儿童抗结核药物性肝损伤状况及相关影响因素分析

doi:10.19982/j.issn.1000-6621.20220290

摘要/Abstract

摘要：

目的: 分析儿童抗结核药物性肝损伤(drug-induced liver injury during anti-tuberculosis treatment,ATB-DILI)状况及相关影响因素。方法: 采用回顾性研究方法,收集2018年6月至2022年6月南华大学衡阳医学院附属长沙中心医院确诊为结核病且符合纳入标准的200例住院或门诊儿童患者临床资料。所有患儿均全疗程使用护肝药物,其中,发生肝损伤患儿52例,ATB-DILI发病率为26.0%。分析结核病患儿发生ATB-DILI的临床表现、严重程度、病理损害、发生时间分布及相关影响因素。结果: 52例肝损伤患儿中,20例(38.5%)无明显症状仅肝功能指标异常,32例(61.5%)厌食,29例(55.8%)呕吐,3例(5.8%)黄疸,均加用护肝药及对症处理后好转;51例为 1级(轻度)ATB-DILI,1例为2级(中度),无3~5级肝损伤患者;均为肝细胞损伤型患者。在开始抗结核治疗2周内有29例(55.8%)发生ATB-DILI,第3~8周有8例(15.4%),第9~12周有5例(9.6%),第13~16周有7例(13.5%),第16~24周有3例(5.7%)。多因素logistic回归分析显示,体质量指数低于18.5[OR(95%CI)=2.340(1.104~4.959)]、血清前白蛋白低于200mg/L[OR(95%CI)=2.337(1.093~4.997)]和血红蛋白低于120g/L[P=0.016,OR(95%CI)=2.403(1.176~4.908)]均是儿童结核病患者发生ATB-DILI的独立危险因素。结论: 儿童结核病在抗结核治疗全疗程中使用护肝药物的基础上,ATB-DILI的发生率仍不低,但其临床表现、严重程度、病理损害明显降低。临床医师应重点关注治疗2周内体质量指数、血清前白蛋白和血红蛋白降低的患儿发生ATB-DILI的风险。

关键词: 儿童, 抗结核药, 药物性肝损伤, 因素分析, 统计学

Abstract:

Objective: To analyze the status and related influencing factors of anti-tuberculosis drug-induced liver injury (ATB-DILI) in children. Methods: A retrospective study was conducted to enroll 200 hospitalized or outpatient children who were diagnosed with tuberculosis and met the enrollment criteria from June 2018 to June 2022 in the Changsha Central Hospital Affiliated Hospital, Hengyang Medical School, University of South China. All children used hepatoprotective drugs throug the full course. Among them, 52 patients developed ATB-DILI, with an incidence rate of 26.0%. We analyzed the clinical manifestations, severity, pathological damage, onset time, and related influencing factors of ATB-DILI in those children. Results: Among the 52 children who developed liver injury, 20 cases (38.5%) had no obvious symptoms but only abnormal liver function test results, 32 cases (61.5%) were anorexic, 29 cases (55.8%) vomited, and 3 cases (5.8%) showed jaundice, all patients were recovering with liver-protecting drugs and symptomatic treatment; 51 cases had grade 1 (mild) ATB-DILI, 1 case got grade 2 (moderate), and there were no patients with grade 3-5 liver injury. Liver injury type were hepatocellular injury for all patients. ATB-DILI occurred in 29 cases (55.8%) within 2 weeks after anti-tuberculosis treatment started, 8 cases (15.4%) within 3-8 weeks, 5 cases (9.6%) within 9-12 weeks, 7 cases (13.5%) within 13-16 weeks, and 3 cases (5.7%) within 16-24 weeks. Multifactorial logistic regression analysis showed that body mass index <18.5 (OR (95%CI)=2.340 (1.104-4.959)), serum pre-albumin <200 mg/L (OR (95%CI)=2.337 (1.093-4.997)) and hemoglobin <120 g/L (OR (95%CI)=2.403 (1.176-4.908)) were independent risk factors for the development of ATB-DILI in children with tuberculosis. Conclusion: The incidence of ATB-DILI in tuberculosis children who used hepatoprotective drugs through the full course of anti-tuberculosis treatment is still not low, but its clinical manifestations, severity, and pathological damage are significantly reduced. Clinicians should pay attention to the risk of ATB-DILI in pediatric patients with tuberculosis whose body mass index, serum prealbumin, and hemoglobin are below normal values within 2 weeks after anti-tuberculosis treatment initiated.

