P04-09 Changes in miRNA levels as biomarkers for drug-induced liver injury in human plasma

We have previously reported changes in the expression of microRNAs (miRNAs) under the administration of drugs with relatively high incidence rates of drug-induced liver injury (hTOX) and drugs with negligible risk (non-hTOX) using chimeric mice with highly humanized livers as markers for assessing the risk of DILI. In this study, we aimed to determine whether the target miRNAs showed similar changes in a clinical setting using residual blood samples obtained after therapeutic drug monitoring (TDM). This study analyzed 250 samples from 34 patients who underwent TDM for methotrexate, tacrolimus, or cyclosporine at Nagasaki University Hospital between August 3, 2021, and December 3, 2023. Quantitative real-time PCR was employed to measure the expression levels of miR-1237, miR-4306, and miR-340, with miR-320 used as an endogenous control. The expression levels of these miRNAs were compared with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels measured during TDM to analyze the behavior of each marker. Variations in the miRNA biomarkers for DILI candidates identified in chimeric mouse experiments – miR-1237, miR-4306, and miR-340 – were also observed in human plasma. In some cases, miR-1237 and miR-340 exhibited changes preceding elevations in ALT and AST levels, whereas miR-4306 tended to vary after ALT and AST increased. To validate these findings further, additional sample analysis with a larger cohort is necessary.