Motola Domenico, Vargiu Antonio, Leone Roberto, Cocci Alfredo, Salvo Francesco, Ros Barbara, Meneghelli Ilaria, Venegoni Mauro, Cutroneo Paola Maria, Vaccheri Alberto, Velo Gianpaolo, Montanaro Nicola
Department of Pharmacology and Interuniversity Research Centre for Pharmacoepidemiology, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
Eur J Clin Pharmacol. 2007 Jan;63(1):73-9. doi: 10.1007/s00228-006-0222-z. Epub 2006 Nov 22.
Adverse drug reactions (ADRs) can involve all tissues and organs. Liver injuries are considered among the most serious and are a cause for concern among physicians and patients. To assess the extent of drug-induced liver injuries in Italy we compared the number of cases of hepatic ADRs with reports of all other drug-related reactions present in the same database.
Spontaneous reports from six Italian Regions collected from January 1990 to May 2005 were analysed. Adverse reactions were classified according to WHO Adverse Reaction Terminology for causality assessment, and only those with "certain", "probable" or "possible" causality assessment were included. Association between drugs and hepatic ADRs was assessed using the case/non case method, calculating the ADR reporting odds ratio (ROR) as a measure of disproportionality.
On May 2005, the database contained 35,767 ADR reports, of which 11,829 were excluded because they were unclassifiable or unlikely in terms of causality assessment. Therefore, the analysis was carried out on 23,938 reports, of which 1,069 concerned hepatic ADRs (cases) and 22,869 concerned non-cases. The proportion of serious ADRs was about 40% in the overall database, and about 74% among cases. The drug classes with the highest number of cases were statins (ROR = 2.9, 95% CI 2.4-3.5), antiplatelet agents (ROR = 3.5; 95% CI 2.6-4.6), NSAIDs (ROR = 2.9; 95% CI 2.1-3.9) and macrolides (ROR = 1.7; 95% CI 1.2-2.3).
Hepatic adverse drug reactions remain a serious concern for several drugs widely used in clinical practice. Monitoring hepatic enzymes on a monthly basis for the first 6 months of treatment has been suggested for patients taking medications known to be hepatotoxic. A better knowledge of the epidemiology and mechanisms of hepatic ADRs may contribute to minimising their occurrence.
药物不良反应（ADR）可累及所有组织和器官。肝损伤被认为是最严重的不良反应之一，受到医生和患者的关注。为评估意大利药物性肝损伤的程度，我们将肝ADR病例数与同一数据库中所有其他药物相关反应报告进行了比较。
分析了1990年1月至2005年5月从意大利六个地区收集的自发报告。根据世界卫生组织不良反应术语对不良反应进行因果关系评估分类，仅纳入因果关系评估为“肯定”、“很可能”或“可能”的不良反应。采用病例/非病例方法评估药物与肝ADR之间的关联，计算ADR报告比值比（ROR）作为不成比例的衡量指标。
2005年5月，该数据库包含35767份ADR报告，其中11829份因无法分类或因果关系评估不太可能而被排除。因此，对23938份报告进行了分析，其中1069份涉及肝ADR（病例），22869份涉及非病例。严重ADR在整个数据库中的比例约为40%，在病例中约为74%。病例数最多的药物类别是他汀类药物（ROR = 2.9，95%CI 2.4 - 3.5）、抗血小板药物（ROR = 3.5；95%CI 2.6 - 4.6）、非甾体抗炎药（ROR = 2.9；95%CI 2.1 - 3.9）和大环内酯类药物（ROR = 1.7；95%CI 1.2 - 2.3）。
肝药物不良反应仍然是临床实践中广泛使用的几种药物的严重问题。建议对服用已知具有肝毒性药物的患者在治疗的前6个月每月监测肝酶。更好地了解肝ADR的流行病学和机制可能有助于减少其发生。
