Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis
Program in Molecular Medicine; RNA Therapeutics Institute; Department of Medicine
Acetaminophen; Acetylcysteine; Alanine Transaminase; Hepatitis; Humans; Ischemia; MicroRNAs; Poisoning; Real-Time Polymerase Chain Reaction
Biochemistry | Digestive System Diseases | Hepatology | Molecular Biology | Molecular Genetics
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.
DOI of Published Version
Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12169-74. doi: 10.1073/pnas.1412608111. Epub 2014 Aug 4. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Ward, Jeanine; Kanchagar, Chitra; Veksler-Lublinsky, Isana; Lee, Rosalind C.; McGill, Mitchell R.; Jaeschke, Hartmut; Curry, Steven C.; and Ambros, Victor R., "Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis" (2014). Program in Molecular Medicine Publications and Presentations. 18.