Re‐evaluating variability of circulating miR‐122 in healthy volunteers: Implications for biomarker qualification in drug‐induced liver injury

Drug‐induced liver injury (DILI) remains a major challenge in clinical practice and drug development, and reliable biomarkers are still needed. MicroRNA‐122 (miR‐122) has shown promise, but reported inter‐individual variability in healthy populations has raised concerns about its clinical utility. We analysed circulating miR‐122 levels in healthy volunteers across three European sites (Antwerp, n  = 96; Brussels, n  = 124; and Leeds, n  = 60) using small RNA sequencing within the TransBioLine programme. Only modest regional differences were observed (miR‐122‐5p ICC 0.864; miR‐122‐3p ICC 0.849). Importantly, intra‐individual miR‐122 levels were stable over time (CV 10.7% and 16.5%, respectively), even under physiological perturbations such as fasting and postprandial states. Our findings suggest that previously reported miR‐122 variability may largely reflect analytical factors, including normalization strategies, rather than biological instability. miR‐122 is a robust biomarker for liver injury when appropriate analytical approaches and individual baseline levels are considered, supporting its application in clinical pharmacology and drug development.