A Randomized Controlled Trial of Intravenous N-Acetylcysteine in the Management of Anti-tuberculosis Drug-Induced Liver Injury.

ABSTRACT

BACKGROUND: Liver injury is a common complication of anti-tuberculosis therapy. N-acetylcysteine (NAC) used in patients with paracetamol toxicity with limited evidence of benefit in liver injury due to other causes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to assess the efficacy of intravenous NAC in hospitalized adult patients with anti-tuberculosis drug-induced liver injury (AT-DILI). The primary endpoint was time for serum alanine aminotransferase (ALT) to fall below 100 U/L. Secondary endpoints included length of hospital stay, in-hospital mortality, and adverse events. RESULTS: Fifty-three participants were randomized to NAC and 49 to placebo. Mean age was 38 (SD±10) years, 58 (57%) were female, 89 (87%) were HIV positive. Median (IQR) serum ALT and bilirubin at presentation were 462 (266-790) U/L and 56 (25-100) µmol/L, respectively. Median time to ALT <100 U/L was 7.5 (6-11) days in the NAC arm and 8 (5-13) days in the placebo arm. Median time to hospital discharge was shorter in the NAC arm (9 [6-15] days) than in the placebo arm (18 [10-25] days) (HR, 1.73; 95% CI, 1.13-2.65). Mortality was 14% overall and did not differ by study arm. The study infusion was stopped early due to an adverse reaction in 5 participants receiving NAC (nausea and vomiting [3], anaphylaxis [1], pain at drip site [1]). CONCLUSIONS: NAC did not shorten time to ALT <100 U/L in participants with AT-DILI, but significantly reduced length of hospital stay. NAC should be considered in management of AT-DILI. CLINICAL TRIALS REGISTRATION South African National Clinical Trials Registry (SANCTR DOH-27-0414-4719).