头孢曲松引起成年患者药物性肝脏损害分析

Analysis of drug-induced liver injury in adult patients caused by ceftriaxone

目的:分析成年患者应用头孢曲松过程中,发生肝脏损害(drug-induced liver injury,DILI)的危险因素。方法:回顾选取2015年1月至2016年12月于复旦大学附属中山医院使用头孢曲松注射液的成年患者384例。通过医院信息管理系统收集患者资料,包括基本信息、感染诊断、感染部位及其他合并症;观察指标主要包括用药前后肝功能指标以及合并用药情况。依据头孢曲松使用剂量分为低剂量(≤2g/d)组和高剂量(>2g/d)组,比较两组患者DILI的发生率。将患者分为肝损害组和肝未损害组,分析两组头孢曲松应用情况。结果:高剂量组为66例(17.2%),低剂量组为318例(82.8%)。384例患者中,12例(3.1%)在使用头孢曲松期间发生DILI,高剂量组发生率高于低剂量组(13.6%vs 0.9%;OR=16.58,95%CI 4.35～63.11,P<0.001);384例患者中,44例(11.4%)发生轻度肝脏损害,高剂量组发生率高于低剂量组(25.8%vs 8.5%;OR=3.74,95%CI 1.90～7.37,P<0.001)。单因素分析结果显示,应用高剂量头孢曲松(>2g/d)是发生DILI的危险因素(OR=16.58,95%CI 4.36～63.11,P<0.001)。结论:应用高剂量头孢曲松(>2g/d)的成人患者发生DILI的风险较大,是成人患者发生DILI的危险因素。

Objective：To identify clinical risk factors for drug-induced liver injury in adult patients when using ceftriaxone.Methods：A total of 384 hospitalized adult patients receiving ceftriaxone treatment were selected in the Zhongshan Hospital,Fudan University from January 2015 to December 2016.The baseline characteristics,diagnoses and sites of infection,comorbidities,concomitant medications,and laboratory data indicating liver function before and after treatment,were recorded.The patients were divided into the high-dose（2 g/d）ceftriaxone group and the low-dose（≤2 g/d）ceftriaxone group,and the incidence of drug-induced liver injury between the two groups was compared.Furthermore,patients were divided into liver-injury group and non-liver-injury group,and the applications of ceftriaxone were analyzed.Results：Sixty-six（17.2%）cases received high-dose ceftriaxone,and 318（82.8%）cases received low-dose ceftriaxone.Among the 384 cases,12（3.1%）cases experienced liver injury during the ceftriaxone treatment,the incidence of liver injury in the high-dose ceftriaxone group was higher than that in the low-dose group（13.6%vs 0.9%;OR=16.58,95%CI 4.35-63.11,P〈0.001）;44（11.4%）cases experienced mild liver injury,and the incidence of mild liver injury in the high-dose group was also higher than that in the low-dose group（25.8%vs 8.5%;OR=3.74,95% CI 1.90-7.37,P〈0.001）.Univariate analysis revealed that high-dose ceftriaxone（2 g/d）was an risk factor for drug-induced liver injury（OR=16.58,95% CI 4.35-63.11,P〈0.001）.Conclusions：High-dose（2 g/d）ceftriaxone was associated with a significantly higher incidence of drug-induced liver injury,and might be a risk factor for drug-induced liver injury in adult patients.