结核菌素试验和血清载脂蛋白A1与抗结核药物性肝损伤的关系

doi:10.3969/j.issn.1004-583X.2022.01.007

摘要/Abstract

摘要：

目的探讨结核菌素(PPD)试验、血清载脂蛋白A1(apolipoprotein A-1, ApoA-1)水平与抗结核药物性肝损伤(anti-tuberculosis drug-induced liver injury, ATB-DILI)的关系。方法选取2017年1月至2021年6月于中国人民解放军联勤保障部队第九六七医院住院治疗且确诊为肺结核的患者541例,依据是否发生ATB-DILI分为病例组(56例)和对照组(485例)。记录所有患者一般临床资料。采用二元Logistic回归分析ATB-DILI发生的影响因素,采用受试者工作特征(receiver operating characteristic, ROC)曲线判断PPD试验及ApoA-1水平对ATB-DILI的预测价值。结果与对照组比较,病例组PPD试验呈强阳性的数量较多,ApoA-1水平较低,差异有统计学意义(均P<0.05)。ROC曲线显示,PPD试验强阳性、ApoA-1<1.175 g/L可以作为判断ATB-DILI的独立影响因素。结论 PPD试验反应强度和ApoA-1水平对ATB-DILI具有一定的预测价值,两者联合对ATB-DILI的预测价值更高。

关键词: 肝疾病, 结核菌素试验, 抗结核药, 载脂蛋白A-Ⅰ

Abstract:

Objective To explore the relationship between tuberculin test (PPD) with serum apolipoprotein A-1 (ApoA-1) and anti-tuberculosis drug-induced liver injury (ATB-DILI). Methods Totally 541 tuberculosis patients diagnosed at 967 Hospital of the Joint Logistics Support Force of PLA from January 2017 to June 2021 were divided into case group (56 cases) and control group (485 cases) as whether or not ATB-DILI, and the general clinical data of included subjects were recorded. Influencing factors of ATB-DILI were analyzed by binary Logistic regression, and receiver operating characteristic (ROC) curve was used to determine the predictive value of PPD test and serum ApoA-1 for ATB-DILI.Results The patients in case group were more positive PPD test, decreased ApoA-1 level as compared to the patients in control group, and with statistically significant difference between groups (all P<0.05). The ROC curve showed that strong positive PPD test and ApoA-1 level <1.175 g/L could play a part of independent factors for judging ATB-DILI. Conclusion Response intensity of PPD test and ApoA-1 level has certain predictive value for ATB-DILI, and the combination of the two displays a more higher predictive value for ATB-DILI.

Key words: liver diseases, tuberculin test, antitubercular agents, apolipoprotein A-I

中图分类号:

R575

瞿荥, 刘中洋. 结核菌素试验和血清载脂蛋白A1与抗结核药物性肝损伤的关系[J]. 临床荟萃, 2022, 37(1): 39-42.

Qu Ying, Liu Zhongyang. Relationship between tuberculin test with serum apolipoprotein A-1 and anti-tuberculosis drug-induced liver injury[J]. Clinical Focus, 2022, 37(1): 39-42.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2022.01.007

