甲氨蝶呤治疗异位妊娠致肝损伤的临床特点和影响因素分析

目的分析甲氨蝶呤治疗异位妊娠致肝损伤的临床特点和影响因素,为临床安全用药提供参考。方法收集2018年1月1日—2020年5月31日使用甲氨蝶呤治疗的异位妊娠患者病历资料,回顾性分析患者肝损伤的临床特点,以及患者特征和药物因素对肝损伤的影响。结果共纳入320例患者,其中49例发生肝损伤,发生率为15.31%。临床分型均为肝细胞损伤型,RUCAM量表评分均在3分以上,38例(77.55%)≥6分。肝损伤多发生在停药后3 d内,严重程度主要为2级和3级。28例经保肝治疗后痊愈或好转,12例未经治疗自行痊愈或好转,9例未复查。分析显示,患者年龄(P=0.98)、体质量指数(P=0.19)、乙型肝炎表面抗原(HBsAg)是否阳性(P=0.13)和异位妊娠类型(P=0.78)均与肝损伤无关。不同治疗方案(P0.01)和合并使用致肝功能异常药物(P0.05)与肝损伤有关,预防性使用保肝药物未见对肝损伤有影响(P=0.92)。结论甲氨蝶呤引起的肝损伤发生较早,具有可逆性。5 d连续给药方案和合并使用致肝功能异常药物的患者更易引发肝损伤,建议加强监测肝功能,个体化选择治疗方案,避免不合理的联合用药。

Clinical characteristics and effect factors of liver injury induced by methotrexate for ectopic pregnancy

Objective To investigate the clinical characteristics and effect factors of liver injury induced by methotrexate after treatment for ectopic pregnancy, and to provide reference for clinical safe drug use. Methods The medical records of ectopic pregnancy patients treated with methotrexate from January 1, 2018 to May 31, 2020 were collected to retrospectively analyze the clinical characteristics of liver injury and the influence of patient characteristics and drug factors on liver injury. Results A total of 320 patients were enrolled, 49 of whom developed liver injury (15.31%), the clinical classification was hepatocyte injury type, RUCAM scale score were all above 3, and 38 cases (77.55%) were more than 6 points. Liver injury mostly occurred within 3 days after drug withdrawal, and the severity was grade 2 and 3. 28 cases were cured or improved after liver preservation treatment, 12 cases were cured or improved without treatment, and 9 cases were not reviewed. Analysis showed that age (P=0.98), body mass index (P=0.19), HBsAg positive (P=0.13), and ectopic pregnancy type (P=0.78) were not associated with liver injury. Different treatment regiments (P<0.01) and combined use of abnormal liver function drugs (P<0.05) were associated with liver injury, while preventive use of liver-protecting drugs had no effect on liver injury (P=0.92). Conclusion Methotrexate induced liver damage occurred earlier and was reversible. Patients with 5-day continuous administration regimen and combined use of drugs causing abnormal liver function are more likely to cause liver injury. It is suggested to strengthen monitoring of liver function and individual selection of treatment regimen to avoid unreasonable combination medication.