儿童药物性肝损伤的用药分析及临床特征

张艳芳; 郭玉明; 牛明; 葛斐林; 景婧; 朱云; 朱世殊; 韩紫欣; 王伽伯; 刘士敬; 肖小河

doi:10.3969/j.issn.1001-5256.2019.03.025

儿童药物性肝损伤的用药分析及临床特征

DOI: 10.3969/j.issn.1001-5256.2019.03.025

1. 承德医学院
2. 解放军总医院第五医学中心全军中医药研究所
3. 解放军总医院第五医学中心中西医结合诊疗与研究中心
4. 解放军总医院第五医学中心青少年肝病科

基金项目:

基于临床病证的传统无毒中药肝毒性客观辨识及机制研究(81630100)；国家中医药管理局中医药行业科研专项(201507004-4-2)；国家“重大新药创制”科技重大专项(2015ZX09501-004-001-008)；

详细信息

中图分类号: R725.7
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出版历程
- 出版日期: 2019-03-20

Drug-induced liver injury in children:An analysis of medication and clinical features

Chengde Medical College

Research funding:

摘要

摘要:
目的探讨导致儿童药物性肝损伤（DILI）的损肝药物及其发生的相关危险因素,为儿童临床安全用药提供参考。方法对解放军总医院第五医学中心2008年1月-2017年12月187例0～14岁儿童DILI的用药史、生化指标、症状体征及临床转归等进行回顾性分析。采用整合证据链法将其中127例可获取用药信息的DILI病例分为西药致DILI组（西药组,n=75）、中药致DILI组（中药组,n=15）及中西药联用致DILI组（中西药联用组,n=37）。比较不同组间的用药原因、用药时间和潜伏期、药物分类的差异。偏态分布的计量资料多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Nemenyi检验,计数资料组间比较采用χ2检验。结果重度及重度以上肝损伤的儿童DILI有116例,占全部病例的62%（116/187）,其中肝移植3例,死亡1例,45例（24%）发生慢性化。西药组和中西药联用组的可疑损肝西药均以抗菌药和解热镇痛抗炎药为主,分别占各组的42%和30%、56%和31%。中药组的可疑损肝药物以治疗皮肤病的中药为主,占中药组的47%,且主要为何首乌制剂（33%）。3组间用药时间（H=1...
- 药物性肝损伤 /
- 儿童 /
- 用药分析
Abstract:
Objective To investigate the drugs responsible for drug-induced liver injury ( DILI) in children and related risk factors, andto provide a reference for safe drug use in children in clinical practice. Methods A retrospective analysis was performed for the clinical da-ta of 187 children with DILI, aged 0-14 years, who were treated in The Fifth Medical Center of Chinese PLA General Hospital from January2008 to December 2017, including medication history, biochemical parameters, symptoms/signs, and clinical outcome. Based on the meth-od of integrated evidence chain, 127 children with medication information were divided into Western medicine-induced DILI group ( West-ern medicine group with 75 children) , traditional Chinese medicine ( TCM) -induced DILI group ( TCM group with 15 children) , and thegroup with DILI induced by Western medicine and TCM ( TCM-Western medicine group with 37 children) . The reason for medication, medication time, latency of DILI, and drug classification were compared between groups. The Kruskal-Wallis H test was used for compari-son of continuous data with skewed distribution between multiple groups, and the Nemenyi test was used for further comparison between twogroups; the chi-square test was used for comparison of categorical data between groups. Results Of all 187 children with DILI, 116 ( 62%) had severe liver injury or above, among whom 3 underwent liver transplantation and 1 died, and 45 ( 24%) developed chronicity.In the Western medicine group and the TCM-Western medicine group, major suspected drugs for DILI were antibiotics, antipyretics, anal-gesics, and anti-inflammatory drugs, which accounted for 42%, 30%, 56%, and 31%, respectively. In the TCM group, the most com-mon TCM drugs for DILI were those used to treat skin diseases, which accounted for 47% and were mainly the preparations of Fallopia multi-flora ( 33%) . There were significant differences between the three groups in medication time ( H = 11. 658, P = 0. 003) and latency ( H =10. 945, P = 0. 004) , and the TCM group had significantly longer medication time and latency than the other two groups ( all P < 0. 05) .Conclusion Most children with DILI have serious conditions. The risk of liver injury due to medication in children should be taken serious-ly, and particular emphasis should be placed on the risk of liver injury caused by antibiotics, antipyretics, analgesics, and anti-inflamma-tory drugs and long-term use of some TCM drugs for skin diseases.
- drug-induced liver injury /
- children /
- medication analysis

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参考文献(20)

[1] Drug-induced Liver Disease Study Group, Chinese Society ofHepatology, Chinese Medical Association. Guidelines for themanagement of drug-induced liver injury[J]. J Clin Hepatol, 2015, 31 (11) :1752-1769. (in Chinese) 中华医学会肝病学分会药物性肝病学组.药物性肝损伤诊治指南[J].临床肝胆病杂志, 2015, 31 (11) :1752-1769.

[2] GAN Y, DONG Y, ZHANG HF, et al. Clinical characteristicsand outcomes of drug-induced liver injury in children:Astudy of 184 cases[J]. J Clin Hepatol, 2015, 31 (8) :1244-1247. (in Chinese) 甘雨, 董漪, 张鸿飞, 等. 184例儿童药物性肝损伤的临床特征及转归状况评价[J].临床肝胆病杂志, 2015, 31 (8) :1244-1247.

[3] AMIN MD, HARPAVAT S, LEUNG DH, et al. Drug-inducedliver injury in children[J]. Curr Opin Pediatr, 2015, 27 (5) :625-633.

