Hepatotoxicity after paracetamol overdose in a patient with cystic fibrosis despite early acetylcysteine and utility of microRNA to predict hepatotoxicity

Wong, Anselm; Cheung, Benjamin; Nejad, Charlotte; Gantier, Michael P.; Graudins, Andis

doi:10.1080/15563650.2018.1454596

Cited by 3 publications

(4 citation statements)

References 11 publications

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“…In patients developing hepatotoxicity, previous studies have shown that both miR-122 and the normalized miR-122 peak (10–20 h) earlier in comparison with ALT and could signify cessation of liver injury progression hours before a downward trend in liver aminotransferases. 13,14 This is in keeping with the few hepatotoxic patients in our study.…”

Section: Discussionsupporting

confidence: 89%

“…Serum miR-122 was normalized to miR-483 13 to account for variations of collection/purification/amplification between samples, using the following calculation (referred to as normalized miR-122 or delta miRNA 14 ): 2 −ΔCt (ΔCt = Ct miR-122 – Ct miR-483, Ct: Cycle threshold). Each RT-qPCR sample was carried out in technical duplicates.…”

Section: Methodsmentioning

confidence: 99%

“…The combination of these two miRNAs has been proposed as a better predictor of liver injury than miR-122 alone or ALT. 13,14 However, there are no studies examining the utility of miRNAs to compare acetylcysteine treatment regimens.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA from a 12-h versus 20-h acetylcysteine infusion for paracetamol overdose

et al. 2019

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Paracetamol overdose is common and microRNA (miR)-122 expression is increased with liver injury. We aimed to measure miR-122 in the setting of an abbreviated paracetamol overdose treatment regimen. We compared miRNA expression in patients treated for paracetamol poisoning with an abbreviated 12-h intravenous acetylcysteine regimen (200 mg/kg over 4 h, 50 mg/kg over 8 h) or a 20-h regimen (200 mg/kg over 4 h, 100 mg/kg over 16 h) (NACSTOP trial). miR-122 expression is increased (decreased cycle threshold (Ct) values) with paracetamol liver injury. We assessed miR-122 expression in patients receiving the two acetylcysteine regimens and in a separate group with acute liver injury (ALI). We examined 121 blood samples in 38 patients. After 20 h of acetylcysteine, median alanine transaminase (ALT) was 12 U/L (18, 14) versus 16 U/L (11, 21) ( p = 0.17) and median miR-122 Ct was 30.1 (interquartile range (IQR): 28.9, 33.3) versus 31.4 (28.9, 33.9) ( p = 0.7) in the NACSTOP abbreviated and control groups, respectively. Median normalized miR-122 Ct after 20 h of acetylcysteine was 2.2 (IQR 1.9, 6.4), 1.1 (0.7, 2.9), 63.9 (2.5, 168), 123.2 (40.9, 207.8) in the NACSTOP-abbreviated, NACSTOP-control, ALI and hepatotoxicity groups, respectively. There was no significant difference in ALT or miRNA between NACSTOP treatment groups and no signal of increased liver injury from an abbreviated 12-h acetylcysteine regimen. These findings suggest that an abbreviated acetylcysteine regimen in low-risk patients who have overdosed on paracetamol is safe. Further study is required to validate this finding utilizing miRNA as a comparative biomarker.

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Section: Discussionsupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

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MicroRNA from a 12-h versus 20-h acetylcysteine infusion for paracetamol overdose

et al. 2019

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“…Significant changes in circulating miRNA profiles of various biologic matrices (e.g., blood, urine) have been demonstrated in mouse and rat models of acetaminophen toxicity [10][11][12]. In humans, key miRNAs have been notably upregulated in urine [13], hepatocytes [14,15], and blood [15][16][17][18][19][20]. Human studies have largely focused on liver-associated miRNAs, specifically miR-122, which has repeatedly been found to be elevated in acetaminophen hepatotoxicity [21,22].…”

Section: Introductionmentioning

confidence: 99%

Circulating microRNA Profiles in Acetaminophen Toxicity

et al. 2019

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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.

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Paracetamol overdose

2018

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Hepatotoxicity after paracetamol overdose in a patient with cystic fibrosis despite early acetylcysteine and utility of microRNA to predict hepatotoxicity

Cited by 3 publications

References 11 publications

MicroRNA from a 12-h versus 20-h acetylcysteine infusion for paracetamol overdose

MicroRNA from a 12-h versus 20-h acetylcysteine infusion for paracetamol overdose

Circulating microRNA Profiles in Acetaminophen Toxicity

Paracetamol overdose

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