Characteristics of idiosyncratic drug-induced liver injury in children: results from the DILIN prospective study.
Characteristics of idiosyncratic drug-induced liver injury in children: results from the DILIN prospective study.
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DOI：
10.1097/mpg.0b013e31821d6cfd
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发表时间：
2011-08
影响因子：
2.9
通讯作者：
Drug-Induced Liver Injury Network
中科院分区：
文献类型：
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作者：
Molleston JP;Fontana RJ;Lopez MJ;Kleiner DE;Gu J;Chalasani N;Drug-Induced Liver Injury Network
儿童特殊药物性肝损伤(DILI)的范围和严重程度尚不清楚。DILIN(药物诱导肝损伤网络)前瞻性研究是一项纵向多中心研究，旨在确定可疑DILI的病因、危险因素和结局。2004年9月至2009年9月期间，对30名符合资格标准的2至18岁疑似患有帝力的儿童进行了登记和至少6个月的学习。平均年龄为14岁，其中70%是女孩。抗菌药物(50%)和中枢神经系统药物(40%)是最常见的药物类别，米诺环素、异烟肼、阿奇霉素、托莫西汀和拉莫三嗪是主要药物。从开始用药到出现症状的中位时间为32天。谷草转氨酶503U/L、丙氨酸氨基转移酶727U/L、碱性磷酸酶331U/L、总胆红素3.9 mg/dL。自身抗体常见(%)。肝损害类型：肝细胞性占78%，胆汁淤积型占13%，混合型占9%。DILI事件评分：轻度32%，中度44%，重度20%，死亡(6个月内)4%。因果关系评估肯定是36%，很可能是36%，可能是16%，可能是8%，而不太可能是4%。在6个月的随访中，7%的患者有持续性的肝脏测试异常，表明存在慢性DILI。12名儿童的肝脏活检最常见的是慢性肝炎或胆管损伤。儿童特发性DILI最常见的是由抗菌药物或中枢神经系统药物引起，通常表现为肝细胞损伤模式。大多数患者都康复了，但发病率和罕见的死亡率也很高。
The spectrum and severity of idiosyncratic drug-induced liver injury (DILI) in children are not well established. The DILIN (Drug-Induced Liver Injury Network) Prospective Study is a longitudinal multicenter study designed to determine the etiologies, risk factors, and outcomes of suspected DILI. Between September 2004 and September 2009, 30 children ages 2 to 18 years with suspected DILI who met eligibility criteria were enrolled and studied for at least 6 months. Mean age was 14 years; 70% were girls. Antimicrobial (50%) and central nervous system agents (40%) were the most commonly implicated drug classes, with minocycline, isoniazid, azithromycin, atomoxetine, and lamotrigine the leading agents. Median time from drug initiation to symptom onset was 32 days. Peak (median) liver chemistries were aspartate aminotransferase 503 U/L, alanine aminotransferase 727 U/L, alkaline phosphatase 331 U/L, and total bilirubin 3.9 mg/dL. Autoantibodies were common (64%). Liver injury pattern was hepatocellular 78%, cholestatic 13%, and mixed 9%. The DILI episode was scored: mild 32%, moderate 44%, severe 20%, and fatal (within 6 months) 4%. Causality assessment was definite 36%, very likely 36%, probable 16%, possible 8%, and unlikely 4%. Seven percent had persistent liver test abnormalities at 6-month follow-up suggesting chronic DILI. Liver biopsies from 12 children most frequently demonstrated chronic hepatitis or bile duct injury. Idiosyncratic DILI in children is most commonly caused by antimicrobial or central nervous system agents and usually presents with a hepatocellular injury pattern. The majority of patients recover, but morbidity and infrequent mortality are seen.