Clinical value of ESAT-6, immune and inflammatory indexes in the diagnosis of anti-tuberculosis drug-induced liver injury

doi:10.19982/j.issn.1000-6621.20220091

Abstract

Abstract: Objective: To analyze the diagnostic value of related immune and inflammatory indexes in anti-tuberculosis drug-induced liver injury.Methods: A total of 325 patients with pulmonary tuberculosis treated in the Third People’s Hospital of Kunming from January 2019 to January 2021 (including 115 patients with anti-tuberculosis drug-induced liver injury (group A) and 210 patients without liver injury (group B)) and 98 healthy outpatients in the same period (group C) were selected as subjects. Multivariate logistic regression model was used to analyze the factors related to anti-tuberculosis drug-induced liver injury in three groups: immune cells, inflammatory markers, early secretory target antigen-6 (ESAT-6), matrix metalloprotein-9 (MMP-9) and matrix metalloprotein-14 (MMP-14).Results: The age of patients in group A (51.2 (18.9, 77.2) years) was higher than that in group B (39.1 (19.7, 63.3) years) and group C (36.3 (20.1, 61.3) years), the difference was statistically significant (H=27.695,29.982; Ps=0.000). The CD4⁺ T lymphocyte count in group A patients (295.0 (155.0, 449.0) cells/μl) was lower than that in group B (571.0 (397.0, 642.0) cells/μl), and lower than that in group C (775.0 (710.0, 993.0) cells/μl), the difference were statistically significant (H=27.225, 40.117; Ps=0.000). The plasma procalcitonin (PCT)(4.3 (0.9, 11.5) ng/ml), D-dimer (4.5 (0.7, 8.4) μg/ml), ESAT-6 (59.3 (27.1, 66.5) pg/ml) and MMP-9 (29.1 (18.6, 39.6) ng/ml) in group A were higher than those of PCT (2.8 (0.5, 8.6) ng/ml), D-dimer (2.3 (0.5, 5.1) μg/ml), ESAT-6 (32.5 (25.8,59.2) pg/ml) and MMP-9 (17.2 (12.7,21.3) ng/ml) in group B, the differences were statistically significant (H=28.991, 29.879, 32.045, 31.122; Ps=0.000). The expression levels of MMP-14 in group A (54.7 (41.4, 66.7) ng/ml) and group B (60.2 (45.2, 65.1) ng/ml) were higher than those in group C (5.5 (2.8, 6.3) ng/ml). The differences were statistically significant (H=49.209,53.436; Ps=0.000). Multivariate logistic regression analysis showed that advanced age (>65 years old) and high expression of ESAT-6 (>30.5 pg/ml) were independent risk factors for the occurrence of anti-tuberculosis drug-induced liver injury (OR (95%CI)=11.289 (4.355-24.361), P=0.000; OR (95%CI)=9.479 (3.340-21.653), P=0.000).Conclusion: Early use of hepatoprotective drugs in pulmonary tuberculosis patients with advanced age and high expression of ESAT-6 may reduce the risk of anti-tuberculosis drug-induced liver injury.The vigilance should also be raised for pulmonary tuberculosis patients with low CD4⁺ T lymphocyte counts, high procalcitonin, D-dimer and MMP-9 expression.

Key words: Antitubercular agents, Drug-induced liver injury, Immunologic factors, Regression analysis

CLC Number:

LU Ni-hong, SHEN Ling-jun, LIU Hong-lu, CHEN Yang-jun, YANG Yan, DU Ying-rong. Clinical value of ESAT-6, immune and inflammatory indexes in the diagnosis of anti-tuberculosis drug-induced liver injury[J]. Chinese Journal of Antituberculosis, 2022, 44(7): 654-659. doi: 10.19982/j.issn.1000-6621.20220091

