氟比洛芬(酯)引起的肝损伤病例报告及文献评价

Review on Cases and Literature of Flurbiprofen(Axetil)-induced Liver Damage

目的评价临床应用氟比洛芬(酯)与患者肝损伤的关联性。方法以氟比洛芬(酯)为主题词,以药品不良反应(ADR)、肝毒性、肝损伤、转氨酶及高胆红素为检索词,全面检索CNKI、万方医学数据库、VIP、Pubmed、Medline、Cochrane Central数据库,收集1980年1月至2017年11月国内外发表的文献;阅读并筛选文献,将有关ADR报道,药物安全性研究报道纳入研究;设计数据记录表,提取基本信息、方法特征、干预措施等信息;采用描述性评价方法判断氟比洛芬(酯)引起肝损伤的发生概率、程度及类型。结果根据纳入标准共筛选出8篇有效文献,3篇随机试验,1篇处方统计,1篇病例统计,3篇单个病例数据研究;分析3篇随机试验,共涉及1 210名患者,约1%的患者出现肝功能异常,初步判断氟比洛芬(酯)致肝损伤较常见;6篇文献记录了患者肝损伤的异常指标,5篇文献指出转氨酶异常,2篇文献指出碱性磷酸酶异常,均未提及胆红素指标的变化,判断该药主要引起轻度肝损伤并以转氨酶异常为主。结论笔者认为氟比洛芬(酯)致肝损伤较常见,以轻度及转氨酶异常为主。但是目前所筛文献数量有限,质量较差,后期将通过对笔者所在医院更多的临床案例进行统计分析,进一步说明氟比洛芬(酯)与患者肝损伤的关联性。

Objective To evaluate the association between flurbiprofen axetil and liver damage in clinical use. Methods Taking flurbiprofen（axetil） as subject terms, and adverse drug reactions, hepatotoxicity, hepatic damage, transaminases and hyperbilirubin as search term, the authors collected literatures from CNKI, WANFANG Medical Database, VIP Database, Pubmed, Medline and Cochrane CENTRAL Database published at home and abroad from January 1980 to November 2017. The literatures were read and screened for the ADR case reports and drug safety research reports into the study. Data record sheets was designed and the basic information, method feature and intervention were picked up and recorded. Using descriptive research method, the authors evaluated the probability, extent and type of liver damage caused by flurbiprofen（axetil）. Results There were 3 randomized trials studies, 1 prescription statistic study, 1 case statistic study and 3 individual case data studies in 8 papers screened. By analyzing 1 210 patients in 3 randomized trials studies, the authors found that about 1% of patients have abnormal liver function. Then they concluded that flurbiprofen（axetil）-induced liver damage was not an uncommon adverse effect. 6 literatures recorded abnormal indicators of liver function without the changes of the bilirubin index. 5 of them indicated abnormal transaminase index and 2 of them indicated abnormal alkaline phosphatase index. The degree of liver damage is judged to be mild and abnormal transaminase to be the main type of liver injury. Conclusion The authors think that flurbiprofen（axetil）-induced liver damage is a common adverse effect and the degree of injury is mainly mild and abnormal transaminase is judged as the main type of liver injury. Considering the limited number and poor quality of current literatures, the relationship between flurbiprofen（axetil） and liver damage needs further study with more clinical statistical analysis in the authors＇ hospitals.