【摘要】
背景与目的：他汀类药物相关的药物性肝损伤（DILI）方面的数据尚有限。方法：分析1988-2010年瑞典药品不良反应咨询委员会收到的疑是他汀类药物不良反应的报告，仅包括转氨酶> 5×正常值上限（ULN）和/或碱性磷酸酶>2×ULN的病例。结果：最常见疑是不良反应的类型是DILI，占57%（124/217）的病例。在这124例中，73例（59%）至少有可能的相关性，中位年龄64岁（57-73岁），55％为男性，而另外25例（25/124）由于肝功能检查轻度升高、26例（26/124）由于不大可能有相关性和/或缺乏数据被排除在外。他汀类药物相关的DILI发病为1.2/100000人次。在73例中，与阿托伐他汀相关的有30例（41%），辛伐他汀28例（38%），氟伐他汀11例（15%）及其它。2例患者死于急性肝功能衰竭，1例行肝移植，25例（34%）有黄疸。3例患者再次尝试相同的他汀类药物，产生了相似的肝损伤。中位治疗时间为90天（30-120天），其中阿托伐他汀120天（39-248天），辛伐他汀75天（30-150天）(NS)。胆汁淤积/混合性肝损伤在阿托伐他汀（17/30；56%）中较辛伐他汀（7/28；24%）更为多见（P = 0.018）。结论：他汀类药物相关的特异体质性肝损伤较为罕见，但可能是严重的。在恢复后，再次服用他汀类药物可发生类似的肝损伤类型。大多数患者肝损伤发生在他汀类药物治疗开始后的3-4个月。阿托伐他汀多与胆汁淤积性肝损伤相关，而辛伐他汀更多见肝细胞损伤。
江西省景德镇市第三人民医院消化内科 朱晓，杨力 摘译
本文首次发表于[J Hepatol,2012 ,56(2):374-280]
Hepatotoxicity associated with statins: reports of idiosyncratic liver injury post-marketing
Abstract
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×upper limit of normal (ULN) in aminotransferases and/or alkaline phosphatase >2×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 cholestaticliver injury whereas hepatocellular injury is more common with simvastatin.
