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