CAJ | 학술논문

目的探讨难治性癫(癎)患儿在应用丙戊酸抗癫(癎)治疗过程中出现的与药物剂量无关的急性药物性肝损伤的临床表现及治疗经验,以提高诊治水平.方法对北京大学第一医院儿科2006年以来收治的4例在应用丙戊酸抗癫(癎)治疗过程中出现严重肝损伤的癫(癎)患儿的病例资料进行综合分析,包括癫(癎)发作年龄,服用丙戊酸时年龄,服用丙戊酸后出现肝损伤的时间、临床表现、辅助检查及相应治疗等.结果男3例,女1例,就诊年龄1岁～9岁1个月,就诊时癫(癎)病程25 d至6个月.临床上均表现为难以控制的持续性部分性癫(癎)发作,在应用丙戊酸后62 d(50 ～76 d)出现与用药剂量无关的、以合成功能障碍为主的严重肝损伤.3例临床诊断为Alpers综合征,其中1例证实存在POLG基因突变；1例脑活检病理诊断为星形胶质细胞瘤.全部病例除立即撤除丙戊酸并给予积极对症支持保肝治疗外,3例紧急使用静脉左旋肉碱,病情改善.结论丙戊酸所致的与用药剂量无关的严重肝损伤可首先表现为肝脏合成功能下降.难治性癫(癎)患儿在应用丙戊酸过程中,对于其肝毒性损害的监测,采用肝脏合成功能性试验,可能比肝酶学检查更有意义.突变基因检测和肝脏功能监测是降低丙戊酸所致药物性肝炎发生率的有效手段.早期静脉应用左旋肉碱治疗可使严重肝损伤患儿的预后得以改观.
목적 탐토난치성전(간)환인재응용병무산항전(간)치료과정중출현적여약물제량무관적급성약물성간손상적림상표현급치료경험,이제고진치수평.방법 대북경대학제일의원인과2006년이래수치적4례재응용병무산항전(간)치료과정중출현엄중간손상적전(간)환인적병례자료진행종합분석,포괄전(간)발작년령,복용병무산시년령,복용병무산후출현간손상적시간、림상표현、보조검사급상응치료등.결과 남3례,녀1례,취진년령1세～9세1개월,취진시전(간)병정25 d지6개월.림상상균표현위난이공제적지속성부분성전(간)발작,재응용병무산후62 d(50 ～76 d)출현여용약제량무관적、이합성공능장애위주적엄중간손상.3례림상진단위Alpers종합정,기중1예증실존재POLG기인돌변；1례뇌활검병리진단위성형효질세포류.전부병례제립즉철제병무산병급여적겁대증지지보간치료외,3례긴급사용정맥좌선육감,병정개선.결론 병무산소치적여용약제량무관적엄중간손상가수선표현위간장합성공능하강.난치성전(간)환인재응용병무산과정중,대우기간독성손해적감측,채용간장합성공능성시험,가능비간매학검사경유의의.돌변기인검측화간장공능감측시강저병무산소치약물성간염발생솔적유효수단.조기정맥응용좌선육감치료가사엄중간손상환인적예후득이개관.
Objective Children with refractory epilepsy who suffered from severe liver function impairment during valproic acid (VPA) treatment at routine dosage were studied.The clinical manifestations and therapeutic approaches were investigated in order to improve its diagnosis and management.Method Clinical information as well as features and management of 4 inpatients who were suffered from intractable epilepsy with severe liver function impairment induced by VPA since 2006 were collected and analyzed,including age of onset of epilepsy,VPA using age and the time when liver injury occurred,clinical manifestations,auxiliary examinations and management.Result Among the 4 cases,three were male and one was female.The admitted age ranged from 1-9 years and 1 month.The course of disease was 25 d-6 months.They manifested as refractory epilepsy of epilepsia partialis continua which was difficult to control.After using VPA for 62 d (50-76 d),all developed severe impairment of liver synthetic function which was not related to the concentration of VPA.One was diagnosed with Alpers syndrome,two were suspicious of Alpers syndrome,and the other was diagnosed gliocytoma after brain biopsy.VPA was stopped immediately and symptomatic therapies were used.Other than that,intravenous injection of L-carnitine in 3 cases recovered the liver function.Conclusion VPA-associated severe hepatotoxicity can manifest first as impaired liver synthetic function.Besides alanin transaminase and aspartate transaminase,the liver synthetic function test is more important than monitoring of liver enzymatic functions in monitoring for the hepatotoxicity.Intravenous injection of L-carnitine in early stage showed good treatment effect.