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A randomised controlled trial of N-acetylcysteine in the management of anti-tuberculosis drug-induced liver injury
Background: Liver injury is the most common severe adverse effect of first-line anti-tuberculosis therapy (ATT). Nacetylcysteine (NAC) has efficacy in patients with paracetamol toxicity, and may be of benefit in liver injury due to other causes, such as ATT-induced liver injury (AT-DILI). Rechalleng...
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| Format: | Thesis |
| Language: | English |
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Department of Medicine
2023
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| _version_ | 1867611268279435264 |
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| access_status_str | Open Access |
| author | Moosa, Muhammed |
| author2 | Cohen, Karen |
| author_browse | Cohen, Karen Moosa, Muhammed |
| author_facet | Cohen, Karen Moosa, Muhammed |
| author_sort | Moosa, Muhammed |
| collection | Thesis |
| description | Background: Liver injury is the most common severe adverse effect of first-line anti-tuberculosis therapy (ATT). Nacetylcysteine (NAC) has efficacy in patients with paracetamol toxicity, and may be of benefit in liver injury due to other causes, such as ATT-induced liver injury (AT-DILI). Rechallenge of first line ATT after liver injury is usually attempted and may result in recurrence of liver injury. Alanine transaminase (ALT) is the biomarker currently used in AT-DILI diagnosis. MicroRNA-122 (miR-122) is a sensitive biomarker for liver injury due to paracetamol, but data on utility as a biomarker for ATDILI are limited. Methods: We conducted a randomized double-blind placebo-controlled trial of intravenous NAC in adult hospitalized participants with AT-DILI. Primary endpoint was time to ALT < 100 U/L; secondary endpoints included length of hospital stay and 8-week mortality. We described outcomes of ATT rechallenge following AT-DILI. We quantified miR-122 and ALT concentrations before and after infusion of NAC/placebo, and explored the effect of NAC on miR-122. Results We enrolled 102 participants with AT-DILI, 53 randomized to NAC and 49 to placebo. Mean age was 38 (SD±10) years, 58 (57%) were female and 89 (87%) were HIV positive. Median time to ALT |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/38515 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| publisher | Department of Medicine |
| publisherStr | Department of Medicine |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/38515 A randomised controlled trial of N-acetylcysteine in the management of anti-tuberculosis drug-induced liver injury Moosa, Muhammed Cohen, Karen Maartens Gary Liver injury Nacetylcysteine (NAC) Background: Liver injury is the most common severe adverse effect of first-line anti-tuberculosis therapy (ATT). Nacetylcysteine (NAC) has efficacy in patients with paracetamol toxicity, and may be of benefit in liver injury due to other causes, such as ATT-induced liver injury (AT-DILI). Rechallenge of first line ATT after liver injury is usually attempted and may result in recurrence of liver injury. Alanine transaminase (ALT) is the biomarker currently used in AT-DILI diagnosis. MicroRNA-122 (miR-122) is a sensitive biomarker for liver injury due to paracetamol, but data on utility as a biomarker for ATDILI are limited. Methods: We conducted a randomized double-blind placebo-controlled trial of intravenous NAC in adult hospitalized participants with AT-DILI. Primary endpoint was time to ALT < 100 U/L; secondary endpoints included length of hospital stay and 8-week mortality. We described outcomes of ATT rechallenge following AT-DILI. We quantified miR-122 and ALT concentrations before and after infusion of NAC/placebo, and explored the effect of NAC on miR-122. Results We enrolled 102 participants with AT-DILI, 53 randomized to NAC and 49 to placebo. Mean age was 38 (SD±10) years, 58 (57%) were female and 89 (87%) were HIV positive. Median time to ALT 2023-09-11T13:17:11Z 2023-09-11T13:17:11Z 2023 2023-09-11T13:07:43Z Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/38515 eng application/pdf Department of Medicine Faculty of Health Sciences |
| spellingShingle | Liver injury Nacetylcysteine (NAC) Moosa, Muhammed A randomised controlled trial of N-acetylcysteine in the management of anti-tuberculosis drug-induced liver injury |
| thesis_degree_str | Doctoral |
| title | A randomised controlled trial of N-acetylcysteine in the management of anti-tuberculosis drug-induced liver injury |
| title_full | A randomised controlled trial of N-acetylcysteine in the management of anti-tuberculosis drug-induced liver injury |
| title_fullStr | A randomised controlled trial of N-acetylcysteine in the management of anti-tuberculosis drug-induced liver injury |
| title_full_unstemmed | A randomised controlled trial of N-acetylcysteine in the management of anti-tuberculosis drug-induced liver injury |
| title_short | A randomised controlled trial of N-acetylcysteine in the management of anti-tuberculosis drug-induced liver injury |
| title_sort | randomised controlled trial of n acetylcysteine in the management of anti tuberculosis drug induced liver injury |
| topic | Liver injury Nacetylcysteine (NAC) |
| url | http://hdl.handle.net/11427/38515 |
| work_keys_str_mv | AT moosamuhammed arandomisedcontrolledtrialofnacetylcysteineinthemanagementofantituberculosisdruginducedliverinjury AT moosamuhammed randomisedcontrolledtrialofnacetylcysteineinthemanagementofantituberculosisdruginducedliverinjury |