Combined 5-hydroxymethylcytosine content of human leucocyte antigen-B and human leucocyte antigen-DQB1 as novel biomarker for anti-tuberculosis drug-induced liver injury.

This study investigated the diagnostic value of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) contents of human leucocyte antigen (HLA)-B and HLA-DQB1 in anti-tuberculosis drug-induced liver injury (ADLI). In total, 110 ADLI patients and 120 patients without ADLI controls were enrolled. Enzyme-linked immunosorbent assay (ELISA) was used to detect the 5-mC and 5-hmC content in DNA from peripheral blood leucocytes. The univariate analysis showed that smoking, drinking, and 5-mC and 5-hmC content of HLA-B and HLA-DQB1 were significantly associated with ADLI. After adjusting for drinking and smoking, we found that 5-mC content of HLA-B and HLA-DQB1 were associated with ADLI (odds ratio [OR] = 0.251 and 0.347, respectively) and 5-hmC contents of HLA-B and HLA-DQB1 were also associated with ADLI (OR = 1.848 and 4.705, respectively). Receiver operating characteristic (ROC) analysis indicated that the 5-hmC contents of both HLA-B and HLA-DQB1 were more clinically significant than the 5-mC contents were. The combined 5-hmC level of HLA-B and HLA-DQB1 was the best diagnostic biomarker for ADLI, with the highest areas under the curve (AUC) for 0.953, sensitivity for 0.900 and specificity for 0.875. Therefore, combined 5-hmC levels of HLA-B and HLA-DQB1 could be significant evidence for diagnosis of ADLI.