Biomarkers of idiosyncratic drug-induced liver injury (DILI) - a systematic review

Atallah, Edmond; Freixo, Cristiana; Alvarez-Alvarez, Ismael; Cubero, F. J.; Gerbes, Alexander L.; Kullak-Ublick, Gerd A.; Aithal, Guruprasad P.

Abstract

Introduction: Idiosyncratic drug-induced liver injury (DILI) is an unpredictable event, and there are no specific biomarkers that can distinguish DILI from alternative explanations or predict its clinical outcomes. Areas covered: This systematic review summarizes the available evidence for all biomarkers proposed to have a role in the diagnosis or prognosis of DILI. Following a comprehensive search, we included all types of studies in humans. We included DILI cases based on any threshold criteria but excluded intrinsic DILI, commonly caused by paracetamol overdose. We classified studies into diagnostic and prognostic categories and assessed their methodological quality. After reviewing the literature, 14 studies were eligible. Expert Opinion: Diagnostic studies were heterogeneous with regard to the study population and outcomes measured. Prognostic models were developed by integrating novel biomarkers, risk scores, and traditional biomarkers, which increased their prognostic ability to predict death or transplantation by 6 months. This systematic review highlights the case of need for non-genetic biomarkers that distinguish DILI from acute liver injury related to alternative etiology. Biomarkers with the potential to identify serious adverse outcomes from acute DILI should be validated in independent prospective cohorts with a substantial number of cases.

Citation

Atallah, E., Freixo, C., Alvarez-Alvarez, I., Cubero, F. J., Gerbes, A. L., Kullak-Ublick, G. A., & Aithal, G. P. (2021). Biomarkers of idiosyncratic drug-induced liver injury (DILI) - a systematic review. Expert Opinion on Drug Metabolism and Toxicology, 17(11), 1327-1343. https://doi.org/10.1080/17425255.2021.1999410

• Journal Article Type: Article
• Acceptance Date: Oct 21, 2021
• Online Publication Date: Nov 15, 2021
• Publication Date: Nov 15, 2021
• Deposit Date: Nov 25, 2021
• Publicly Available Date: Nov 26, 2021
• Journal: Expert Opinion on Drug Metabolism and Toxicology
• Print ISSN: 1742-5255
• Electronic ISSN: 1744-7607
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 17
• Issue: 11
• Pages: 1327-1343
• DOI: https://doi.org/10.1080/17425255.2021.1999410
• Keywords: Pharmacology; Toxicology; General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/6788858
• Publisher URL: https://www.tandfonline.com/doi/full/10.1080/17425255.2021.1999410