Risk of acute and serious liver injury associated to nimesulide and other NSAIDs: data from drug-induced liver injury case-control study in Italy
Risk of acute and serious liver injury associated to nimesulide and other NSAIDs: data from drug-induced liver injury case-control study in Italy
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DOI：
10.1111/bcp.12938
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发表时间：
2016-07-01
影响因子：
3.4
通讯作者：
Leone, Roberto
中科院分区：
文献类型：
--
作者：
Donati, Monia;Conforti, Anita;Leone, Roberto
药物性肝损伤是最严重的药物不良反应之一，也是限制适应症或停药的最常见原因。一些非甾体类抗炎药（NSAIDs）因严重的肝毒性而退出市场。我们估计急性和严重肝损伤的风险与尼美舒利和其他非甾体抗炎药的使用有关，使用的患病率大于或等于5%。方法2010年10月至2014年1月在意大利9家医院开展多中心病例对照研究。病例为成人，诊断为急性肝损伤。对照组表现为急性临床疾病，与慢性疾病无关，不涉及肝脏。校正优势比（ORs）和95%可信区间（CI）最初通过双变量分析和多变量分析计算。结果纳入179例病例，对照1770例。所有非甾体抗炎药相关急性严重肝损伤的校正OR为1.69,95% CI为1.21-2.37。30例暴露于尼美舒利（调整OR 2.10, 95% CI 1.28-3.47）；根据暴露时间长短（OR: 12.55, 95% CI 1.73-90.88）和较高剂量（OR: 10.69, 95% CI 4.02-28.44），风险增加。布洛芬在推荐剂量（OR 1.92, 95% CI 1.13-3.26）和更高剂量（OR 3.73, 95% CI 1.11-12.46）和酮洛芬>= 150 mg （OR 4.65, 95% CI 1.33-10.00）下的肝毒性风险也增加。结论在所有非甾体抗炎药中，尼美舒利与较高的肝毒性风险相关，布洛芬和大剂量酮洛芬也与肝毒性风险适度增加相关。
AIMDrug-induced liver injury is one of the most serious adverse drug reactions and the most frequent reason for restriction of indications or withdrawal of drugs. Some nonsteroidal anti-inflammatory drugs (NSAIDs) were withdrawn from the market because of serious hepatotoxicity. We estimated the risk of acute and serious liver injury associated with the use of nimesulide and other NSAIDs, with a prevalence of use greater than or equal to 5%.METHODSThis is a multicentre case-control study carried out in nine Italian hospitals from October 2010 to January 2014. Cases were adults, with a diagnosis of acute liver injury. Controls presented acute clinical disorders not related to chronic conditions, not involving the liver. Adjusted odds ratio (ORs) with 95% confidence interval (CI) were calculated initially with a bivariate and then multivariate analysis.RESULTSWe included 179 cases matched to 1770 controls. Adjusted OR for acute serious liver injury associated with all NSAIDs was 1.69, 95% CI 1.21-2.37. Thirty cases were exposed to nimesulide (adjusted OR 2.10, 95% CI 1.28-3.47); the risk increased according to the length of exposure (OR > 30 days: 12.55, 95% CI 1.73-90.88) and to higher doses (OR 10.69, 95% CI 4.02-28.44). Risk of hepatotoxicity was increased also for ibuprofen, used both at recommended dosages (OR 1.92, 95% CI 1.13-3.26) and at higher doses (OR 3.73, 95% CI 1.11-12.46) and for ketoprofen >= 150 mg (OR 4.65, 95% CI 1.33-10.00).CONCLUSIONAmong all NSAIDs, nimesulide is associated with the higher risk, ibuprofen and high doses of ketoprofen are also associated with a modestly increased risk of hepatotoxicity.