药物性肝损伤患者血清CK18-M30、HO-1、HIF-1α和Nrf2水平变化及其临床意义探讨*

doi:10.3969/j.issn.1672-5069.2025.06.017

摘要/Abstract

摘要： 目的探讨药物性肝损伤(DILI)患者血清细胞角蛋白18-M30(CK18-M30)、血红素加氧酶-1(HO-1)、缺氧诱导因子1α(HIF-1α)和核因子E2相关因子2(Nrf2)水平变化及其对诊断的临床意义。方法 2021年3月～2024年3月我院收治的83例DILI患者和同期体检的80例健康人,采用ELISA法检测血清CK18-M30、HO-1、HIF-1α和Nrf2水平,使用全自动生化分析仪检测血生化指标。构建受试者工作特征曲线(ROC)评估血清指标的诊断效能。结果本组DILI患者血清ALT、AST、ALP、GGT和TBIL水平分别为(118.5±36.1)U/L、(91.4±40.3)U/L、(193.5±46.7)U/L、(377.8±86.2)U/L和(49.8±7.3)μmol/L,均显著高于健康人(P<0.05);健康人血清CK18-M30水平为(4.9±0.2)ng/L,而DILI患者血清水平显著降低(P<0.05),血清HO-1、HIF-1α和Nrf2水平分别为(11.8±1.9)U/L、(55.4±16.3)ng/mL和(165.5±31.4)U/L,而DILI患者这些血清指标水平均显著升高(P<0.05);分别以CK18-M30、HO-1、HIF-1α和Nrf2水平为4.08 ng/L、15.40 U/L、90.53 ng/mL和501.23 U/L为截断点,以任两项达到诊断标准,结果四项血清指标联合诊断DILI的AUC为0.978(95%CI:0.952～1.000),其灵敏度为97.6%,特异度为93.2%。结论血清CK18-M30、HO-1、HIF-1α和Nrf2联合检测可以帮助诊断药物性肝损伤,对临床具有一定的应用价值。

关键词: 药物性肝损伤, 血清细胞角蛋白18-M30, 血红素加氧酶-1, 缺氧诱导因子1α, 核因子E2相关因子2, 诊断

Abstract: Objective The purpose of this study was to investigate the diagnostic efficacy of serum cytokeratin (CK)18-M30, heme oxygenase-1(HO-1), hypoxia-inducible factor 1-alpha (HIF-1α) and nuclear factor erythroid 2-related factor 2(Nrf2) levels in patients with drug-induced liver injury (DILI). Methods 83 patients with DILI and 80 healthy individuals who underwent physical examinations were enrolled in our hospital between March 2021 and March 2024, and serum CK18-M30, HO-1, HIF-1α and Nrf2 levels were detected by using ELISA. Receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic performance. Results Serum ALT, AST, ALP, GGT and bilirubin levels in patients with DILI were(118.5±36.1)U/L, (91.4±40.3)U/L, (193.5±46.7)U/L, (377.8±86.2)U/L and (49.8±7.3)μmol/L, all significantly higher than in healthy persons (P<0.05); serum CK18-M30 level in healthy control was (4.9±0.2)ng/L, much higher than in those with DILI (P<0.05), while serum HO-1, HIF-1α and Nrf2 levels were (11.8±1.9)U/L, (55.4±16.3)ng/mL and (165.5±31.4)U/L, much lower than in those with DILI(P<0.05); ROC analysis showed that the AUC was 0.978(95%CI:0.952-1.000), with sensitivity of 97.6% and specificity of 93.2%, when any two parameters of the four serum markers reached to diagnostic threshold (cut-off-value:CK18-M30=4.08 ng/L, HO-1=15.40 U/L, HIF-1α=90.53 ng/mL and Nrf2=501.23 U/L) for DILI. Conclusion The detection of serum CK18-M30, HO-1, HIF-1α and Nrf2 levels might help make diagnosis of DILI, which needs further clinical investigation.

Key words: Drug-induced liver injury, Cytokeratin 18-M30, Heme oxygenase-1, Hypoxia-inducible factor 1-alpha, Nuclear factor erythroid 2-related factor 2, Diagnosis

蒋旭燕, 吴文, 臧贝贝, 梁晓伟. 药物性肝损伤患者血清CK18-M30、HO-1、HIF-1α和Nrf2水平变化及其临床意义探讨^*[J]. 实用肝脏病杂志, 2025, 28(6): 866-869.

Jiang Xuyan, Wu Wen, Zang Beibei, et al. Implication of serum CK18-M30, HO-1, HIF-1α and Nrf2 levels in patients with drug-induced liver injury[J]. Journal of Practical Hepatology, 2025, 28(6): 866-869.

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药物性肝损伤患者血清CK18-M30、HO-1、HIF-1α和Nrf2水平变化及其临床意义探讨^*

Implication of serum CK18-M30, HO-1, HIF-1α and Nrf2 levels in patients with drug-induced liver injury

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