https://huicui.hebmu.edu.cn/CN/Y2022/V37/I1/39

图/表 5

参考文献 19

[1]	Song JH, Yoon SY, Park TY, et al. The clinical impact of drug-induced hepatotoxicity on anti-tuberculosis therapy: A case control study[J]. Respir Res, 2019, 20(1):283. doi: 10.1186/s12931-019-1256-y URL
[2]	沈弢, 黄昕, 王誉雅, 等. 我国药物性肝损伤流行病学研究现状[J]. 临床肝胆病杂志, 2018, 34(6):1152-1155.
[3]	Wang S, Shangguan Y, Ding C, et al. Risk factors for acute liver failure among inpatients with anti-tuberculosis drug-induced liver injury[J]. J Int Med Res, 2020, 48(1):300060518811512.
[4]	Peta V, Tse C, Perazzo H, et al. Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury DILI as biomarkers of recovery[J]. PLoS One, 2017, 12(12):e0189436.
[5]	中华人民共和国国家卫生和计划生育委员会. 肺结核诊断标准(WS 288-2017)[J]. 新发传染病电子杂志, 2018, 3(1):59-61.
[6]	中华医学会结核病学分会. 抗结核药物性肝损伤诊治指南(2019年版)[J]. 中华结核和呼吸杂志, 2019, 42(5):343-356.
[7]	Ruslami R, Gafar F, Yunivita V, et al. Pharmacokinetics and safety/tolerability of isoniazid, rifampicin and pyrazinamide in children and adolescents treated for tuberculous meningitis[J]. Arch Dis Child, 2022, 107(1):70-77.
[8]	Waddington JC, Meng X, Naisbitt DJ, et al. Immune drug-induced liver disease and drugs[J]. Current Opinion in Toxicology, 2018, 10:46-53. doi: 10.1016/j.cotox.2017.12.006 URL
[9]	Ozawa S, Miura T, Terashima J, et al. Recent progress in prediction systems for drug-induced liver injury using in vitro cell culture[J]. Drug Metab Lett, 2021, 14(1):25-40. doi: 10.2174/1872312814666201202112610 URL
[10]	Girish C, Sanjay S. Role of immune dysfunction in drug induced liver injury[J]. World J Hepatol, 2021, 13(11):1677-1687. doi: 10.4254/wjh.v13.i11.1677 URL
[11]	Liu W, Zeng X, Liu Y, et al. The immunological mechanisms and immune-based biomarkers of drug-induced liver injury[J]. Front Pharmacol, 2021, 12:723940.
[12]	朱蕾. 过敏体质与抗结核药物不良反应的相关性研究[D]. 遵义:遵义医科大学, 2019.
[13]	Burger D, Dayer JM. Cytokines, acute-phase proteins, and hormones: IL-1 and TNF-alpha production in contact-mediated activation of monocytes by T lymphocytes[J]. Ann N Y Acad Sci, 2002, 966:464-473. doi: 10.1111/nyas.2002.966.issue-1 URL
[14]	O'Connor N, Dargan PI, Jones AL. Hepatocellular damage from non-steroidal anti-inflammatory drugs[J]. QJM, 2003, 96(11):787-791. doi: 10.1093/qjmed/hcg138 URL
[15]	高磊, 权竹声, 成君, 等. 结核分枝杆菌感染检测两步法在学校结核病控制工作中的应用探讨[J]. 中华预防医学杂志, 2020, 54(4):385-391.
[16]	何翼君, 张浩然, 辛赫男, 等. 结核菌素皮肤试验的应用及其优化[J]. 中国防痨杂志, 2021, 43(3):204-210.
[17]	Chen Y, Ye P, Ren C, et al. Pharmacoeconomics of three therapeutic schemes for anti-tuberculosis therapy induced liver injury in China[J]. Open Med (Wars), 2018, 13:53-63.
[18]	阮军, 尹恒, 寇国先, 等. 异甘草酸镁治疗抗结核药物所致肝损伤疗效的Meta分析[J]. 药学实践杂志, 2019, 37(4):375-379.
[19]	张志娟, 张从玉, 姜敏, 等. 复方甘草酸苷在抗结核治疗中减少肝损伤发生率的Meta分析[J]. 药物流行病学杂志, 2018, 27(5):289-292+353.

项目	病例组 (n=56)	对照组 (n=485)	统计值	P值
年龄(岁)	33.86±15.69	34.41±10.72	t=-2.435	0.015
性别[例(%)]
男女	44(78.6) 12(21.4)	413(85.2) 72(14.8)	χ²=1.659	0.198
BMI(kg/m²)	21.72±1.25	22.08±1.86	t=-1.731	0.083
肺结核类型[例(%)]
继发性肺结核	46(82.1)	366(75.5)
结核性胸膜炎	8(3.6)	101(20.8)	χ²=1.294	0.507
血行播散性肺结核	2(14.3)	18(3.7)
PPD试验反应强度[例(%)]
阴性	1(1.8)	56(11.5)
一般阳性	3(5.4)	82(16.9)	χ²=34.569	0.000
中度阳性	7(12.5)	156(32.2)
强阳性	45(80.3)	191(39.4)
ApoA-1(g/L)	1.11±0.13	1.17±0.09	t=-5.735	0.002
ApoB(g/L)	0.83±0.14	0.86±0.13	t=-2.168	0.116
ApoB/ApoA-1	0.745±0.140	0.714±0.110	t=1.936	0.053
ALT(U/L)	22.07±8.47	20.14±9.82	t=1.671	0.085
AST(U/L)	23.04±10.53	21.31±12.17	t=1.575	0.162
GGT(U/L)	21.90±5.91	23.17±14.12	t=-1.477	0.046

