Abstract

The hepatotoxicity of drugs is the main cause of drug withdrawal from the pharmaceutical market and interruption of the development of new molecules. Biomarkers are useful in several situations. In case of suspected drug-induced liver injury (DILI), biomarkers can be used to confirm liver damage, its severity, prognosis, confirm drug causality, or define the type of DILI. In this review, we will first present the currently used biomarkers and candidate biomarkers for the future. The current biomarkers are certainly very helpful including with the assistance of diagnostic method such the Roussel Uclaf Causality Assessment Method, but provide a limited information for the early detection of liver injury, the role of specific drug and the prediction of DILI. Some biomarkers are promising but they are not yet available for routine use. Studies are still needed to confirm their interest, particularly in comparison to Roussel Uclaf Causality Assessment Method.

Highlights

  • The hepatotoxicity of drugs is the main cause of drug withdrawal from the pharmaceutical market and interruption of the development of new molecules

  • The current biomarkers are certainly very helpful including with the assistance of diagnostic method such the Roussel Uclaf Causality Assessment Method (RUCAM), but provide a limited information for the early detection of liver injury, the role of specific drug and the prediction of drug-induced liver injury (DILI)

  • The different candidate biomarkers may be classified according to their usefulness and their comparison to RUCAM as shown in the Table 1

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Summary

Lucy Meunier and Dominique Larrey *

Liver and Transplantation Unit, Montpellier School of Medicine and IRB-INSERM-1183, Montpellier, France. Reviewed by: Jia-bo Wang, Fifth Medical Center of the PLA General Hospital, China Feng Li, Baylor College of Medicine, United States. Drug-Induced Liver Injury: Biomarkers, Requirements, Candidates, and Validation. In case of suspected drug-induced liver injury (DILI), biomarkers can be used to confirm liver damage, its severity, prognosis, confirm drug causality, or define the type of DILI. We will first present the currently used biomarkers and candidate biomarkers for the future. The current biomarkers are certainly very helpful including with the assistance of diagnostic method such the Roussel Uclaf Causality Assessment Method, but provide a limited information for the early detection of liver injury, the role of specific drug and the prediction of DILI.

INTRODUCTION
DILI Biomarkers
Diagnostic Biomarkers
Determination of the Drug or One of These Metabolites
Specific Autoantibodies
Serum Detection of Reactive Adducts
Severity Biomarkers
NOVEL CANDIDATE BIOMARKERS
No No No No No Yes
Bile Acids
Hepatobiliary Transporters
Major Histocompatibility Complex
Deregulation of Cytokines
Monocyte Derived Hepatocyte Like
In Silico Modeling of DILI
Findings
DISCUSSION
CONCLUSION
Full Text
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