肺结核合并糖尿病患者药物性肝损伤影响因素分析

doi:10.19982/j.issn.1000-6621.20210545

摘要/Abstract

摘要：

目的: 分析肺结核合并糖尿病患者(PTB-DM)发生抗结核药物性肝损伤(anti-tuberculosis drug-induced liver injury,ATB-DILI)的影响因素。方法: 采用前瞻性队列研究的方法,连续纳入2017年10月至2019年3月青岛市中心医院北部院区符合入组标准的458例住院PTB-DM患者作为研究对象。通过自行设计的结构式调查问卷收集研究对象治疗前的年龄、性别、婚姻状况、文化水平、职业、膳食、吸烟、饮酒、体力活动水平、结核病临床症状、体质量指数、血生化指标、血常规指标、血糖控制水平、保肝药物使用及种类情况等信息;随访8个月后采用多因素Cox比例风险回归模型分析研究对象发生ATB-DILI的情况及其影响因素。结果: 458例PTB-DM患者中,53例发生ATB-DILI,发生率为11.6%。在调整了吸烟、体力活动、保肝药物使用和贫血等混杂因素后,发现血糖控制不良[HR(95%CI)=2.787(1.2566.183)]、饮酒[HR(95%CI)=2.159(1.097~4.251)]、消瘦(体质量指数<18.5)[HR(95%CI)=2.808(1.391~5.670)]、膳食多样性不足[HR(95%CI)=3.199(1.372~7.459)]是PTB-DM患者发生ATB-DILI的危险因素。结论: PTB-DM患者抗结核治疗后易发生ATB-DILI,尤其饮酒、消瘦和膳食多样性不足者,发生ATB-DILI的风险更高。

关键词: 结核,肺, 糖尿病, 药物性肝损伤, 共病现象, 因素分析,统计学

Abstract:

Objective: To analyze the influencing factors of anti-tuberculosis drug-induced liver injury (ATB-DILI) in patients with pulmonary tuberculosis complicated with diabetes mellitus (PTB-DM). Methods: A prospective cohort study was conducted to continuously enroll 458 inpatients with PTB-DM who met the enrollment criteria from October 2017 to March 2019 in the North Branch of Qingdao Central Hospital. Before their treatment, we collected information of age, gender, marital status, education level, occupation, diet, smoking, drinking, physical activity level, clinical symptoms of tuberculosis, body mass index, blood biochemical index, blood routine index, blood glucose control level,usage and types of liver protection drugs through a self-designed structured questionnaire; after following-up for eight months, a multivariate Cox proportional hazard regression was done to analyze the occurrence of ATB-DILI and its influencing factors. Results: Among 458 PTB-DM patients,53 patients developed ATB-DILI, with an incidence rate of 11.6%. After adjusting for confounding factors such as smoking, physical activity, liver protection drugs and anemia, it was found that poor glycemic control (HR (95%CI)=2.787 (1.256-6.183)), drinking (HR (95%CI)=2.159 (1.097-4.251)), low weight (body mass index <18.5) (HR (95%CI)=2.808 (1.391-5.670)) and insufficient dietary diversity (HR (95%CI)=3.199 (1.372-7.459)) were risk factors for ATB-DILI in PTB-DM patients. Conclusion: Patients with PTB-DM were prone to develop ATB-DILI after anti-tuberculosis treatment, especially for those who had drinking habits, with low weight and inadequate dietary diversity, they were associated with a higher risk of ATB-DILI.

Key words: Tuberculosis,pulmonary, Diabetes mellitus, Drug-induced liver injury, Comorbidity, Factor analysis,statistical

中图分类号:

张洋婷, 卢学昭, 李晓娜, 仲昭亿, 王娜, 蔡静, 马爱国, 刘玉峰, 汪求真. 肺结核合并糖尿病患者药物性肝损伤影响因素分析[J]. 中国防痨杂志, 2022, 44(1): 64-70. doi: 10.19982/j.issn.1000-6621.20210545

ZHANG Yang-ting, LU Xue-zhao, LI Xiao-na, ZHONG Zhao-yi, WANG Na, CAI Jing, MA Ai-guo, LIU Yu-feng, WANG Qiu-zhen. Study on influencing factors of anti-tuberculosis drug-induced liver injury in pulmonary tuberculosis patients complicated with diabetes mellitus[J]. Chinese Journal of Antituberculosis, 2022, 44(1): 64-70. doi: 10.19982/j.issn.1000-6621.20210545

