Development of blood biomarkers for drug-induced liver injury: an evaluation of their potential for risk assessment and diagnostics.

Abstract

Drug-induced liver injury (DILI) remains a rare but serious complication in drug therapy that is a primary cause of drug failure during clinical trials. Conventional biomarkers, particularly the serum transaminases and bilirubin, serve as useful indicators of hepatocellular or cholestatic liver injury, respectively, but only after substantial and sometimes irreversible tissue damage. Ideally, more sensitive biomarkers that respond very early before irreversible injury has occurred would offer improved outcomes. Novel biomarkers are initially being developed in animal models exposed to intrinsically hepatotoxic stimuli. However, the eventual translation to human populations, even those with known risk factors that predispose the liver to drug toxicity, would be the fundamental goal. Ultimately, some might even be applicable for the early identification of individuals predisposed to idiosyncratic hepatotoxicity potential. This article reviews recent progress in the discovery and qualification of novel biomarkers for DILI and delineates the path to eventual utilization for risk assessment. Some major categories of plasma or serum biomarkers surveyed include proteins, cytokines, circulating mRNAs, and microRNAs.

• Authors: David E Amacher, Shelli J Schomaker, Jiri Aubrecht
• Journal: Molecular diagnosis & therapy (Mol Diagn Ther) Vol. 17 Issue 6 Pg. 343-54 (Dec 2013) ISSN: 1179-2000 [Electronic] New Zealand
• PMID: 23868512 (Publication Type: Journal Article, Review)

Chemical References

• Biomarkers
• Cytokines
• MicroRNAs
• RNA, Messenger

Topics

• Animals
• Biomarkers (blood)
• Chemical and Drug Induced Liver Injury (diagnosis, genetics, metabolism)
• Cytokines (blood)
• Databases, Bibliographic
• Disease Models, Animal
• Humans
• Liver (metabolism)
• Metabolomics
• MicroRNAs (blood, metabolism)
• RNA, Messenger (blood, metabolism)
• Risk Assessment
• Risk Factors