Circulating microRNA Profiles in Acetaminophen Toxicity
Acetaminophen toxicity has been associated with elevation of microRNAs. The present study was to evaluate overall microRNA profiles and previously identified microRNAs to differentiate acetaminophen (APAP) toxicity from other causes of transaminase elevation.
This was an observational study of adults with presumed acetaminophen toxicity at presentation. Serum samples were collected every 12 hours during hospitalization. Total miRNAs were extracted from plasma and levels of 327 microRNAs were quantified using real-time polymerase chain reaction. A standard measure of miRNA expression (delta-delta cycle threshold) was calculated for each microRNAs. A two-level cluster analysis was performed using a random k-means algorithm. Demographic and clinical characteristics of each cluster were compared using ANOVA, Wilcoxon rank sum, Kruskal-Wallis, and chi-square tests. Performance of specific miRNAs of interest was also evaluated.
Twenty-seven subjects were enrolled (21 with a final diagnosis of acetaminophen toxicity), and a total of 61 samples were analyzed. Five clusters were identified, two of which demonstrated clear clinical patterns and included specific elevated miRNAs previously reported to be elevated in APAP toxicity patients. Features associated with clusters 1 and 5 included confirmed acetaminophen toxicity, high peak alanine aminotransferase, and late presentation. Clusters 2–4 contained lower peak microRNAs, lower peak alanine aminotransferase, and heterogeneous clinical characteristics.
Severe cases of acetaminophen toxicity showed two distinct patterns of microRNA elevation which were similar to previous work, while less severe cases were difficult to distinguish from non-acetaminophen-associated cases. Further work is needed to incorporate microRNA profiles into the diagnostic algorithm of acetaminophen toxicity.
KeywordsAcetaminophen Drug-induced liver injury MicroRNAs Biomarkers
Sources of Funding
This work was generously sponsored by an investigator-initiated grant from McNeil Consumer Healthcare. Specimen collection, storage, and processing was provided by the University of Massachusetts Medical School/UMass Memorial Healthcare biorepository (National Center for Advancing Translational Sciences/National Institutes of Health grant number UL1TR000161).
Compliance with Ethical Standards
This protocol was reviewed and approved by the University of Massachusetts Medical School Institutional Review Board.
Conflicts of Interest
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