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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). 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 (SDĀ±10) years, 58 (57%) were female and 89 (87%) were HIV positive. Median time to ALT

Identiferoai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uct/oai:localhost:11427/38515
Date11 September 2023
CreatorsMoosa, Muhammed
ContributorsCohen, Karen, Maartens Gary
PublisherFaculty of Health Sciences, Department of Medicine
Source SetsSouth African National ETD Portal
LanguageEnglish
Detected LanguageEnglish
TypeDoctoral Thesis, Doctoral, PhD
Formatapplication/pdf

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