induced autoimmune-like hepatitis[J].Dig Dis Sci,2011,56(4):958.
[42]Weiss J,Ten Hoevel MM,Burhenne J,et al.CYP2C19genotype is a major factor contributing to the highly variable pharmacokinetics of voriconazole[J].J Clin Pharmacol,2009,9(2):196.
[43]于乐成,陈成伟.药物性肝损伤[J].肝脏,2008,13(3):238.
[44]翁心华,朱利平.重视抗真菌药物的肝脏安全性[J].国际流行病学传染病学杂志,2008,35(3):147.
[2]张玉韩,孙彩云.里素劳致肝脏损害2例[J].中国医刊,1991,2(7):53.
[3]金祖余,傅得兴.酮康唑引起的中毒性肝炎[J].中国药学杂志,1991,26(7):423.
[4]徐慧珍,陈冠蓉.酮康唑引起的药物性肝炎4例[J].医药导报,1992,11(3):26.
[5]盛士芳,郑立农.酮康唑引起肝损害和男性乳房女性化1例[J].药学实践杂志,1992,10(1):67.
[6]朱瑞龙,胡和平,陈士葆.酮康唑性肝炎1例报告[J].第二军医大学学报,1993,14(2):142.
[7]逄晓云,刘晓琰,沈金芳.酮康唑致严重肝损1例[J].中国医院药学杂志,2009,29(18):1 579.
[8]余玉娥.酮康唑引起严重肝损伤1例[J].中国社区医师,1994,8(5):41.
[9]满辉.酮康唑引发亚急性肝坏死[J].药物不良反应杂志,2007,9(3):208.
[10]任一鸣,何琦娜,冯子坛.酮康唑致中毒性肝炎1例报告[J].胃肠病学和肝病学杂志,1995,4(3):219.
[11]余进东,罗斌.再次服里素劳(酮康唑)片致严重肝损害1例[J].健康大视野:医学分册,2006,2(3):13.
[12]计叔钧,梁扩寰.酮康唑所致之药物性肝损害:附2例报告及24例综合分析[J].胃肠病学和肝病学杂志,1995,4(3):204.
[13]宋荷玲.酮康唑致中毒性肝炎并发多器官损害的护理[J].华北煤炭医学院学报,2002,4(4):499.
[14]郭新云,万龙江,石黎明,等.酮康唑致肝损伤伴粒细胞减少2例[J].新医学,1996,27(2):73.
[15]阎双缓,吕胜益,封会茹.酮康唑致肝损害1例[J].河北医科大学学报,2001,2(4):88.
[16]张沈英.口服酮康唑致肝损害低蛋白血症1例[J].中国新药杂志,2003,12(5):354.
[17]崔淮西.酮康唑引起肝脏损伤1例[J].蚌埠医学院学报,1996,21(1):26.
[18]付红刚,张天.酮康唑致急性肝损害死亡[J].药物不良反应杂志,2001,3(3):159.
[19]郑韵.酮康唑用于HBs Ag阳性者致急性重症肝损伤1例报告[J].江西医学院学报,1995,35(2):62.
[20]潘慧云.酮康唑引起急性肝损害1例[J].中国现代应用药学,1994,11(5):51.
[21]裘雨林,裘怿剑.酮康唑致急性重症肝损伤1例报告[J].临床肝胆病杂志,1994,10(2):114.
[22]余秉翔,徐萍,王淑敏,等.氟康唑致药物性肝病1例[J].北京医学,1995,17(5):272.
[23]谢志宏.口服氟康唑引起药疹及肝功能异常2例[J].中国皮肤性病学杂志,1996,10(6):381.
[24]米润昭,孙晓云,耿素辉,等.氟康唑引起急性药物性肝炎[J].药物不良反应杂志,2002,4(1):28.
[25]卞长旺,丁元江,刘东科.氟康唑致肝损害1例报告[J].皮肤病与性病,2005,27(4):57.
[26]刘俊平,魏学兰,孙宏伟.氟康唑静脉注射致肝病毒性反应1例[J].医药产业资讯,2005,2(23):154.
[27]兰安杰,丁春雷,罗静.氟康唑注射液与华法林片合用致药物性肝损伤及凝血功能异常1例[J].中国药物警戒,2011,8(1):61.
[28]马丽娜,冀冰心,赵弘,等.氟康唑致严重肝功能损害1例[J].药物流行病学杂志,2010,19(9):540.
[29]徐锦龙,胡东军,陈武,等.氟康唑致急性肝损害1例[J].实用药物与临床,2013,16(9):882.
[30]袁浩龙.伊曲康唑致肝损害[J].药学进展,1993,17(1):57.
[31]骆予侬,方海丹.伊曲康唑致肝损害[J].医药导报,1998,17(2):81.
[32]郭龙,郑琳琴.伊曲康唑胶囊引起中毒性肝炎1例[J].海峡药学,1999,11(2):71.
[33]曹传梅.伊曲康唑胶囊引起肝炎[J].药物不良反应杂志,2005,7(4):314.
[34]曲彩虹,雷姿颖.伏立康唑与埃索美拉唑联用致乙肝肝硬化并肺部侵袭性真菌感染患者横纹肌溶解症[J].今日药学,2011,21(11):686.
[35]阎维维,张永莉.临床药师对1例伏立康唑致肝损害的脑血管病患者的药学监护[J].中国药房,2012,23(34):3 260.
[36]李国栋,刘震,冯端浩.伏立康唑致CYP2C19慢代谢型患者肝损害1例[J].药物流行病学杂志,2012,21(9):463.
[37]蔡小军,宋惠珠,赵敏.伏立康唑致严重肝损害1例[J].中国临床药理学杂志,2013,29(10):795.
[38]Hoofnagle JH.Drug-induced liver injury network[J].Hepatology,2004,40(4):773.
[39]Benichou C.Criteria of drug-induced liver disorders:report of an international consensus meeting[J].J Hepatol,1990,11(2):272.
[40]Bjornsson E,Davidsdottir L.The long-term follow-up affter idiosyncratic drug-induced liver injury with jaundice[J].J Hepatol,2009,30(3):511.
[41]Czaja AJ.Drug-induced autoimmune-like hepatitis[J].Dig Dis Sci,2011,56(4):958.
[42]Weiss J,Ten Hoevel MM,Burhenne J,et al.CYP2C19genotype is a major factor contributing to the highly variable pharmacokinetics of voriconazole[J].J Clin Pharmacol,2009,9(2):196.
[43]于乐成,陈成伟.药物性肝损伤[J].肝脏,2008,13(3):238.
[44]翁心华,朱利平.重视抗真菌药物的肝脏安全性[J].国际流行病学传染病学杂志,2008,35(3):147.