Phenotypic Characterization of Idiosyncratic Drug-Induced Liver Injury: The Influence of Age and Sex
Phenotypic Characterization of Idiosyncratic Drug-Induced Liver Injury: The Influence of Age and Sex
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DOI：
10.1002/hep.22895
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发表时间：
2009-06-01
期刊：
影响因子：
13.5
通讯作者：
Hidalgo, Ramon
中科院分区：
文献类型：
--
作者：
Isabel Lucena, M.;Andrade, Raul J.;Hidalgo, Ramon
年龄增加和女性是药物性肝毒性（DILI）的建议风险因素。我们研究了这些变量对发展DILI倾向的影响，以及其临床表现和结局。对1994年4月至2007年8月期间提交给西班牙登记处的所有DILI病例进行了分析。603例DILI病例（310例男性;平均年龄54岁）显示出相似的性别分布，在40- 49岁和60- 69岁年龄组中达到两个高峰。在20至29岁组中没有记录病例。年龄≥ 60岁的患者占病例的46%，男性占优势（158例男性，118例女性; P = 0.009），与年轻患者相反。年龄较大与胆汁淤积型损伤独立相关（1年年龄间隔的比值比：1.024 [95%置信区间：1.010-1.038];男性/女性比值为1：2; P = 0.001）和年龄较小的肝细胞损伤（比值比：0.983 [95%置信区间：0.972-0.994];女性/男性比值为1：2; P = 0.002）。在混合组中，年龄效应不明显。女性患者并发急性肝功能衰竭/肝移植的发生率较高（P < 0.01）。结论：老年和女性都不是整体DILI的易感因素。然而，年龄较大是胆汁淤积性损害的决定因素，男性占优势，而年龄较小与溶细胞性损害相关，女性比例较高。女性显然表现出最糟糕的结果。这些表型相关性的知识可以指导DILI的鉴别诊断和因果关系的归因。（肝脏学2009;49：2001-2009。）
Increased age and female sex are suggested risk factors for drug-induced hepatotoxicity (DILI). We studied the influence of these variables on the propensity to develop DILI, as well as its clinical expression and outcome. All cases of DILI submitted to the Spanish Registry between April 1994 and August 2007 were analyzed. Six hundred three DILI cases (310 men; mean age, 54 years) showed a similar sex distribution, reaching two peaks in the 40- to 49-year-old and 60- to 69-year-old age groups. No cases were recorded in the 20- to 29-year-old group. Patients aged >= 60 years accounted for 46% of the cases, with a male predominance (158 males, 118 females; P = 0.009), as opposed to younger patients. Older age was independently associated with cholestatic type of injury (odds ratio for an age interval for 1 year: 1.024 [95% confidence interval: 1.010-1.038]; male/female ratio, 1:2; P = 0.001) and younger age with hepatocellular damage (odds ratio: 0.983 [95% confidence interval: 0.972-0.994]; female/male ratio, 1:2; P = 0.002). In the mixed group, no age effect was evident. Outcome with fluminant liver failure/liver transplantation was more frequently encountered in women (P < 0.01). Conclusion: Neither older age nor female sex are predisposing factors to overall DILI. However, older age is a determinant for cholestatic damage with a male predominance, whereas younger age is associated with cytolytic damage and a female overrepresentation. Women distinctly exhibit the worst outcome. Knowledge of these phenotypic associations could guide differential diagnosis and attribution of causality in DILI. (HEPATOLOGY 2009;49:2001-2009.)