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Drug-Induced Steatosis and Steatohepatitis: The Search for Novel Serum Biomarkers Among Potential Biomarkers for Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis

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Abstract

Drug-induced steatosis (DIS) and drug-induced steatohepatitis (DISH) are two of several types of drug-induced liver injury (DILI). They can be caused by various drugs and may present as acute, potentially lethal disorders or as chronic slowly progressive liver injury. Despite the fact that they are distinct disorders, the slow progressive forms of DIS and DISH are often confused with or misdiagnosed as non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), which are much more common and, by definition, not caused by drugs. Currently the only way to identify DIS is via imaging studies or a liver biopsy, while DISH can be identified only through liver biopsy. In addition, diagnosis of either DIS or DISH requires an exhaustive clinical evaluation and comprehensive causality assessment to rule out other possible causes and determine the association with the suspected drug. Furthermore, it is difficult, using existing methods, to monitor the progression of DIS and DISH and to determine the underlying mechanism. Therefore, there is a great unmet need for non-invasive biomarkers that will be able to identify the development of DIS or DISH during drug development and to monitor for progression or regression of the disorder during treatment or following drug discontinuation. Recent developments in the fields of NAFLD and NASH have introduced several novel biomarkers that show promise for the diagnosis, monitoring, and severity assessment of these common diseases. Given the significant overlap in possible underlying mechanisms and histological pattern between NAFLD/NASH and DIS/DISH, these postulated NAFLD and NASH biomarkers may have a potential application to DIS and DISH. This article reviews the existing medical literature and other publically available information pertaining to novel serum biomarkers for NAFLD and NASH, and explores the concurrent identification of these biomarkers for DIS and DISH.

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Acknowledgements

The authors thank Natasha Cole for her help in the preparation of this review paper.

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Authors and Affiliations

  1. Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA

    Lauren Pavlik

  2. Eli Lilly and Company, Indianapolis, IN, USA

    Arie Regev & Paul A. Ardayfio

  3. Indiana University School of Medicine, Indianapolis, IN, USA

    Naga P. Chalasani

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  1. Lauren Pavlik
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  2. Arie Regev
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  3. Paul A. Ardayfio
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  4. Naga P. Chalasani
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Correspondence to Arie Regev.

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Conflict of interest

Dr. Lauren Pavlik has no conflicts of interest related to this paper. Dr. Naga Chalasani serves as a consultant to several pharmaceutical companies for activities related to NAFLD and DILI, but has no conflicts of interest that are directly relevant to the content of this paper. Dr. Arie Regev and Dr. Paul Ardayfio are full-time employees of Eli Lilly, but have no conflicts of interest that are directly relevant to the content of this paper.

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Pavlik, L., Regev, A., Ardayfio, P.A. et al. Drug-Induced Steatosis and Steatohepatitis: The Search for Novel Serum Biomarkers Among Potential Biomarkers for Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis. Drug Saf 42, 701–711 (2019). https://doi.org/10.1007/s40264-018-00790-2

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