药物性肝损伤患者外周血清HIF1α和COX-2定量检测的临床价值

肝脏 ›› 2020, Vol. 25 ›› Issue (8): 848-852.

药物性肝损伤患者外周血清HIF1α和COX-2定量检测的临床价值

李梁, 陶应敏, 张学敏, 谢娟, 陈园

200240 上海复旦大学附属上海市第五人民医院全科医学科(李梁,陶应敏,谢娟,陈园),老年科(张学敏)

收稿日期:2020-06-20 出版日期:2020-08-31 发布日期:2020-09-04
通讯作者: 陈园,Email:ellenchenyuan@126.com
基金资助:
上海市闵行区自然科学研究基金项目(2017MHZ21)

Clinical significance of circulating hypoxia inducible factor-1α and cycloxygenase-2 in patients with drug-induced liver injury

LI Liang¹, TAO Ying-min¹, ZHANG Xue-min², XIE Juan¹, CHEN Yuan^1*

1. Department of General Practice Center, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240;
2. Department of Geriatrics, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China

Received:2020-06-20 Online:2020-08-31 Published:2020-09-04
Contact: CHEN Yuan, Email: ellenchenyuan@126.com

摘要/Abstract

摘要： 目的探讨血清中缺氧诱导因子1α(HIF1α)、环氧合酶-2(COX-2)作为药物性肝损伤(DILI)无创诊断的临床价值。方法选取2017年3月至2020年3月上海市第五人民医院收治住院的DILI患者或者在疾病治疗过程中发生的肝损伤患者60例及30名健康对照者的血清,以酶联免疫吸附法(ELISA)定量检测HIF1α和COX-2表达水平,并利用受试者工作曲线(ROC)分析其临床意义。结果 DILI患者血清中HIF1α及COX-2水平均明显高于健康对照组[(6.41±1.08)比(4.77±1.57)μg/L,(25.95±5.39)比(19.35±5.48)ng/L,均P<0.01]。但在肝细胞损伤型、胆汁淤积型、混合型3种之间,HIF1α和COX-2水平差异均无统计学意义(均P>0.05)。血清中HIF1α和COX-2水平与患者年龄分层、性别、DILI分型差异均无统计学意义。HIF1α与COX-2表达水平呈线性关系(P<0.05)。HIF1α和COX-2诊断DILI的ROC曲线下面积分别为0.894和0.820。将HIF1α临界值定为5.2 μg/L,敏感度和特异度分别为85.00%和86.67%。以19.31 ng/L作为COX-2的临界值,敏感度和特异度分别为96.67%和63.33%。合并两者ROC曲线,选取4.5 μg/L和25 ng/L分别作为HIF1α和COX-2的临界值,则敏感度为91.67％,特异度为83.33％,ROC曲线下面积为0.906。结论 HIF1α和COX-2参与DILI的发生、发展,外周血清HIF1α和COX-2水平是DILI病情评估的独立预测因子,但不能作为DILI分型的参考指标。可用于DILI无创诊断,两个指标联合诊断更具优势。

关键词: 药物性肝损伤, 缺氧诱导因子1α,环氧合酶-2, 诊断

Abstract: Objective To investigate the diagnostic values of levels of circulating hypoxia inducible factor-1α (HIF-1α) and cyclooxygenase-2 (COX-2) for drug-induced liver injury (DILI) as noninvasive methods. Methods A total of 60 DILI patients in our department from March 2017 to March 2020 were enrolled in the study. The levels of circulating HIF-1α and COX-2 were detected in these 60 DILI patients and 30 healthy controls by enzyme-linked immunosorbent assay. The diagnostic values were analyzed by receiver operator characteristic (ROC) curve. Results The serum levels of HIF-1α and COX-2 were significantly higher in DILI patients than those in healthy controls [(6.41 ± 1.08) vs (4.77 ± 1.57) μg/L, (25.95 ± 5.39) vs (19.35 ± 5.48) ng/L, both P<0.01]. In DILI patients, there was no significant difference in serum HIF-1α and COX-2 levels among hepatocellular, cholestatic and mixed types (all P > 0.05). There were no significant differences in serum HIF-1α and COX-2 levels among various age and sex, either. There was a linear relationship between HIF-1α and COX-2 expression (P<0.05). The area under the ROC curve of HIF-1α and COX-2 was 0.894 and 0.820, respectively. The cut-off value of HIF-1α for predicting DILI was 5.2 μg/L, with a sensitivity of 85.00% and a specificity of 86.67%. And the cut-off value of COX-2 was 19.31 ng/L, with a sensitivity of 96.67% and a specificity of 63.33%. After combining HIF-1α and COX-2, 4.5 μg/L and 25 ng/L were identified as the cut-off values, respectively. And the area under the ROC curve was 0.906, with a sensitivity of 91.67% and a specificity of 83.33%. Conclusion The serum levels of HIF-1α and COX-2 can serve as useful noninvasive predictive markers for the diagnosis of DILI, but not as reference for DILI classification. And the combination of the 2 has better diagnostic value.

Key words: Drug-induced liver injury, Hypoxia inducible factor-1α, Cyclooxygenase-2, Diagnosis

李梁, 陶应敏, 张学敏, 谢娟, 陈园. 药物性肝损伤患者外周血清HIF1α和COX-2定量检测的临床价值[J]. 肝脏, 2020, 25(8): 848-852.

LI Liang, TAO Ying-min, ZHANG Xue-min, XIE Juan, CHEN Yuan. Clinical significance of circulating hypoxia inducible factor-1α and cycloxygenase-2 in patients with drug-induced liver injury[J]. Chinese Hepatolgy, 2020, 25(8): 848-852.

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