Figures/Tables 4

影响因素	β值	s $x ¯$ 值	Wald χ²值	P值	OR(95%CI)值
年龄>65岁	2.424	0.486	24.877	0.000	11.289(4.355~24.361)
CD4⁺ T淋巴细胞计数>250.0个/μl	0.093	0.112	0.689	0.406	1.098(0.881~1.367)
PCT >3.5ng/ml	0.399	0.311	1.646	0.200	1.490(0.810~2.739)
D-二聚体>4.3μg/ml	0.004	0.003	1.816	0.178	1.004(0.998~1.011)
ESAT-6 >30.5pg/ml	1.116	0.275	17.699	0.000	9.479(3.340~21.653)
MMP-9 >20.9ng/ml	-0.336	0.871	0.149	0.700	0.715(0.131~3.942)

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观察指标	A组 (115例)	B组 (210例)	C组 (98名)	H值	P值^a	H值	P值^b	H值	P值^c	H值	P值^d
CD3⁺ T淋巴细胞计数 [个/μl,M(Q₁,Q₃)]	579.0 (510.0,766.0)	647.0 (557.0,871.0)	825.0 (771.0,1125.0)	2.187	0.191	2.101	0.192	2.985	0.188	2.157	0.190
CD4⁺ T淋巴细胞计数 [个/μl,M(Q₁,Q₃)]	295.0 (155.0,449.0)	571.0 (397.0,642.0)	775.0 (710.0,993.0)	41.433	0.000	27.225	0.000	40.117	0.000	39.221	0.000
CD8⁺ T淋巴细胞计数 [个/μl,M(Q₁,Q₃)]	486.0 (412.0,565.0)	592.0 (473.0,614.0)	711.0 (536.0,801.0)	3.675	0.185	3.421	0.189	3.776	0.193	3.261	0.195
CRP [mg/L,M(Q₁,Q₃)]	15.2 (3.5,27.5)	12.8 (3.9,26.4)	8.4 (2.9,18.7)	4.832	0.126	4.552	0.131	4.773	0.122	4.235	0.133
IL-6 [pg/ml,M(Q₁,Q₃)]	24.5 (11.3,43.0)	21.2 (9.7,40.2)	15.5 (4.1,35.2)	3.211	0.179	3.785	0.165	4.232	0.159	3.114	0.171
PCT [ng/ml,M(Q₁,Q₃)]	4.3 (0.9,11.5)	2.8 (0.5,8.6)	0.02 (0.01,0.04)	36.575	0.000	28.991	0.000	34.267	0.000	32.334	0.000
D-二聚体 [μg/ml,M(Q₁,Q₃)]	4.5 (0.7,8.4)	2.3 (0.5,5.1)	0.8 (0.3,1.5)	39.641	0.000	29.879	0.000	38.213	0.000	31.285	0.000

指标	A组 (115例)	B组 (210例)	C组 (98名)	H值	H值	P值^b	H值	H值
ESAT-6 [pg/ml,M(Q₁,Q₃)]	59.3 (27.1,66.5)	32.5 (25.8,59.2)	8.3 (3.1,12.5)	41.993	32.045	0.000	42.912	38.765
MMP-9 [ng/ml,M(Q₁,Q₃)]	29.1 (18.6,39.6)	17.2 (12.7,21.3)	3.2 (1.5,3.8)	38.125	31.122	0.000	39.246	36.574
MMP-14 [ng/ml,M(Q₁,Q₃)]	54.7 (41.4,66.7)	60.2 (45.2,65.1)	5.5 (2.8,6.3)	52.631	5.628	0.257	49.209	53.436

变量	赋值	变量	赋值
CD4⁺ T淋巴细胞计数	≤250.0个/μl=0,>250.0个/μl=1	年龄	≤65岁=0,>65岁=1
PCT	≤3.5ng/ml=0,>3.5ng/ml=1	ESAT-6	≤30.5pg/ml=0,>30.5pg/ml=1
D-二聚体	≤4.3μg/ml=0,>4.3μg/ml=1	MMP-9	≤20.9ng/ml=0,>20.9ng/ml=1