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Researchers establish drug-induced liver injury biomarker references

Researchers established new blood-based biomarker reference intervals to assess drug-induced liver injury and recovery, according to a recently published study.

“There has been significant recent interest and investment by biomarker consortia and DILI networks to further develop and qualify novel DILI biomarker candidates that can provide added value, including mechanistic understanding, to current assessment methods,” Ben Francis, PhD, from the University of Liverpool, United Kingdom, and colleagues wrote.

To determine variation within selected biomarkers, the researchers enrolled 200 volunteers in one study on intra-variation and one study on inter-variation, and 24 volunteers in a third study on diurnal-variation.

Francis and colleagues selected the following biomarkers for the study: microRNA-122 (miR-122), Keratin-18 (K18), Glutamate Dehydrogenase (GLDH), High Mobility Group Box-1 (HMGB1), and Colony Stimulating Factor-1 (CSF-1).

The researchers observed no significant fixed effects for the selected biomarkers in intra- or inter-variation, but BMI presented a significant fixed effect in a multivariate model for miR-122 (let-7d normalized) and alanine aminotransferase.

Based on a 97.5% quantile measurement, the researchers determined the following reference intervals as significant to diurnal-variation: ALT 50 U/L (95% CI, 41-50), miR-122 3,548 copies/L (95% CI, 2,912-4,321), HMGB1 2.3 ng/mL (95% CI, 2.2-2.4), FL-K18 475 U/L (95% CI, 456-488), cc-K18 272 U/L (95% CI, 256-291), GLDH 27 U/L (95% CI, 26-30) and CSF-1 2.4 ng/mL (95% CI, 2.3-2.9).

“Correct interpretation of biomarker data is dependent on the comprehensive and accurate attainment of reference biomarker values in the healthy state and an understanding of factors that affect its variability,” the researchers wrote. “The data from the present study for the first time provide reference intervals for putative biomarkers of DILI and repair in healthy volunteers as well as robust assessments of intra-, inter- and diurnal-variability.” – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.