早期分泌抗原靶6及免疫和炎症指标对抗结核药物性肝损伤的诊断价值

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

目的:分析相关免疫及炎症指标对抗结核药物性肝损伤的诊断价值。方法:选择2019年1月至2021年1月昆明市第三人民医院收治的符合入组标准的肺结核患者325例[包括发生抗结核药物性肝损伤的患者115例(A组)和未发生肝损伤的患者210例(B组)]和同期的门诊健康体检者98名(C组)作为研究对象。采用多因素logistic回归模型分析3组研究对象中免疫细胞、炎症指标、血清早期分泌抗原靶6(ESAT-6)及基质金属蛋白酶9(MMP-9)和MMP-14与发生抗结核药物性肝损伤的相关性。结果:A组患者年龄中位数(四分位数)[51.2(18.9,77.2)岁]高于B组[39.1(19.7,63.3)岁]和C组[36.3(20.1,61.3)岁],差异均有统计学意义(H=27.695、29.982,P值均=0.000);A组患者CD4^(+)T淋巴细胞计数[295.0(155.0,449.0)个/μl]低于B组[571.0(397.0,642.0)个/μl]和C组[775.0(710.0,993.0)个/μl],差异均有统计学意义(H=27.225、40.117,P值均=0.000);A组血浆降钙素原(PCT)[4.3(0.9,11.5)ng/ml]、D-二聚体[4.5(0.7,8.4)μg/ml]、ESAT-6[59.3(27.1,66.5)pg/ml]、MMP-9[29.1(18.6,39.6)ng/ml]表达水平均高于B组[分别为2.8(0.5,8.6)ng/ml、2.3(0.5,5.1)μg/ml、32.5(25.8,59.2)pg/ml、17.2(12.7,21.3)ng/ml],差异均有统计学意义(H=28.991、29.879、32.045、31.122,P值均=0.000);A组和B组MMP-14表达量[分别为54.7(41.4,66.7)ng/ml和60.2(45.2,65.1)ng/ml]均高于C组[5.5(2.8,6.3)ng/ml],差异均有统计学意义(H=49.209、53.436,P值均=0.000)。多因素logistic回归分析显示,高龄(>65岁)、ESAT-6升高(>30.5 pg/ml)是抗结核药物性肝损伤发生的独立危险因素[OR(95%CI)=11.289(4.355~24.361),P=0.000;OR(95%CI)=9.479(3.340~21.653),P=0.000]。结论:针对高龄和ESAT-6高表达肺结核患者及早使用保肝药物,可能会降低抗结核药物性肝损伤发生的风险。对CD4+T淋巴细胞计数较低,降钙素原、D-二聚体和MMP-9高表达的肺结核患者也应提高警惕。

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.