Efficacy and Safety of Acetylcysteine for the Prevention of Liver Injury in Covid-19 Intensive Care Unit Patients Under Treatment with Remdesivir: A Double-Blind, Placebo-Controlled Randomized Clinical Trial

The objective of this double-blinded placebo-controlled randomized clinical trial was to evaluate prophylactic use of acetylcysteine for prevention of liver injury in patients with severe COVID-19 pneumonia under treatment with remdesivir.

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.

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.

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 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%) patients had serum ALT levels elevated between 1-2.5, 2.5-5 and over 5 times ULN, respectively; while in the placebo group, 24 (58.5%), 7 (17.1%) and 1 (2.4%) patients had serum ALT levels between 1-2.5, 2.5-5 and over 5 times ULN, respectively (p-value=0.073).

Intravenous administration of acetylcysteine significantly prevents liver transaminases elevation and liver injury in seriously ill COVID-19 patients treated with remdesivir. (Trial Registration: www.irct.ir identifier, IRCT20210726051995N1)