Novel circulating- and imaging-based biomarkers to enhance the mechanistic understanding of human drug-induced liver injury

Liver safety biomarkers in current clinical practice are recognized to have certain shortcomings including their representation of general cell death and thus lacking in indicating the specific underlying mechanisms of injury. An informative panel of circulating- and imaging-based biomarkers, will allow a more complete understanding of the processes involved in the complex and multi-cellular disease of drug-induced liver injury; potentially preceding and therefore enabling prediction of disease progression as well as directing appropriate, existing or novel, therapeutic strategies. Several putative liver safety biomarkers are under investigation as discussed throughout this review, informing on a multitude of hepatocellular mechanisms including: early cell death (miR-122), necrosis (HMGB1, K18), apoptosis, (K18), inflammation (HMGB1), mitochondrial damage (GLDH, mtDNA), liver dysfunction (MRI, MSOT) and regeneration (CSF1). These biomarkers also hold translational value to provide important read across between in vitro-in vivo and clinical test systems. However, gaps in our knowledge remain requiring further focussed research and the ultimate qualification of key exploratory biomarkers. Relevance for patients: this novel multi-modal approach of assessing drug-induced liver injury could potentially enable better patient stratification and enhance treatment strategies. Ultimately, this could reduce unnecessary treatment, also decreasing hospital bed occupancy, whilst ensuring early and accurate identification of patients needing intervention.