Analysis of serum microRNA‐122 in a randomized controlled trial of N‐acetylcysteine for treatment of antituberculosis drug‐induced liver injury
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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:89 |
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| Enthalten in: |
British Journal of Clinical Pharmacology - 89(2023), 6, Seite 1844-1851 |
| Beteiligte Personen: |
Moosa, Muhammed Shiraz [VerfasserIn] |
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| Anmerkungen: |
© 2023 The British Pharmacological Society |
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| Umfang: |
8 |
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| doi: |
10.1111/bcp.15661 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
WLY015147975 |
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| 100 | 1 | |a Moosa, Muhammed Shiraz |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Analysis of serum microRNA‐122 in a randomized controlled trial of N‐acetylcysteine for treatment of antituberculosis drug‐induced liver injury |
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| 520 | |a 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. | ||
| 700 | 1 | |a Russomanno, Giusy |4 aut | |
| 700 | 1 | |a Dorfman, Jeffrey R. |4 aut | |
| 700 | 1 | |a Gunter, Hannah |4 aut | |
| 700 | 1 | |a Patel, Chandni |4 aut | |
| 700 | 1 | |a Costello, Eithne |4 aut | |
| 700 | 1 | |a Carr, Dan |4 aut | |
| 700 | 1 | |a Maartens, Gary |4 aut | |
| 700 | 1 | |a Pirmohamed, Munir |4 aut | |
| 700 | 1 | |a Goldring, Christopher |4 aut | |
| 700 | 1 | |a Cohen, Karen |4 aut | |
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