Review of human risk factors for idiosyncratic drug-induced liver injury: latest advances and future goals

ABSTRACT

Introduction

Idiosyncratic drug-induced liver injury (DILI) is a common cause of acute liver injury and can lead to death from acute liver failure or require liver transplantation. Although the total burden of liver injury is high, the frequency of DILI caused by specific agents is often low. As the liver injury is by per definition idiosyncratic, the prediction of which patients will develop liver injury from specific drugs is currently a very difficult challenge.

Areas covered

The current paper highlights the most important studies on prediction of DILI published in 2019–2023, including studies on genetic, metabolomic, and demographic risk factors, concomitant medication, and the role of comorbid liver diseases. Risk stratification using demographic, metabolomic, and multigenetic risk factors is discussed.

Expert opinion

Great advances have been made in identifying genetic risk factors for DILI. Combining these risk factors with demographic information and other biomarkers into multigenetic risk models might become highly useful in risk stratifying patients exposed to DILI. However, a more detailed mapping of genetic risk factors is needed. Results of these studies need to be validated in the selected ethnic groups before applicability and cost-effectiveness can be determined.

KEYWORDS:

• DILI
• hepatotoxicity
• HLA
• liver injury
• prediction
• risk

Article highlights

• Predicting idiosyncratic drug-induced liver injury is difficult.

• Demographic information, comorbid diseases, concomitant medications, genetic risk factors, and metabolomic risk factors can in some cases be used to risk stratify patients, but the use of single risk factors yields low positive predictive values due to the rarity of this adverse event.

• Risk scores using multiple risk factors might increase the applicability and help prevent idiosyncratic DILI.

• External validation of risk factors and risk scores is important, especially when using HLA risk factors.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.