图/表 5

表1

表2

不同临床指标在发生肝损伤与未发生肝损伤的肺结核合并糖尿病患者中的分布情况

临床指标	肝损伤组(53例)	无肝损伤组(405例)	统计检验值	P值
结核病特征性表现[例(发生率,%)]
咳嗽	48(90.6)	365(90.6)	χ²=0.000	1.000
咳痰	45(84.9)	325(80.6)	χ²=0.556	0.456
咯血	8(15.1)	53(13.2)	χ²=0.153	0.696
发热	19(35.8)	141(35.0)	χ²=0.015	0.902
乏力	22(41.5)	177(43.9)	χ²=0.111	0.739
盗汗	17(32.1)	120(29.8)	χ²=0.118	0.731
胸痛	12(22.6)	69(17.1)	χ²=0.977	0.323
食欲减退	10(18.9)	51(12.7)	χ²=1.560	0.212
胸闷	22(41.5)	184(45.7)	χ²=0.325	0.568
血脂异常[例(发生率,%)]
高甘油三酯血症	3(5.7)	28(6.9)	χ²=0.117	0.733
高胆固醇血症	1(1.9)	21(5.2)	χ²=1.115	0.291
混合型高脂血症	3(5.7)	9(2.2)	χ²=2.171	0.141
低高密度脂蛋白血症	24(45.3)	115(28.4)	χ²=6.323	0.012
总蛋白(g/L, $x ¯$ ±s)	66.00±7.69	66.71±7.25	t=0.454	0.524
白蛋白(g/L, $x ¯$ ±s)	36.81±5.45	39.78±12.39	t=3.144	0.099
低蛋白血症[例(发生率,%)]	6(11.3)	25(6.2)	χ²=1.968	0.161
贫血[例(发生率,%)]	20(37.7)	85(21.0)	χ²=7.440	0.006
空腹血糖^a(mmol/L, $x ¯$ ±s)	12.36±4.67	9.45±3.52	t=-4.184	<0.001
血糖控制不良^a[例(发生率,%)]	40(83.3)	260(68.2)	χ²=4.617	0.032

表2

表3

发生与未发生肝损伤的肺结核合并糖尿病患者膳食多样化评分情况

膳食多样化	肝损伤(53例)	无肝损伤(305例)^a	统计检验值	P值
膳食多样化评分(分, $x ¯$ ±s)	6.49±2.08	7.47±1.64	t=3.812	<0.001
膳食多样性[例(构成比,%)]			χ²=8.698	0.013
不足	7(13.2)	16(5.2)
适中	16(30.2)	61(20.0)
充足	30(56.6)	228(74.8)

表3

表4

表5

肺结核合并糖尿病患者发生抗结核药物性肝损伤影响因素的Cox比例风险回归分析

变量	β值	s $x ¯$ 值	Wald χ²值	P值	HR(95%CI)值
血糖控制不良	1.025	0.407	6.355	0.012	2.787(1.256~6.183)
吸烟	-0.432	0.344	1.570	0.210	0.649(0.331~1.276)
饮酒	0.770	0.346	4.959	0.026	2.159(1.097~4.251)
中/重体力活动	-0.455	0.344	1.743	0.187	0.635(0.323~1.246)
使用保肝药情况	—0.432	0.405	1.140	0.286	0.649(0.294~1.435)
消瘦(体质量指数<18.5)	1.032	0.359	8.294	0.004	2.808(1.391~5.670)
贫血	0.420	0.305	1.902	0.168	1.522(0.838~2.765)
膳食多样性不足	1.163	0.432	7.244	0.007	3.199(1.372~7.459)

表5

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基本特征	肝损伤组(53例)	无肝损伤组(405例)	χ²值	P值
年龄(岁)			0.238	0.626
≥60	15(28.3)	128(31.6)
<60	38(71.7)	277(68.4)
性别			1.194	0.274
男性	43(81.1)	351(86.7)
女性	10(18.9)	54(13.3)
婚姻状况			0.164	0.686
已婚	45(84.9)	352(86.9)
未婚/离异/丧偶	8(15.1)	53(13.1)
文化水平			3.535	0.316
小学及以下	17(32.1)	97(23.9)
初中	17(32.1)	143(35.3)
高中/职专	9(17.0)	106(26.2)
大专/职大及以上	10(18.8)	59(14.6)
职业			2.065	0.559
家务/待业/退休	12(22.6)	124(30.6)
农民	6(11.4)	36(8.9)
工人	15(28.3)	90(22.2)
其他^a	20(37.7)	155(38.3)
吸烟			4.422	0.035
是	31(58.5)	175(43.2)
否	22(41.5)	230(56.8)
基本特征	肝损伤组(53例)	无肝损伤组(405例)	χ²值	P值
饮酒			5.486	0.019
是	33(62.3)	183(45.2)
否	20(37.7)	222(54.8)
体力活动水平			10.832	0.004
轻度	38(71.7)	276(68.2)
中等	9(17.0)	117(28.9)
重度	6(11.3)	12(2.9)
体质量指数			12.659	0.005
<18.5	13(24.5)	35(8.6)
18.5~	25(47.2)	225(55.6)
24.0~	12(22.6)	118(29.1)
≥28.0	3(5.7)	27(6.7)
痰涂片			5.886	0.208
阴性	16(30.2)	114(28.1)
+	8(15.1)	75(18.5)
	2(3.8)	46(11.4)
+	3(5.7)	38(9.4)
	24(45.2)	132(32.6)
患者类型			1.011	0.315
复治	12(22.6)	69(17.0)
初治	41(77.4)	336(83.0)
使用保肝药			0.002	0.969
是	42(79.2)	320(79.0)
否	11(20.8)	85(21.0)
保肝药使用种类			1.701	0.427
0种	11(20.8)	85(21.0)
1~2种	28(52.8)	243(60.0)
3种及以上	14(26.4)	77(19.0)

变量	赋值	变量	赋值
血糖控制不良	否=0,是=1	体质量指数	≥18.5=0,<18.5=1
吸烟	否=0,是=1	保肝药使用情况	否=0,是=1
饮酒	否=0,是=1	贫血	否=0,是=1
体力活动水平	轻度=0,中/重度=1	膳食多样性	适中/充足=0,不足=1