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Review
. 2022 May 27;23(11):6049.
doi: 10.3390/ijms23116049.

Challenges and Future of Drug-Induced Liver Injury Research-Laboratory Tests

Sabine Weber  1 , Alexander L Gerbes  1
Affiliations
Review

Challenges and Future of Drug-Induced Liver Injury Research-Laboratory Tests

Sabine Weber et al. Int J Mol Sci. .

Abstract

Drug-induced liver injury (DILI) is a rare but potentially severe adverse drug event, which is also a major cause of study cessation and market withdrawal during drug development. Since no acknowledged diagnostic tests are available, DILI diagnosis poses a major challenge both in clinical practice as well as in pharmacovigilance. Differentiation from other liver diseases and the identification of the causative agent in the case of polymedication are the main issues that clinicians and drug developers face in this regard. Thus, efforts have been made to establish diagnostic testing methods and biomarkers in order to safely diagnose DILI and ensure a distinguishment from alternative liver pathologies. This review provides an overview of the diagnostic methods used in differential diagnosis, especially with regards to autoimmune hepatitis (AIH) and drug-induced autoimmune hepatitis (DI-AIH), in vitro causality methods using individual blood samples, biomarkers for diagnosis and severity prediction, as well as experimental predictive models utilized in pre-clinical settings during drug development regimes.

Keywords: adverse drug events; biomarkers; drug development; drug-induced liver injury; hepatotoxicity.

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Conflict of interest statement

A.L.G. is co-owner of patents on an in vitro test for DILI diagnosis and causality assessment. S.W. declares no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript or in the decision to publish the results. This communication reflects the author’s view and neither IMI nor the European Union or EFPIA are responsible for any use that may be made of the information contained therein.

Figures

Figure 1
Figure 1
Example of an MH cell test result. The spiderweb graph shows the toxicity results in a patient with suspected DILI. Methylprednisolone as the likely cause of DILI in this case (causality assessment: highly likely with a positive rechallenge) induces toxicity of 60% at 2 × Cmax, of 66% at 5 × Cmax and 87% at 10 × Cmax. No toxicity of the comedication with ibuprofen, acyclovir, pantoprazole, hyperforin (a herbal remedy), ceftriaxone or prednisolone, which was used to treat the DILI episode, was observed in MH cell testing in this patient. APAP is a standard part of the test for demonstrating dose-dependent drug-induced liver injury. Lysis with 1% TWEEN®20 (polyethylene glycol sorbitan monolaurate) is used as a positive control. Abbreviations: Acic: Acyclovir; APAP: Acetaminophen; con: Negative control; CTX: Ceftriaxone; Ibu: Ibuprofen; Hyper: Hyperforin; Ibu: Ibuprofen; Methylpred: Methylprednisolone; Panto: Pantoprazole.
See this image and copyright information in PMC

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