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血清中白细胞介素 6(IL-6)/白细胞介素 10(IL-10)/谷氨酸脱氢酶(GLDH)水平可能是抗结核药物(ATB)诱导肝损伤的早期识别标志物。

Serum levels of IL-6/IL-10/GLDH may be early recognition markers of anti-tuberculosis drugs (ATB) -induced liver injury.

机构信息

Department of Pharmacy, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.

Institute of Medical Laboratory, the First hospital of Changsha City, Changsha, Hunan 410011, China.

出版信息

Toxicol Appl Pharmacol. 2023 Sep 15;475:116635. doi: 10.1016/j.taap.2023.116635. Epub 2023 Jul 23.

Abstract

To explore the potential value of serum glutamate dehydrogenase (GLDH) combined with inflammatory cytokines as diagnostic biomarkers for anti-tuberculosis drug -induced liver injury (ATB-DILI). We collected the residual serum from the patients who met the criteria after liver function tests. We have examined these parameters including GLDH which were determined by enzyme-linked immunosorbent assay and cytokines which were determined by cytokine combination detection kit. Multivariate logistics stepwise forward regression was applied to establish regression models. A total of 138 tuberculosis patients were included in the diagnostic markers study of ATB-DILI, including normal liver function group (n = 108) and ATB-DILI group(n = 30). Serum GLDH, IL-6 and IL-10 levels were significantly increased in the ATB-DILI group. Receiver operating characteristic curve (ROC) curve showed that the area under curve (AUC) of serum GLDH, IL-6 and IL-10 for the diagnosis of ATB-DILI were 0.870, 0.714 and 0.811, respectively. In logistic regression modeling, the AUC of GLDH combined with IL-10 as an ATB-DILI marker is 0.912. Serum IL-6、IL-10 and GLDH levels began to rise preceded the increase in ALT by 7 days, with significant differences in IL-6 compared with 7 days. Serum GLDH, IL-6 and IL-10 levels were correlated with the severity of liver injury. In conclusion, we found that GLDH, IL-6 and IL-10 alone as diagnostic markers of ATB-DILI had good diagnostic efficacy. Logistic regression model established by GLDH and IL-10 had better diagnostic efficacy and IL-6 may be an early predictor of liver injury in the setting of ATB poisoning.

摘要

探讨血清谷氨酸脱氢酶(GLDH)联合炎症细胞因子作为抗结核药物性肝损伤(ATB-DILI)诊断生物标志物的潜在价值。我们收集了肝功能检查符合标准的患者的剩余血清。我们通过酶联免疫吸附试验检测了 GLDH 等参数,通过细胞因子联合检测试剂盒检测了细胞因子。采用多元逻辑逐步向前回归建立回归模型。共纳入 138 例肺结核患者,分为肝功能正常组(n=108)和 ATB-DILI 组(n=30)。ATB-DILI 组血清 GLDH、IL-6 和 IL-10 水平显著升高。受试者工作特征曲线(ROC)显示,血清 GLDH、IL-6 和 IL-10 诊断 ATB-DILI 的曲线下面积(AUC)分别为 0.870、0.714 和 0.811。在逻辑回归模型中,GLDH 联合 IL-10 作为 ATB-DILI 标志物的 AUC 为 0.912。血清 IL-6、IL-10 和 GLDH 水平在 ALT 升高前 7 天开始升高,与 7 天相比,IL-6 差异有统计学意义。血清 GLDH、IL-6 和 IL-10 水平与肝损伤严重程度相关。结论:我们发现 GLDH、IL-6 和 IL-10 单独作为 ATB-DILI 的诊断标志物具有良好的诊断效果。由 GLDH 和 IL-10 建立的逻辑回归模型具有更好的诊断效果,IL-6 可能是 ATB 中毒时肝损伤的早期预测指标。

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