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22 February 2020 : Case report  Netherlands

The MicroRNA-based Liquid Biopsy Improves Early Assessment of Lethal Acetaminophen Poisoning: A Case Report

Unusual clinical course, Challenging differential diagnosis, Diagnostic / therapeutic accidents, Adverse events of drug therapy , Clinical situation which can not be reproduced for ethical reasons

Julian Krauskopf1CDE*, Mark M. Gosink2CDE, Shelli Schomaker3BDE, Florian Caiment1C, Roscoe Warner2ADE, Kent Johnson2ABD, Jos Kleinjans1ADE, Jiri Aubrecht3ADEFG

DOI: 10.12659/AJCR.919289

Am J Case Rep 2020; 21:e919289

Abstract

BACKGROUND: Acetaminophen overdose is the most common cause of acute liver failure. Nevertheless, new biomarker approaches enabling early prediction of the outcome of the acetaminophen overdose are needed. Recently, using next-generation sequencing analysis of serum from human study participants we uncovered injury-specific signatures of circulating microRNAs (miRNAs) that represented underlying molecular mechanisms of toxicity. This case study is first to show the application of miRNA profiling to assess prognosis of acetaminophen poisoning.

CASE REPORT: The patient was admitted to the hospital following supra therapeutic acetaminophen ingestion. The patient showed elevated levels of biomarkers of hepatocellular injury alanine aminotransferase, aspartate transaminase, and glutamate dehydrogenase. Even though treatment with N-acetyl cysteine was initiated 24 hours post-ingestion, levels of alanine-aminotransferase and aspartate transaminase peaked at about 40 hours post ingestion of acetaminophen. We analyzed global circulating miRNA levels from 24 consecutive serum samples from this study participant covering the period from admission to time of death.

CONCLUSIONS: The resulting global miRNA profiles were compared with profiles from study participants with non-lethal acetaminophen poisoning and healthy controls. At the admission, the miRNA profiles of both lethal and non-lethal acetaminophen poisoning showed induction of cellular stress and oxidative damage. Later, the miRNA profiles of the lethal poisoning featured fibrosis and coagulation pathways while profiles of non-lethal cases resembled those of healthy study participants. Although additional confirmatory studies are needed, our case study is first to indicate that global miRNA profiles to be used as liquid biopsies have potential to facilitate the assessment of acetaminophen poisoning.

Keywords: Acetaminophen, Biological Markers

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American Journal of Case Reports eISSN: 1941-5923
American Journal of Case Reports eISSN: 1941-5923