Analysis of serum microRNA-122 in a randomized controlled trial of N-acetylcysteine for treatment of antituberculosis drug-induced liver injury.

Abstract

AIM:

Serum microRNA-122 (miR-122) is a novel biomarker for drug-induced liver injury, with good sensitivity in the early diagnosis of paracetamol-induced liver injury. We describe miR-122 concentrations in participants with antituberculosis drug-induced liver injury (AT-DILI). We explored the relationship between miR-122 and alanine aminotransferase (ALT) concentrations and the effect of N-acetylcysteine (NAC) on miR-122 concentrations.

METHODS:

We included participants from a randomized placebo-controlled trial of intravenous NAC in AT-DILI. ALT and miR-122 concentrations were quantified before and after infusion of NAC/placebo. We assessed correlations between ALT and miR-122 concentrations and described changes in ALT and miR-122 concentrations between sampling occasions.

RESULTS:

We included 45 participants; mean age (± standard deviation) 38 (±10) years, 58% female and 91% HIV positive. The median (interquartile range) time between pre- and post-infusion biomarker specimens was 68 h (47-77 h). The median pre-infusion ALT and miR-122 concentrations were 420 U/L (238-580) and 0.58 pM (0.18-1.47), respectively. Pre-infusion ALT and miR-122 concentrations were correlated (Spearman's ρ = .54, P = .0001). Median fold-changes in ALT and miR-122 concentrations between sampling were 0.56 (0.43-0.69) and 0.75 (0.23-1.53), respectively, and were similar in the NAC and placebo groups (P = .40 and P = .68 respectively).

CONCLUSIONS:

miR-122 concentrations in our participants with AT-DILI were considerably higher than previously reported in healthy volunteers and in patients on antituberculosis therapy without liver injury. We did not detect an effect of NAC on miR-122 concentrations. Further research is needed to determine the utility of miR-122 in the diagnosis and management of AT-DILI.

• Authors: Muhammed Shiraz Moosa, Giusy Russomanno, Jeffrey R Dorfman, Hannah Gunter, Chandni Patel, Eithne Costello, Dan Carr, Gary Maartens, Munir Pirmohamed, Christopher Goldring, Karen Cohen
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 89 Issue 6 Pg. 1844-1851 (06 2023) ISSN: 1365-2125 [Electronic] England
• PMID: 36639145 (Publication Type: Randomized Controlled Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Chemical References

• MIRN122 microRNA, human
• MicroRNAs
• Acetylcysteine
• Acetaminophen
• Antibiotics, Antitubercular
• Alanine Transaminase
• Placebos

Topics

• MicroRNAs (blood)
• Acetylcysteine (administration & dosage)
• Chemical and Drug Induced Liver Injury (drug therapy)
• Administration, Intravenous
• Acetaminophen (adverse effects)
• Antibiotics, Antitubercular (adverse effects)
• Alanine Transaminase (blood)
• Humans
• Male
• Female
• Adult
• Placebos