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Mitochondrial-triggered immune responses mechanistically connect drug-induced steatohepatitis and cardiomyopathy associated with nonalcoholic steatohepatitis

Cellular & Molecular Immunology volume 18, pages 2078–2080 (2021)Cite this article

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In our prior publication [1], we elucidated IL-33-dependent mechanisms that regulate drug-induced liver injury. In this commentary, we mechanistically connected IL-33-dependent drug-induced steatohepatitis with nonalcoholic steatohepatitis. Drug-induced steatohepatitis (DISH) is a rare form of drug-induced liver injury caused by drugs that are capable of inducing metabolic injury, steatosis or steatohepatitis [2]. DISH is distinct from nonalcoholic steatohepatitis (NASH) because the inciting agent is known and the disease generally improves upon drug withdrawal. Although <2% of NASH cases have been attributed to DISH, evidence suggests that DISH may share pathogenic mechanisms with NASH.

NASH is an advanced form of nonalcoholic fatty liver disease (NAFLD) and is a systemic metabolic disease that is histologically characterized by male sex, steatosis, hepatitis, hepatocyte ballooning and glycogen deposition. The most common causes of death in male patients with NASH and NAFLD are cardiomyopathy, heart failure and hypertrophy [3]. However, the exact mechanisms associating NASH or NAFLD with cardiac disease have not been completely elucidated. NAFLD is the most common cause of chronic liver disease and liver transplantation worldwide [4]. Thus, successful management of NAFLD/NASH is both economically and socially significant.

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Funding

The work was supported in part by the Johns Hopkins School of Medicine Stimulating and Advancing ACCM Research (StAAR) award program.

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Authors and Affiliations

  1. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA

    Haoran Wang, Sananda Pai, Wei Dong Gao, Lakshmi Santhanam & Dolores B. Njoku

  2. Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, USA

    Shun Ishiyama, Xin Guo & Kathy Gabrielson

  3. Department of Pathology, Johns Hopkins University, Baltimore, MD, USA

    Dolores B. Njoku

  4. Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA

    Dolores B. Njoku

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  1. Haoran Wang
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  2. Sananda Pai
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  3. Shun Ishiyama
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  4. Xin Guo
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  5. Wei Dong Gao
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  6. Lakshmi Santhanam
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  7. Kathy Gabrielson
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  8. Dolores B. Njoku
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Correspondence to Dolores B. Njoku.

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Competing interests

D.B.N. is the inventor of Recognition of CYP2E1 epitopes, Patent number: 9339531, date of Patent: May 17, 2016, Assignee: The Johns Hopkins University. No funds have been received in response to this patent.

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Wang, H., Pai, S., Ishiyama, S. et al. Mitochondrial-triggered immune responses mechanistically connect drug-induced steatohepatitis and cardiomyopathy associated with nonalcoholic steatohepatitis. Cell Mol Immunol 18, 2078–2080 (2021). https://doi.org/10.1038/s41423-021-00724-6

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  • DOI: https://doi.org/10.1038/s41423-021-00724-6

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