Drug-induced liver injury (DILI) is a major concern in medical practice, although infrequently it can lead to serious clinical outcomes including acute liver failure (ALF). In the US, DILI accounts for over 60% of all ALF cases and it is a major reason for high urgency liver transplantation. Importantly, over 1,000 marketed drugs, herbs, and dietary supplements have been shown to carry the potential to cause liver injury and it is a common cause for termination of drug development and drug withdrawal from the market. In the past half century, DILI has resulted in over 50 approved drugs to be either withdrawn from the market or the focus of regulatory actions including the addition of boxed warnings and other product labeling modifications.

In the upcoming special issue, we invite investigators to contribute original research articles as well as review articles that seek to address a better understanding of DILI mechanisms by considering physicochemical and toxicological properties associated with individual drugs as well as complementary alternative medicines and dietary supplements. We encourage submissions dealing with various host factors that lead to idiosyncratic toxicity and contribute to an individuals’ DILI risk. Special attention will be given to papers exploring the interactions between drug properties and host factors and their relevance to DILI outcome. We also emphatically invite submissions addressing basic and clinical research on fatty liver disease and its links to risk for DILI.

Potential topics include, but are not limited to:

• Toxicological studies
  • DILI mechanism studies for specific drugs/drug classes
  • In vitro/in vivo models such as iPSC-derived hepatocytes, 3D cell culture, humanized liver, and zebrafish
  • Toxicogenomic studies using microarray, next-generation sequencing (NGS), and microRNA expression profiles as part of Adverse Outcome Pathway (AOP) studies
  • Genetic and nongenetic biomarkers
  • Hepatotoxicity of nanomaterials
  • Bioinformatics methodologies for developing predictive models
• Regulatory science
  • DILI issues encountered in the IND, NDA, or pharmacovigilance process
• Clinical studies
  • Identifying patients at risk for DILI (AIH, viral liver disease, alcoholic liver disease, and NAFLD)
  • Host factors that contribute to assessing DILI risk
  • DILI risk in specific populations, such as diabetes mellitus, cancer, or preexisting liver diseases
  • Management of clinical DILI (e.g., how to treat DILI patients)
  • Hepatotoxicity related to herbs and dietary supplements