Usefulness of plasma bile acid profile as a prognostic biomarker for drug-induced liver injury

BACKGROUND: The liver maintains bile acid (BA) homoeostasis; circulating BA levels are used as a biomarker in certain cholestatic conditions. BAs can initiate processes in the pathogenesis of drug-induced liver injury (DILI), an unpredictable occurrence which can lead to liver failure. As such, this study aimed to explore whether changes in plasma BA profiles can serve as useful biomarkers for diagnostic and prognostic purposes in patients presenting with suspected DILI. METHODS: In a prospective, nested case-control observational study, patients presenting with acute liver injury potentially due to DILI were sampled and followed through standard clinical care with severity and outcomes monitored. After review, cases were adjudicated as DILI or nonDILI (alternate causes). Plasma BA levels and profile were quantified and compared to those in healthy volunteers (n = 25). FINDINGS: Total plasma BA levels in patients with DILI (n = 120) were significantly elevated compared to healthy volunteers; the nonDILI group (n = 49) also displayed marked hypercholanemia. Higher values of total, primary, and conjugated BAs at presentation, were associated with liver injury that was likely to progress in severity. The ratios of primary-to-secondary BAs and (cholic acid + deoxycholic acid) to (chenodeoxycholic acid + lithocholic acid) improved the prognostic value of the model for end-stage liver disease (MELD) score. INTERPRETATION: BA profiling could be useful for the early detection of patients where DILI is likely to become more severe and those with outcomes of death or liver transplantation. Further investigation in another independent longitudinal study is needed to validate this biomarker. FUNDING: IMI2 821283; IS-BRC-1215-20003.