Analysis of serum microRNA-122 in a randomized controlled trial of N-acetylcysteine for treatment of antituberculosis drug-induced liver injury
© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society..
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 vom: 21. Juni, Seite 1844-1851 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Moosa, Muhammed Shiraz [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.05.2023 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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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): |
NLM351500847 |
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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 |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 12.05.2023 | ||
| 500 | |a Date Revised 22.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. | ||
| 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a antituberculosis drugs | |
| 650 | 4 | |a biomarkers | |
| 650 | 4 | |a liver injury | |
| 650 | 4 | |a microRNA-122 | |
| 650 | 7 | |a MIRN122 microRNA, human |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a Acetylcysteine |2 NLM | |
| 650 | 7 | |a WYQ7N0BPYC |2 NLM | |
| 650 | 7 | |a Acetaminophen |2 NLM | |
| 650 | 7 | |a 362O9ITL9D |2 NLM | |
| 650 | 7 | |a Antibiotics, Antitubercular |2 NLM | |
| 650 | 7 | |a Alanine Transaminase |2 NLM | |
| 650 | 7 | |a EC 2.6.1.2 |2 NLM | |
| 650 | 7 | |a Placebos |2 NLM | |
| 700 | 1 | |a Russomanno, Giusy |e verfasserin |4 aut | |
| 700 | 1 | |a Dorfman, Jeffrey R |e verfasserin |4 aut | |
| 700 | 1 | |a Gunter, Hannah |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Chandni |e verfasserin |4 aut | |
| 700 | 1 | |a Costello, Eithne |e verfasserin |4 aut | |
| 700 | 1 | |a Carr, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Maartens, Gary |e verfasserin |4 aut | |
| 700 | 1 | |a Pirmohamed, Munir |e verfasserin |4 aut | |
| 700 | 1 | |a Goldring, Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a Cohen, Karen |e verfasserin |4 aut | |
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