Study participants

Participants with AT-DILI admitted to three hospitals in Cape Town, South Africa, were enrolled in a pragmatic randomised placebo-controlled trial of intravenous NAC. Anti-tuberculosis drug-induced liver injury was defined as an alanine aminotransferase (ALT) ≥ 3 times the upper limit of normal if symptoms of hepatitis were present, or an ALT ≥ 5 times the upper limit of normal without symptoms of hepatitis.⁴ Other trial inclusion criteria were age 18 years or older, taking first-line therapy for tuberculosis (TB), and liver injury attributed to ATT.

After completion of the NAC or placebo infusion, decisions regarding clinical management were made by clinicians at participating hospitals and outpatient clinics. This included decisions regarding background ATT initiation and regimen, whether to rechallenge ATT, choice of rechallenge regimen, and interrupting, rechallenging, or initiating ART. Participants were followed up until the study primary endpoint (ALT reaching < 100 U/L) was reached and ATT rechallenge was completed. We included all trial participants who were rechallenged with at least one anti-tuberculosis drug in this analysis.