Hunt Christine M, Yuen Nancy A, Stirnadel-Farrant Heide A, Suzuki Ayako
Division of Gastroenterology, Duke University Medical Center, Durham, NC, United States; Durham Veterans Administration Medical Center, Durham, NC, United States.
Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, Research Triangle Park, NC, United States.
Regul Toxicol Pharmacol. 2014 Nov;70(2):519-26. doi: 10.1016/j.yrtph.2014.09.007. Epub 2014 Sep 16.
BACKGROUND/AIMS: Age-differences in the frequency and manifestations of drug-induced liver injury are not fully characterized. Data-mining analyses were performed to assess the impact of age on liver event reporting frequency with different phenotypes and agents.
236 drugs associated with hepatotoxicity were evaluated using the Empirical Bayes Geometric Mean (EBGM) of the relative reporting ratio with 90% confidence interval (EB05 and EB95) calculated for the age groups: 0-17, 18-64, and⩾65years (or elderly), for overall, serious (acute liver failure), hepatocellular, and cholestatic liver injury, using the WHO Safety Report Database.
Overall, cases of age 0-17, 18-64, and 65years or older comprised 6%, 62%, and 32% of liver event reports. Acute liver failure and hepatocellular injury were more frequently reported among children compared to adults and the elderly while reports with cholestatic injury were more frequent among the elderly (p<0.00001). A potential to cause mitochondrial dysfunction was more prevalent among the drugs with increased pediatric reporting frequency while high lipophilicity and biliary excretion were more common among the drugs associated with higher reporting frequency in the elderly.
Age-specific phenotypes and potential drug properties associated with age-specific hepatotoxicity were identified in reported liver events; further analyses are warranted.
背景/目的：药物性肝损伤的频率和表现的年龄差异尚未完全明确。进行数据挖掘分析以评估年龄对不同表型和药物的肝脏事件报告频率的影响。
使用世界卫生组织安全报告数据库，对236种与肝毒性相关的药物进行评估，计算0 - 17岁、18 - 64岁和≥65岁（或老年人）年龄组的相对报告率的经验贝叶斯几何均值（EBGM）及其90%置信区间（EB05和EB95），用于总体、严重（急性肝衰竭）、肝细胞性和胆汁淤积性肝损伤。
总体而言，0 - 17岁、18 - 64岁和65岁及以上的病例分别占肝脏事件报告的6%、62%和32%。与成人和老年人相比，儿童急性肝衰竭和肝细胞损伤的报告更为频繁，而胆汁淤积性损伤的报告在老年人中更为频繁（p<0.00001）。在儿科报告频率增加的药物中，导致线粒体功能障碍的可能性更为普遍，而在老年人报告频率较高的药物中，高亲脂性和胆汁排泄更为常见。
在报告的肝脏事件中确定了与年龄特异性肝毒性相关的年龄特异性表型和潜在药物特性；有必要进行进一步分析。
