Hepatotoxicity associated with statins: Reports of idiosyncratic liver injury post-marketing
Hepatotoxicity associated with statins: Reports of idiosyncratic liver injury post-marketing
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DOI：
10.1016/j.jhep.2011.07.023
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发表时间：
2012-02-01
影响因子：
25.7
通讯作者：
Kalaitzakis, Evangelos
中科院分区：
文献类型：
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作者：
Bjornsson, Einar;Jacobsen, Elin I.;Kalaitzakis, Evangelos
背景和目标：与他汀类药物相关的药物性肝损伤（DILI）数据有限：对瑞典药物不良反应咨询委员会1988-2010年收到的疑似他汀类药物不良反应报告进行分析。仅包括转氨酶>5 x正常上限（ULN）和/或碱性磷酸酶>2 x ULN的病例。结果：最常见的疑似ADR类型为DILI，124/217例（57%）。共有73/124例（59%）病例至少存在可能的关系，中位年龄64岁（57-73岁），55%为男性，而25/124例（20%）病例因肝功能检查轻度升高而被排除，26例病例因不太可能的关系和/或缺乏数据而被排除。1.2/100，000名使用者报告了他汀类药物相关DILI事件。阿托伐他汀与30/73例（41%）病例有关，辛伐他汀与28例（38%）病例有关，氟伐他汀与15%病例有关，其他病例有关。2例患者死于急性肝功能衰竭，1例接受肝移植，25例（34%）出现黄疸。3例患者再次使用相同的他汀类药物，产生相似的肝损伤模式。中位治疗持续时间为90天（30-120），阿托伐他汀为120天（39-248），辛伐他汀（NS）为75天（30-150）。阿托伐他汀组胆汁淤积性/混合性损伤较辛伐他汀组常见，17/30例（56%），7/28例（24%）（p = 0.018）。结论：与他汀类药物相关的特异质肝损伤罕见，但可能严重。恢复后，再次暴露时可再现类似的肝损伤模式。大多数患者在治疗开始后3-4个月出现肝损伤。阿托伐他汀主要与胆汁淤积性肝损伤相关，而辛伐他汀更常见于肝细胞损伤。(C)2011年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background & Aims: Limited data exist on drug-induced liver injury (DILI) associated with statins.Methods: Reports on adverse reactions suspected to be due to statins received by the Swedish Adverse Drug Reactions Advisory Committe 1988-2010 were analyzed. Only cases with >5 x upper limit of normal (ULN) in aminotransferases and/or alkaline phosphatase >2 x ULN were included.Results: The most common types of ADRs suspected were DILI in 124/217 (57%) cases. A total of 73/124 (59%) cases had at least possible relationship, median age 64 years (57-73), 55% males, whereas 25/124 cases (20%) were excluded due to mild elevations of liver tests and 26 due to unlikely relationship and/or lack of data. A statin-related DILI episode was reported in 1.2/100,000 users. Atorvastatin was implicated in 30/73 (41%) cases, simvastatin in 28 (38%), fluvastatin (15%), and others. Two patients died of acute liver failure, one underwent liver transplantation and 25 (34%) had jaundice. Three patients were rechallenged with the same statin producing similar patterns of liver injury. The median duration of therapy was 90 days (30-120), 120 (39-248) for atorvastatin, and 75 (30-150) for simvastatin (NS). Cholestatic/mixed injury was more common with atorvastatin, 17/30 (56%) than with simvastatin, 7/28 (24%) (p = 0.018).Conclusions: Idiosyncratic liver injury associated with statins is rare but can be severe. After recovery, a similar pattern of liver injury can be reproduced on re-exposure. Most patients experience liver injury 3-4 months after start of therapy. Atorvastatin is mostly associated with cholestatic liver injury whereas hepatocellular injury is more common with simvastatin. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.