基于Th2型细胞因子、EOS与T淋巴细胞亚群对抗结核药致特异质性肝损伤的预测分析

摘要/Abstract

摘要： 目的探讨Th2型细胞因子、外周血嗜酸性粒细胞(EOS)及T淋巴细胞亚群在抗结核药致特异质性肝损伤患者中的表达异常情况,并评估其对不良肝损伤结局的预测价值。方法选取2021年5月至2025年5月淮安市第四人民医院接受抗结核治疗的患者93例,依据是否发生抗结核药致特异质性肝损伤分为损伤组18例和无损伤组75例。检测血清IL-4、IL-5、IL-13水平,记录EOS计数。采用流式细胞术分析CD4⁺、CD8⁺及CD4⁺/CD8⁺。比较两组一般临床资料、肝功能指标及免疫学指标。多因素logistic回归模型筛选独立危险因素。采用ROC曲线评估相关指标及其联合检测对抗结核药致特异质性肝损伤的预测效能。结果损伤组患者ALT为(156.94±54.78)U/L、AST为(121.84±36.52)U/L、TBil为(39.61±7.98)μmol/L,RUCAM评分为(9.17±3.03)分,均高于无损伤组的(49.73±8.28)U/L、(31.47±7.62)U/L、(15.84±4.26)μmol/L、(4.36±1.57)分,差异有统计学意义(均P<0.05)。损伤组 IL-4为(23.88±4.82) pg/mL、EOS为(0.74±0.24)×10⁹/L、CD4⁺/CD8⁺比值为(2.27±0.57),均高于无损伤组的(16.14±4.17) pg/mL、(0.45±0.16)×10⁹/L、(1.51±0.42),差异均有统计学意义(均 P<0.05)。多因素logistic回归分析结果显示,RUCAM评分升高(OR=2.077,95%CI:1.070~4.034,P=0.031)、IL-4水平升高(OR=1.478,95%CI:1.108~1.972,P=0.008)、EOS水平升高(OR=10.097,95%CI:2.158~47.254,P=0.003)以及CD4⁺/CD8⁺比值升高(OR=7.504,95%CI:1.809~31.132,P=0.005)均为抗结核药致特异质性肝损伤发生的独立危险因素(P<0.05)。RUCAM评分联合IL-4、EOS及CD4⁺/CD8⁺的预测效能最佳,其AUC为0.976(95%CI:0.940~1.000),灵敏度为88.9%,特异度为100.0%,约登指数为0.889,明显优于各单项指标。结论 Th2型细胞因子、EOS与T淋巴细胞亚群的免疫紊乱与抗结核药致特异质性肝损伤的发生及严重程度密切相关,其联合检测可作为评估不良肝损伤预后的重要生物学指标。

关键词: Th2型细胞因子, EOS, T淋巴细胞亚群, 抗结核药, 特异质性肝损伤

Abstract: Objective To investigate the abnormal expression of Th2 cytokines, peripheral blood eosinophils (EOS), and T-lymphocyte subsets in patients with anti-tuberculosis drug–induced idiosyncratic liver injury (ATD-ILI) and to evaluate their predictive value for adverse hepatic outcomes. Methods Ninety-three patients who received anti-tuberculosis therapy in Huai′an Fourth People′s Hospital between May 2021 and May 2025 were enrolled. According to whether ATD-ILI occurred during treatment, patients were divided into a liver injury group (n=18) and a non-injury group (n=75). Serum levels of interleukin-4 (IL-4), IL-5, and IL-13 were measured, EOS counts were recorded, and CD4⁺, CD8⁺, and CD4⁺/CD8⁺ ratios were analyzed by flow cytometry. Differences in general clinical data, liver function indices, and immunological parameters between the two groups were compared. Variables with statistical significance in univariate analysis were entered into a multivariate logistic regression model to identify independent risk factors. Receiver operating characteristic (ROC) curves were constructed to assess the predictive performance of individual indicators and their combined application for ATD-ILI. Results In the liver injury group, patients had ALT (156.94 ± 54.78 U/L), AST (121.84 ± 36.52 U/L), TBil (39.61 ± 7.98 μmol/L), and RUCAM score (9.17 ± 3.03), all of which were higher than those in the non-injury group (ALT: 49.73 ± 8.28 U/L, AST: 31.47 ± 7.62 U/L, TBil: 15.84 ± 4.26 μmol/L, RUCAM score: 4.36 ± 1.57), with statistically significant differences (all P<0.05). The liver injury group also exhibited elevated IL-4 levels (23.88 ± 4.82 pg/mL), EOS (0.74 ± 0.24 × 10⁹/L), and CD4⁺/CD8⁺ ratio (2.27 ± 0.57) compared with the non-injury group (IL-4: 16.14 ± 4.17 pg/mL, EOS: 0.45 ± 0.16 × 10⁹/L, CD4⁺/CD8⁺: 1.51 ± 0.42), all differences being statistically significant (all P<0.05). Multivariate logistic regression analysis demonstrated that increased RUCAM score (OR=2.077, 95% CI: 1.070~4.034, P=0.031), elevated IL-4 level (OR=1.478, 95% CI: 1.108~1.972, P=0.008), increased EOS (OR=10.097, 95% CI: 2.158~47.254, P=0.003), and elevated CD4⁺/CD8⁺ ratio (OR=7.504, 95% CI: 1.809~31.132, P=0.005) were independent risk factors for anti-tuberculosis drug-induced idiosyncratic liver injury (all P<0.05). The combination of RUCAM score with IL-4, EOS, and CD4⁺/CD8⁺ ratio exhibited the best predictive performance, with an AUC of 0.976 (95% CI: 0.940~1.000), sensitivity of 88.9%, specificity of 100.0%, and Youden index of 0.889, markedly outperforming individual indicators. Conclusion Immune dysregulation involving Th2 cytokines, eosinophils, and T-lymphocyte subsets is closely associated with the occurrence and severity of anti-tuberculosis drug-induced idiosyncratic liver injury. Their combined assessment provides a valuable biological tool for predicting the risk of idiosyncratic liver injury and for evaluating adverse hepatic outcomes.

Key words: Th2 cytokines, eosinophils, T-lymphocyte subsets, Anti-tuberculosis drugs, Idiosyncratic liver injury

姜红梅, 费忠亭, 杨晶月, 马雪姣. 基于Th2型细胞因子、EOS与T淋巴细胞亚群对抗结核药致特异质性肝损伤的预测分析[J]. 肝脏, 2026, 31(5): 732-736.

JIANG Hong-mei, FEI Zhong-ting, YANG Jing-yue, MA Xue-jiao. Predictive analysis of Th2 cytokines, eosinophils, and T-lymphocyte subsets for anti-tuberculosis drug-induced idiosyncratic liver injury[J]. Chinese Hepatolgy, 2026, 31(5): 732-736.

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