Li Xiao-Xiao, Cheng Yin-Chu, Zhai Suo-di, Yao Peng, Zhan Si-Yan, Shi Lu-Wen
Department of Pharmacy, Peking University Third Hospital, Beijing, China.
Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Front Pharmacol. 2021 Mar 1;12:589091. doi: 10.3389/fphar.2021.589091. eCollection 2021.
To determine the risk of liver injury associated with the use of different intravenous lipid emulsions (LEs) in large populations in a real-world setting in China. A prescription sequence symmetry analysis was performed using data from 2015 Chinese Basic Health Insurance for Urban Employees. Patients newly prescribed both intravenous LEs and hepatic protectors within time windows of 7, 14, 28, 42, and 60 days of each other were included. The washout period was set to one month according to the waiting-time distribution. After adjusting prescribing time trends, we quantify the deviation from symmetry of patients initiating LEs first and those initiating hepatic protectors first, by calculating adjusted sequence ratios (ASRs) and relevant 95% confidence intervals. Analyses were further stratified by age, gender, and different generations of LEs developed. In total, 416, 997, 1,697, 2,072, and 2,342 patients filled their first prescriptions with both drugs within 7, 14, 28, 42, and 60 days, respectively. Significantly increased risks of liver injury were found across all time windows, and the strongest effect was observed in the first 2 weeks [ASR 6.97 (5.77-8.42) ∼ 7.87 (6.04-10.61)] in overall patients. In subgroup analyses, female gender, age more than 60 years, and soybean oil-based and alternative-LEs showed higher ASRs in almost all time windows. Specially, a lower risk for liver injury was observed in the first 14 days following FO-LEs administration (ASR, 3.42; 95% CI, 0.81-14.47), but the risk started to rise in longer time windows. A strong association was found between LEs use and liver injury through prescription sequence symmetry analysis in a real-world setting, which aligns with trial evidence and clinical experience. Differences revealed in the risks of liver injury among various LEs need further evaluation.
在中国的实际环境中，确定在大量人群中使用不同静脉注射脂肪乳剂（LEs）与肝损伤风险之间的关系。利用2015年中国城镇职工基本医疗保险的数据进行了处方序列对称性分析。纳入在彼此7天、14天、28天、42天和60天的时间窗口内新开具静脉注射LEs和肝保护剂的患者。根据等待时间分布将洗脱期设定为1个月。在调整处方时间趋势后，我们通过计算调整后的序列比（ASR）和相关的95%置信区间，量化首先开始使用LEs的患者和首先开始使用肝保护剂的患者与对称性的偏差。分析进一步按年龄、性别和不同代次的LEs进行分层。总共分别有416、997、1697、2072和2342名患者在7天、14天、28天、42天和60天内首次开具这两种药物的处方。在所有时间窗口中均发现肝损伤风险显著增加，在总体患者中，在前2周观察到最强的效应[ASR 6.97（5.77 - 8.42）至7.87（6.04 - 10.61）]。在亚组分析中，女性、60岁以上的年龄以及基于大豆油的和替代LEs在几乎所有时间窗口中显示出较高的ASR。特别地，在给予FO - LEs后的前14天观察到较低的肝损伤风险（ASR，3.42；95% CI，0.81 - 14.47），但在更长的时间窗口中风险开始上升。通过在实际环境中的处方序列对称性分析发现LEs使用与肝损伤之间存在强烈关联，这与试验证据和临床经验一致。不同LEs之间肝损伤风险的差异需要进一步评估。
