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



Moosa, Muhammed Shiraz, Russomanno, Giusy ORCID: 0000-0002-3378-5524, Dorfman, Jeffrey R, Gunter, Hannah, Patel, Chandni, Costello, Eithne, Carr, Dan, Maartens, Gary, Pirmohamed, Munir ORCID: 0000-0002-7534-7266, Goldring, Christopher
et al (show 1 more authors) (2023) Analysis of serum microRNA-122 in a randomized controlled trial of N-acetylcysteine for treatment of antituberculosis drug-induced liver injury. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 89 (6). pp. 1844-1851.

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Abstract

<h4>Aim</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.

Item Type: Article
Uncontrolled Keywords: antituberculosis drugs, biomarkers, liver injury, microRNA-122
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 13 Feb 2023 14:08
Last Modified: 12 May 2023 01:54
DOI: 10.1111/bcp.15661
Open Access URL: https://bpspubs.onlinelibrary.wiley.com/doi/10.111...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3168379