Circulating microRNA Profiles in Acetaminophen Toxicity

Abstract

Introduction 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. Methods 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. Results 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. Conclusions 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.

The Role of miRNA-122 in the Early Detection of the Degree of Liver Affection in Patients with Acute Paracetamol Toxicity Admitted to The Poison Control Center Ain Shams University Hospitals

“…In the early hours post ingestion in cases of acute paracetamol toxicity, the diagnosis of acute liver injury and the initiation of antidote treatment depends mainly on paracetamol serum level plotted on Rumak Mathew nomogram as the rise in liver transaminases is not seen except several hours post ingestion (Shankar & Mehendale, 2006;Olson, 2012) The role of microRNA-122 (miRNA-122) in the early detection of liver injury in patients with acute paracetamol toxicity is an area of increasing interest, as this small non-coding RNA molecule has been found to be involved in the regulation of liver homeostasis and is highly abundant in the liver (Bandiera et al, 2015). Elevated levels of miRNA-122 in the bloodstream can be indicative of liver damage and may serve as a potential biomarker for the early detection of liver injury (Wang et al, 2009;Carreiro et al, 2020).…”

The Evolution of Circulating Biomarkers for Use in Acetaminophen/Paracetamol-Induced Liver Injury in Humans: A Scoping Review

“…Wang et al 2009 [168] first reported that serum levels of multiple miRNAs are altered in mice with APAP-induced liver injury, and these data were extended to APAP overdose patients by the research group of Kevin Park at the University of Liverpool two years later [169]. Since then, many miRNAs have been shown to increase or decrease in circulation in APAP hepatotoxicity [169][170][171][172][173][174], but miR-122 seems to display the largest and most consistent changes [175].…”