项目	病例组 (n=56)	对照组 (n=485)	统计值	P值
年龄(岁)	33.86±15.69	34.41±10.72	t=-2.435	0.015
性别[例(%)]
男女	44(78.6) 12(21.4)	413(85.2) 72(14.8)	χ²=1.659	0.198
BMI(kg/m²)	21.72±1.25	22.08±1.86	t=-1.731	0.083
肺结核类型[例(%)]
继发性肺结核	46(82.1)	366(75.5)
结核性胸膜炎	8(3.6)	101(20.8)	χ²=1.294	0.507
血行播散性肺结核	2(14.3)	18(3.7)
PPD试验反应强度[例(%)]
阴性	1(1.8)	56(11.5)
一般阳性	3(5.4)	82(16.9)	χ²=34.569	0.000
中度阳性	7(12.5)	156(32.2)
强阳性	45(80.3)	191(39.4)
ApoA-1(g/L)	1.11±0.13	1.17±0.09	t=-5.735	0.002
ApoB(g/L)	0.83±0.14	0.86±0.13	t=-2.168	0.116
ApoB/ApoA-1	0.745±0.140	0.714±0.110	t=1.936	0.053
ALT(U/L)	22.07±8.47	20.14±9.82	t=1.671	0.085
AST(U/L)	23.04±10.53	21.31±12.17	t=1.575	0.162
GGT(U/L)	21.90±5.91	23.17±14.12	t=-1.477	0.046

变量	回归系数	标准误	Wald χ²值	OR值	P值	95%CI
变量	回归系数	标准误	Wald χ²值	OR值	P值	下限	上限
PPD试验反应强度^*
强阳性组^#
中度阳性组	-1.658	0.420	15.561	0.190	0.000	0.084	0.434
一般阳性组	-1.862	0.611	9.300	0.155	0.002	0.047	0.514
阴性组	-2.508	1.022	6.367	0.076	0.012	0.010	0.562
ApoA-1	-6.314	1.317	22.974	0.004	0.000	0.000	0.068
GGT	0.018	0.014	1.611	0.992	0.507	0.969	1.015
年龄	-0.005	0.013	0.122	0.995	0.727	0.970	1.021

变量	回归系数	标准误	Wald χ²值	OR值	P值	95%CI
变量	回归系数	标准误	Wald χ²值	OR值	P值	下限	上限
PPD试验反应强度^*
强阳性组^#
中度阳性组	-1.658	0.420	15.561	0.190	0.000	0.084	0.434
一般阳性组	-1.862	0.611	9.300	0.155	0.002	0.047	0.514
阴性组	-2.508	1.022	6.367	0.076	0.012	0.010	0.562
ApoA-1	-6.314	1.317	22.974	0.004	0.000	0.000	0.068
GGT	0.018	0.014	1.611	0.992	0.507	0.969	1.015
年龄	-0.005	0.013	0.122	0.995	0.727	0.970	1.021

变量	回归系数	标准误	Wald χ²值	OR值	P值	95%CI
变量	回归系数	标准误	Wald χ²值	OR值	P值	下限	上限
PPD试验反应强度^*
强阳性组^#
中度阳性组	-1.379	0.432	10.194	0.201	0.000	0.088	0.463
一般阳性组	-1.624	0.618	6.916	0.181	0.006	0.154	0.607
阴性组	-2.732	1.069	6.527	0.086	0.017	0.012	0.642
ApoA-1	-5.275	1.424	13.729	0.008	0.002	0.000	0.161