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- Title
Analysis of serum microRNA‐122 in a randomized controlled trial of N‐acetylcysteine for treatment of antituberculosis drug‐induced liver injury.
- Authors
Moosa, Muhammed Shiraz; Russomanno, Giusy; Dorfman, Jeffrey R.; Gunter, Hannah; Patel, Chandni; Costello, Eithne; Carr, Dan; Maartens, Gary; Pirmohamed, Munir; Goldring, Christopher; Cohen, Karen
- 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.
- Subjects
ALANINE aminotransferase; RANDOMIZED controlled trials; BLOOD serum analysis; LIVER injuries; DRUG side effects; MICRORNA
- Publication
British Journal of Clinical Pharmacology, 2023, Vol 89, Issue 6, p1844
- ISSN
0306-5251
- Publication type
Article
- DOI
10.1111/bcp.15661