254: Acetylcysteine for Treatment of Remdesivir-Induced Acute Liver Failure in COVID-19

INTRODUCTION: Remdesivir is a direct-acting nucleoside RNA polymerase inhibitor with activity against the novel SARS-CoV-2 virus used in the treatment of COVID-19 pneumonia Here we describe a case of suspected remdesivir-induced acute liver failure (ALF) successfully treated with intravenous acetylcysteine METHODS: A 68-year-old female was identified as COVID-19 positive while in the operating room undergoing multi-vessel cardiac bypass surgery While previously asymptomatic, she required intensive care unit admission for worsening oxygenation on post-operative day (POD) 2, and remdesivir was initiated On POD 3, amiodarone was initiated for new onset atrial fibrillation By POD 4 (remdesivir day 3, amiodarone day 2), the patient developed an AST/ALT of >5000 units/L each, a total bilirubin of 3 1 mg/dL, and an ammonia of 161 umol/L Remdesivir and amiodarone were discontinued and continuous infusion acetylcysteine was initiated using the 21-hour acetaminophen toxicity protocol of 150 mg/kg over 1 hour, 50 mg/kg over 4 hours, and 100 mg/kg over 16 hours By the end of the 21-hour infusion, the AST/ ALT had decreased to 1348/1861 units/L The patient's LFTs and total bilirubin returned to normal within 14 days of discontinuation of remdesivir (POD 18) The patient was discharged home with home health 4 days later (POD 22) RESULTS: Remdesivir has been reported in practice to cause transaminitis up to 5-10 times the upper limit of normal based on early clinical trials, and the Emergency Use Authorization (EUA) issued by the FDA requires ongoing monitoring of ALT throughout therapy Due to remdesivir only recently being widely used in clinical practice, the incidence of remdesivir-induced ALF is unclear Amiodarone was unlikely the cause of ALF due to very recent timing of initiation and the rapid resolution of symptoms once discontinued despite the long half-life of amiodarone While acetylcysteine is FDA approved only for acetaminophen overdose, there are small studies and case reports of its use in nonacetaminophen- induced liver failure The use of a novel, unapproved therapy through an EUA program may place patients at risk for unexpected adverse events and, in this case, the patient's acute liver failure resolved after treatment with acetylcysteine