Translational Biomarkers of Acute Drug‐Induced Liver Injury: The Current State, Gaps, and Future Opportunities

Ozer, Josef; Reagan, William J.; Schomaker, Shelli; Palandra, Joe; Baratta, Mike; Ramaiah, Shashi K.

doi:10.1002/9780470918562.ch9

Cited by 3 publications

(1 citation statement)

References 128 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As an indicator of normal biological processes, pathogenic processes, or pharmacological responses to therapeutic intervention, biomarkers may serve as a substitute for a clinical end point and thus be a surrogate end point (Semizarov 2009b ). Biomarkers are now available for a wide range of diseases and conditions including Alzheimer's and Parkinson's disease (Maetzler and Berg 2010 ), cardiac injury (McLean and Huang 2010 ), lung injury (Kodavanti 2010 ), drug-induced liver injury (Ozer et al 2010 ), acute kidney injury (Dieterle and Sistare 2010 ), immunotoxicity (Dietert 2010 ), various cancers (Kelloff and Sigman 2012 ), pediatric care (Goldman et al 2011 ), and a host of other diseases and biological conditions.…”

Section: ■ "Omic"-enabling Technology: Microarraysmentioning

confidence: 99%

Genomics, Other “Omic” Technologies, Personalized Medicine, and Additional Biotechnology-Related Techniques

Sindelar

2013

Pharmaceutical Biotechnology

View full text Add to dashboard Cite

Section: ■ "Omic"-enabling Technology: Microarraysmentioning

confidence: 99%

Genomics, Other “Omic” Technologies, Personalized Medicine, and Additional Biotechnology-Related Techniques

Sindelar

2013

Pharmaceutical Biotechnology

View full text Add to dashboard Cite

Development of Blood Biomarkers for Drug-Induced Liver Injury: An Evaluation of Their Potential for Risk Assessment and Diagnostics

Amacher¹,

Schomaker

Aubrecht

2013

Mol Diagn Ther

View full text Add to dashboard Cite

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.

show abstract

Recommendations to Qualify Biomarker Candidates of Drug-Induced Liver Injury

et al. 2010

View full text Add to dashboard Cite

Certain compounds that induce liver injury clinically are not readily identified from earlier preclinical studies. Novel biomarkers are being sought to be applied across the pharmaceutical pipeline to fill this knowledge gap and to add increased specificity for detecting drug-induced liver injury in combination with aminotransferases (alanine and aspartate aminotransferase)--the current reference-standard biomarkers used in the clinic. The gaps in the qualification process for novel biomarkers of regulatory decision-making are assessed and compared with aminotransferase activities to guide the determination of safe compound margins for drug delivery to humans where monitoring for potential liver injury is a cause for concern. Histopathologic observations from preclinical studies are considered the principal reference standard to benchmark and assess subtle aminotransferase elevations. This approach correlates quite well for many developmental compounds, yet cases of discordance create dilemmas regarding which standard(s) indicates true injury. Concordance amongst a broader set of biomarker injury signals in a qualification paradigm will increase confidence, leading to accepted and integrated translational biomarker signals during safety assessment processes across the pharmaceutical industry, with academia, in government and in contractor laboratories.

show abstract

Translational Biomarkers of Acute Drug‐Induced Liver Injury: The Current State, Gaps, and Future Opportunities

Cited by 3 publications

References 128 publications

Genomics, Other “Omic” Technologies, Personalized Medicine, and Additional Biotechnology-Related Techniques

Genomics, Other “Omic” Technologies, Personalized Medicine, and Additional Biotechnology-Related Techniques

Development of Blood Biomarkers for Drug-Induced Liver Injury: An Evaluation of Their Potential for Risk Assessment and Diagnostics

Recommendations to Qualify Biomarker Candidates of Drug-Induced Liver Injury

Contact Info

Product

Resources

About