S5565 Rescue With Redox: An Underutilized Therapeutic Attempt in Antitubercular Therapy-Induced Liver Injury

Introduction: Antitubercular therapy-induced liver injury (AT-DILI) lacks validated treatments beyond supportive care. We present the first adult case demonstrating rapid biochemical reversal of severe AT-DILI using intravenous glutathione (GSH) after oral N-acetylcysteine (NAC) failure, averting liver transplantation. Case Description/Methods: A 35-year-old man with active pulmonary tuberculosis developed jaundice, pruritus, and coagulopathy with an international normalized ratio (INR) of 7.55 and a Model for End-Stage Liver Disease (MELD) score of 34 1-month after initiating the first-line antitubercular therapy. Transaminases peaked (aspartate aminotransferase 1597 IU/L and alanine transaminase 1368 IU/L) with a Roussel Uclaf Causality Assessment Method (RUCAM) score of 9 (highly probable). Conservative management and oral NAC (1.8 g/day) failed to improve liver parameters. We initiated intravenous GSH (1.2 g/day) for 3 days. GSH administration reduced INR to 1.31, and transaminases fell by >80% within a few days, lowering the MELD score to 13 by day 10 without any adverse events. Discussion: Unlike NAC, which may have limited efficacy in non-acetaminophen drug-induced liver injury,1 GSH replenishes hepatic redox stores, preserves Adenosine Triphosphate(ATP), and neutralizes reactive metabolites.2,3 This case highlights GSH’s potential as rescue therapy in fulminant AT-DILI, advocating for stage-stratified trials comparing GSH, NAC, and placebo. References 1. Orban C, Agapie M, Bratu A, et al. No significant beneficial effects of intravenous n-acetylcysteine on patient outcome in non-paracetamol acute liver failure: A meta-analysis of randomized controlled trials. Biomedicines. 2024;12(7):1462. 2. Saito C, Zwingmann C, Jaeschke H. Novel mechanisms of protection against acetaminophen hepatotoxicity in mice by glutathione and N-acetylcysteine. Hepatology. 2010;51(1):246-54. 3. Aldini G, Altomare A, Baron G, Vistoli G, Carini M, Borsani L, Sergio F. N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why. Free Radic Res. 2018 Jul;52(7):751-762.