Abstract: Gastroenterology and Hepatology From Bed to Bench. ©2022 RIGLD, Research Institute for Gastroenterology and Liver Diseases ORIGINAL ARTICLE Efficacy and safety of acetylcysteine for the prevention of liver injury in COVID-19 intensive care unit patients under treatment with remdesivir Pouria Mousapour1, Ramin Hamidi Farahani2, Reza Mosaed3, Ali Asgari2, Ebrahim Hazrati1 1 Department of Anesthesiology and Intensive Care, AJA University of Medical Sciences, Tehran, Iran 2 Department of Infectious Diseases, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran 3 Department of Clinical Pharmacy, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran ABSTRACT Aim: The present double-blinded placebo-controlled randomized clinical trial evaluated prophylactic use of acetylcysteine for the prevention of liver injury in patients with severe COVID-19 pneumonia under treatment with remdesivir. Background: Liver injury is reportedly common in patients with severe COVID-19 pneumonia and can occur not only as a result of disease progression, but as an iatrogenic reaction to remdesivir. Methods: A total of 83 adult patients with severe COVID-19 pneumonia were randomly assigned in parallel groups to receive either acetylcysteine or placebo. All the patients received standard care according to institutional protocols, including remdesivir for a total of five days. One gram acetylcysteine was administered intravenously every 12 hours for 42 patients, and 41 patients received the same volume of 0.9% sodium chloride as placebo (Trial Registration: www.irct.ir identifier, IRCT20210726051995N1). Results: After 5 days, median aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly lower in the acetylcysteine than in the placebo group. Of those who received the placebo, 30 (73.2%), 4 (9.7%), and 3 (7.3%) patients had serum AST levels elevated between 1-2.5, 2.5-5, and over 5 times the upper limit of normal (ULN), respectively; while in the acetylcysteine group, 33 (78.6%) and 0 patients had AST levels between 1-2.5 and over 2.5 times ULN, respectively (p-value=0.037). In the acetylcysteine group, 23 (54.8%), 1 (2.4%), and 1 (2.4%) patient had serum ALT levels elevated between 1-2.5, 2.5-5, and over 5 times ULN, respectively; in the placebo group, however, 24 (58.5%), 7 (17.1%), and 1 (2.4%) patient had serum ALT levels between 1-2.5, 2.5-5, and over 5 times ULN, respectively (p-value=0.073). Conclusion: Intravenous administration of acetylcysteine significantly prevents liver transaminases elevation and liver injury in seriously ill COVID-19 patients treated with remdesivir. Keywords: COVID-19, Coronavirus, Liver injury, Acetylcysteine, Remdesivir, Clinical trial. (Please cite as: Mousapour P, Hamidi Farahani R, Mosaed R, Asgari A, Hazrati E. Efficacy and safety of acetylcysteine for the prevention of liver injury in COVID-19 intensive care unit patients under treatment with remdesivir. Gastroenterol Hepatol Bed Bench 2022;15(3):241-248).