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Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis.

Authors
  • Ward, Jeanine
  • Kanchagar, Chitra
  • Veksler-Lublinsky, Isana
  • Lee, Rosalind C
  • McGill, Mitchell R
  • Jaeschke, Hartmut
  • Curry, Steven C
  • Ambros, Victor R
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
Aug 19, 2014
Volume
111
Issue
33
Pages
12169–12174
Identifiers
DOI: 10.1073/pnas.1412608111
PMID: 25092309
Source
Medline
Keywords
License
Unknown

Abstract

We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRNAs decrease toward normal levels during treatment with N-acetyl cysteine (NAC). We identified a set of 11 miRNAs whose profiles and dynamics in the circulation during NAC treatment can discriminate APAP hepatotoxicity from ischemic hepatitis. The elevation of certain miRNAs can precede the dramatic rise in the standard biomarker, alanine aminotransferase (ALT), and these miRNAs also respond more rapidly than ALT to successful treatment. Our results suggest that miRNAs can serve as sensitive diagnostic and prognostic clinical tools for severe liver injury and could be useful for monitoring drug-induced liver injury during drug discovery.

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