儿童与成年患者药物性肝损伤临床特征比较

Comparison of clinical characteristics between the children and adults patients with drug-induced liver injury

目的：分析比较儿童与成年患者药物性肝损伤（ DILI）的临床特征方法以“药物性肝损伤”为检索词，检索2002年2月至2011年6月首都医科大学附属北京佑安医院病案管理中心的全部病历，将患者中≤14岁者纳入儿童组，≥15岁者纳入成年组。收集2组患者的病历资料进行回顾性分析，主要分析指标为用药情况、临床表现以及DILI的临床和病理分型。结果导致儿童组DILI的主要药物为抗菌药（13例，42%）、中药（9例，29%）和解热镇痛药（6例，19%）。导致成年组DILI的主要药物为中药（79例，69%）、解热镇痛药（12例，11%）和抗菌药（8例，7%）。儿童组26例（84%）、成年组114例（100%）分别在用药3-90 d[平均（18±15）d]和5-90 d[平均（30±20）d]后出现乏力、食欲减退、厌油、恶心、呕吐和尿液变黄，部分患者出现发热、皮疹及嗜酸粒细胞计数升高。实验室检查显示，2组患者血清丙氨酸转氨酶（ ALT）、天冬氨酸转氨酶（ AST）及谷氨酰转肽酶（GGT）水平差异无统计学意义，但儿童组碱性磷酸酶（ALP）水平明显高于高于成年组（P〈0.05）。儿童组31例患者中混合型肝损伤15例（48.4%），肝细胞型和胆汁淤积型各8例（各25.8%）；成年组114例患者中肝细胞型肝损伤69例（60.5%），混合型26例（22.8%），胆汁淤积型19例（16.7%）。儿童组混合型肝损伤占比明显高于而肝细胞型肝损伤占比明显低于成年组（均 P 〈0.01）。出现DILI症状后，2组患者均立即停用有关药物，并给予保肝降酶及对症治疗。成年组所有患者与儿童组27例患儿好转出院，儿童组原发疾病恶化2例，因肝功能衰竭自行出院和死亡各1例。结论儿童和成人DILI的主要致病药物不同，前者以抗菌药为主，后者以中药为主。儿童DILI分型以混合型为主，成人则以肝细胞型为主。儿童使用抗菌药、成人使用中药时尤应警惕DILI的发生。

Objective To compare the clinical characteristics between the children and adults patients with drug-induced liver injury（ DILI）. Methods ＂Drug-induced liver injury＂ was selected as the key word and all the medical records in Beijing You＆#39;an Hospital Medical Records Management Center from February 2002 to June 2011 were collected. The patients who were ≤14 years were enrolled into the child group. The patients who were ≥15 years were enrolled into the adult group. The medical records of patients in the two groups were collected and analyzed retrospectively. The main analysis parameters included use of medication,clinical manifestation,and clinical pathological classification of DILI. Results The main drugs which can cause DILI in child group were antibacterial drugs（ 13 cases,42%）,traditional Chinese medicines（9 cases,29%）,and antipyretic analgesics（6 cases,19%）. The main drugs which can cause DILI in the adult group were traditional Chinese medicines（ 79 cases,69%）,antipyretic analgesics（12 cases,11%）,and antibacterial drugs（8 cases,7%）. Twenty-six patients（84%）in the child group and 114 patients（100%）in the adult group developed weak,loss of appetite,aversion to fats, nausea,vomiting and yellow urine 3 to 90 days[mean（18 ± 15）days]and 5 to 90 days[mean（30 ± 20） days] after drug admission, respectively. Part of patients developed fever, erythema and increased eosinophils. There were no significant differences in the levels of serum alanine transaminase（ ALT ）, aspartate aminotransferase（ AST）,and glutamyltranspetidase between the two groups. But the level of serum＆amp;nbsp;alkaline phosphatase（ALP）in the child group was higher than that in the adult group（P〈0. 05）. The number of mixed DILI,hepatocellular DILI and cholestasis DILI were 15（48. 4%）,8（25%）and 8 （25%）cases in 31 patients in the child group,respectively. The number of hepatocellular DILI,mixed DILI,and cholestasis DILI were 69（60. 5%）,26（22. 8%）and 19（16. 7%）cases in 114 patients in the adult group,respectively. The proportion of mixed DILI in child group was significantly higher than that in the adult group（P〈0. 01）. The proportion of hepatocellular DILI in the child group was significantly lower than that in the adult group（P〈0. 01）. The drugs were withdrawn immediately after the symptoms of DILI appeared in the patient in the two groups. All the patients in the adult group and 27 children in the child group were improved and discharged. There were 2 cases with depravation of primary diseases,1 case discharged himself and 1 case died due to hepatic failure in the child group Conclusions The main drugs causing DILI are different in children and adult;in children,antibacterial drugs ,while in adults traditional Chinese medicine mainly. The mainly liver injury type in children is mixed DILI. The mainly liver injury type in adults is hepatocellular DILI. It should be vigilant towards DILI when the child or adult treated with antibiotics or traditional Chinese medicine.