[4] FAA G, EKSTROM J, CASTAGNOLA M, et al. A developmen-tal approach to drug-induced liver injury in newborns andchildren[J]. Curr Med Chem, 2012, 19 (27) :4581-4594.

[5] ZHANG CP, MA Y. Analysis of 29 cases with drug-induced liverinjury in children[J]. J Pediatr Pharm, 2015, 21 (1) :44-47. (inChinese) 张长平, 马燕. 29例儿童药物性肝损伤临床分析[J].儿科药学杂志, 2015, 21 (1) :44-47.

[6] DU SX, LU LL, MIAO YX, et al. Features of children with drug-induced liver injury:An analysis of 34 cases[J]. J PracHepatol, 2016, 19 (5) :607-609. (in Chinese) 杜水仙, 卢琳琳, 苗英霞, 等.儿童药物性肝损伤34例分析[J].实用肝脏病杂志, 2016, 19 (5) :607-609.

[7] ZHU XX, WAN CM. Recent progress in management and treat-ment of drug-induced liver injury in children[J]. J Clin Hepa-tol, 2012, 28 (12) :896-898. (in Chinese) 朱欣欣, 万朝敏.儿童药物性肝损害[J].临床肝胆病杂志, 2012, 28 (12) :896-898.

[8] Branch of Hepatobiliary Diseases, China Association of Chi-nese Medicine, Branch of Chinese Patent Medicine, China As-sociation of Chinese Medicine. Guidelines for the clinical man-agement of herb-induced liver injury[J]. J Clin Hepatol, 2016, 32 (5) :835-843. (in Chinese) 中华中医药学会肝胆病分会, 中华中医药学会中成药分会.中草药相关肝损伤临床诊疗指南[J].临床肝胆病杂志, 2016, 32 (5) :835-843.

[9] WANG JB, MA ZJ, NIU M, et al. Evidence chain-basedcausality identification in herb-induced liver injury:Exemplifi-cation of a well-known liver-restorative herb Polygonum mul-tiflorum[J]. Front Med, 2015, 9 (4) :457-467.

[10] HE TT, ZHONG XW, ZHANG N, et al. Prospective clinicalstudy of 187 cases with liver damage caused by medicine andits preparations[J]. Chin Hepatol, 2018, 23 (8) :666-669. (in Chinese) 何婷婷, 钟学文, 张宁, 等. 187例中草药及其制剂导致肝损伤病例前瞻性临床研究[J].肝脏, 2018, 23 (8) :666-669.

[11] ZHU Y, LI YG, WANG JB, et al. Causes, features, and out-comes of drug-induced liver injury in 69 children from China[J]. Gut Liver, 2015, 9 (4) :525-533.

[12] CHALASANI N, FONTANA RJ, BONKOVSKY HL, et al. Cau-ses, clinical features, and out-comes from a prospectivestudy of drug-induced liver injury in the united states[J].Gastroenterology, 2008, 135 (6) :1924-1934.

[13] REN ZQ, WANG JH, GUO XY, et al. A review analysis of chi-nese literatures 2005-2014:Clinical features of drug-in-duced liver injury[J]. Chin J Pharmacoepidemiol, 2016, 25 (5) :284-289. (in Chinese) 任张青, 王进海, 郭晓燕, 等. 2005~2014年我国药物性肝损伤临床综合分析[J].药物流行病学杂志, 2016, 25 (5) :284-289.

[14] QI YB, QIU L, JIANG HL, et al. Clinical characteristics ofdrug-induced liver injury:An analysis of 394 cases[J]. JClin Hepatol, 2014, 30 (5) :438-441. (in Chinese) 祁亚宾, 邱玲, 姜红丽, 等.药物性肝损伤394例临床特点分析[J].临床肝胆病杂志, 2014, 30 (5) :438-441.

[15] YUAN L, YANG YG, SHEN YX, et al. Research advances indrug-induced liver injury[J]. J Clin Hepatol, 2017, 33 (2) :375-378. (in Chinese) 袁玲, 杨永耿, 沈有秀, 等.药物性肝损伤的研究进展[J].临床肝胆病杂志, 2017, 33 (2) :375-378.

[16] WANG L. Analysis of the disease composition and householdregistration of hospitalized children in Beijing[J]. Chin MedRecord, 2018, 19 (6) :35-37. (in Chinese) 王丽.北京市住院儿童疾病构成与户籍分析[J].中国病案, 2018, 19 (6) :35-37.

[17] SQUIRES RH Jr, SHNEIDER BL, BUCUVALAS J, et al. Acuteliver failure in children:The first 348 patients in the pediatric a-cute liver failure study group[J]. J Pediatr, 2006, 148 (5) :652-658.

[18] MURRAY KF, HADZIC N, WIRTH S, et al. Drug-related hep-atotoxicity and acute liver failure[J]. J Pediatr GastroenterolNutr, 2008, 47 (4) :395-405.

[19] ZHU Y, LIU SH, WANG JB, et al. Clinical analysis of drug-induced liver injury caused by Polygonum multiflorum and itspreparations[J]. Chin J Integr Tradl Western Med, 2015, 35 (12) :1442-1447. (in Chinese) 朱云, 刘树红, 王伽伯, 等.何首乌及其制剂导致药物性肝损伤的临床分析[J].中国中西医结合杂志, 2015, 35 (12) :1442-1447.

[20] HE TT, GONG M, BAI YF, et al. Clinical analysis of two diag-nosis methods for herb-induced liver injury[J]. China J ChinMater Med, 2016, 41 (16) :3096-3099. (in Chinese) 何婷婷, 宫嫚, 白云峰, 等. 2种药物性肝损伤诊断指南的应用分析[J].中国中药杂志, 2016, 41 (16) :3096-3099.

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