Key words: Child, Antitubercular agents, Drug-induced liver injury, Factor analysis, statistical

中图分类号:

陈芳, 张小佛, 周海依, 张锋, 王曼知. 儿童抗结核药物性肝损伤状况及相关影响因素分析[J]. 中国防痨杂志, 2023, 45(1): 45-51. doi: 10.19982/j.issn.1000-6621.20220290

Chen Fang, Zhang Xiaofo, Zhou Haiyi, Zhang Feng, Wang Manzhi. Analysis of status and influencing factors associated with anti-tuberculosis drug-related liver injury in children[J]. Chinese Journal of Antituberculosis, 2023, 45(1): 45-51. doi: 10.19982/j.issn.1000-6621.20220290

图/表 3

表1

表2

表3

儿童结核病患者发生ATB-DILI的多因素logistic回归分析

变量	β值	s $x ˉ$ 值	Wald χ²值	P值	OR(95%CI)值
体质量指数	0.850	0.383	4.922	0.027	2.340(1.104~4.959)
前白蛋白	0.849	0.388	4.790	0.029	2.337(1.093~4.997)
血红蛋白	0.877	0.364	5.784	0.016	2.403(1.176~4.908)
白蛋白	0.409	0.367	1.245	0.264	1.506(0.734~3.089)

表3

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影响因素	非肝损伤组(148例)	肝损伤组(52例)	检验值	P值
性别			χ²=0.001	0.979
男性	68(45.9)	24(46.2)
女性	80(54.1)	28(53.8)
年龄组(岁)			χ²=3.033	0.387
≤3	44(29.7)	11(21.2)
4~5	15(10.1)	5(9.6)
6~10	25(16.9)	14(26.9)
11~18	64(43.3)	22(42.3)
影响因素	非肝损伤组(148例)	肝损伤组(52例)	检验值	P值
体质量指数			χ²=11.931	0.001
<18.5	67(45.3)	38(73.1)
≥18.5	81(54.7)	14(26.9)
病原学阳性			χ²=2.434	0.119
是	53(35.8)	25(48.1)
否	95(64.2)	27(51.9)
多部位结核			χ²=2.125	0.145
是	68(45.9)	30(57.7)
否	80(54.1)	22(42.3)
血红蛋白(g/L)			χ²=10.706	0.001
<120	40(27.0)	27(51.9)
≥120	108(73.0)	25(48.1)
前白蛋白(mg/L)			χ²=11.357	0.001
<200	71(48.0)	39(75.0)
≥200	77(52.0)	13(25.0)
白蛋白(g/L)			χ²=5.881	0.015
<42	65(43.9)	33(63.5)
≥42	83(56.1)	19(36.5)
血肌酐(μmol/L)			χ²=0.086	0.769
<33	86(58.1)	29(55.8)
≥33	62(41.9)	23(44.2)
血尿酸(μmol/L)			χ²=2.016	0.156
≤357	68(45.9)	18(34.6)
>357	80(54.1)	34(65.4)
血尿素氮(mmol/L)			χ²=0.241	0.887
<2.5	11(7.4)	5(9.6)
2.5~6.5	134(90.6)	46(88.5)
>6.5	3(2.0)	1(1.9)
免疫球蛋白E(IU/ml)			χ²=0.059	0.807
≤358	130(87.8)	45(86.5)
>358	18(12.2)	7(13.5)