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妊娠女性药物相关肝损伤风险的识别及分析
DOI: 10.3969/j.issn.1001-5256.2022.08.021
利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明：母光頔、李佳怡承担数据分析及论文撰写；高云娟、赵旭承担数据采集分析; 王伽伯、柏兆方、肖小河对本文进行了方法学指导及论文修改；郭玉明承担方案设计与论文撰写。
Identification and analysis of the risk of liver-related adverse drug reaction in pregnant women
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摘要:
目的 通过对妊娠女性药物相关肝损伤不良反应(ADR)特征识别与分析，警示其潜在用药风险。 方法 收集中草药肝损伤云系统(hilicloud.net)中2012年1月1日—2016年12月31日妊娠女性药物相关肝损伤ADR报告进行回顾性研究，分析其主要临床特征及用药规律，并采用报告比值比(ROR)对相关药物进行相对风险分析。计量资料组间比较采用t检验。 结果 妊娠女性药物相关肝损伤报告的高频药物有甲氨蝶呤、米非司酮、利托君等，主要用于终止异位妊娠及葡萄胎等疾病的治疗。药物相关肝损伤相对风险分析发现，妊娠女性使用甲氨蝶呤(ROR=37.52，95%CI：31.35~44.89)、黄体酮(ROR=7.33，95%CI：2.75~19.59)、地屈孕酮(ROR=6.58，95%CI：2.20~19.69)与肝损伤风险相关性较强，其中妊娠女性(ROR=37.52，95%CI：31.35~44.89)使用甲氨蝶呤比非妊娠女性(ROR=1.71，95%CI：1.47~4.36)使用发生肝损伤的风险相关性强。 结论 应重视甲氨蝶呤、黄体酮等药物在妊娠女性人群中发生肝损伤的潜在风险，避免严重不良反应的发生。 -
关键词:
- 妊娠 /
- 化学性与药物性肝损伤 /
- 药物相关性副作用和不良反应
Abstract:Objective To investigate the potential medication risk by identifying and analyzing the features of liver-related adverse drug reaction (ADR) in pregnant women. Methods A retrospective study was performed for the reports on liver-related ADR in pregnant women from January 1, 2012 to December 31, 2016 in HILI Cloud (hilicloud.net). Main clinical features and medication rules were analyzed, and reporting odds ratio (ROR) was used to analyze the relative risk of related drugs. Results Methotrexate, mifepristone, and ritodrine were the high-frequency drugs reported for liver-related ADR in pregnant women and were mainly used for termination of ectopic pregnancy and treatment of hydatidiform mole. The relative risk analysis of liver-related ADR showed that in pregnant women, the use of methotrexate (ROR=37.52, 95% confidence interval [CI]=31.35-44.89), progesterone (ROR=7.33, 95%CI: 2.75-19.59), and dydrogesterone (ROR=6.58, 95%CI: 2.20-19.69) was strongly associated with the risk of liver injury, and the association of methotrexate with the risk of liver injury in pregnant women was significantly stronger than that in non-pregnant women (ROR=1.71, 95%CI: 1.47-4.36). Conclusion The potential risk of liver injury should be taken seriously in pregnant women using the drugs such as methotrexate and progesterone, so as to avoid serious adverse reactions. -
图 2 不同药物肝损伤相对风险分析
注：仅分析肝损伤ADR报告频次≥3(a≥3)的药物。
Figure 2. Analysis of the relative risk of drug-related liver injury with different drugs
图 3 妊娠女性与非妊娠女性使用甲氨蝶呤的年龄分布及疾病
Figure 3. Age distribution and disease of methotrexate use in pregnant and non-pregnant women
表 1 药物相关肝损伤ADR报告频数排名前十的药物
Table 1. Reporting frequency of liver-related ADR for Top 10
药物 报告数(例) 占比(%) 药物 报告数(例) 占比(%) 甲氨蝶呤 871 78.33 地屈孕酮 9 0.81 米非司酮 135 12.14 5-氟尿嘧啶 7 0.63 利托君 13 1.17 亚叶酸钙 5 0.45 黄体酮 12 1.08 放线菌素D 5 0.45 肝素 11 0.99 依托泊苷 4 0.36 
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