key: cord-0909572-k2w83775
authors: Zampino, Rosa; Mele, Ferruccio; Florio, Letizia Lucia; Bertolino, Lorenzo; Andini, Roberto; Galdo, Maria; De Rosa, Rosanna; Corcione, Antonio; Durante-Mangoni, Emanuele
title: Liver injury in remdesivir-treated COVID-19 patients
date: 2020-07-28
journal: Hepatol Int
DOI: 10.1007/s12072-020-10077-3
sha: 2ca80c0de68d8e14e0cd2263dc80783707feaa42
doc_id: 909572
cord_uid: k2w83775

nan

with lopinavir/ritonavir (LPV/r, 400/100 mg twice daily po). Before and during RDV treatment, 4 of 5 patients also received hydroxychloroquine (HCQ, 200 mg twice daily po). While on RDV, no patient received acetaminophen, patient 2 and 4 received ceftazidime-avibactam plus daptomycin and patient 3 meropenem and linezolid. None of the 5 treated patients had a previous history of liver disease, visceral obesity, viral hepatitis, or prior hepatotoxic medication or alcohol intake. Liver ultrasound did not show signs of advanced liver disease. Patient 1 and 2 had a history of hypertension and asthma, respectively, but were not receiving any relevant therapy in the ICU. Figure 1 describes the dynamics of AST/ALT and bilirubin throughout the hospital stay, for each patient (Panels 1-5). In Panel 6, we report a comparison of median ALT and AST levels between RDV-treated patients and 5 COVID-19 patients who were treated in our Hospital ICU with the same schedule of LPV/r and HCQ, but without RDV. As shown in Panels 1-5, bilirubin increase occurred in 4 of 5 index patients on LPV/r. In contrast, the switch to RDV translated into a fast reduction of bilirubin and a significant increase in AST/ALT by day 3 of therapy in 4 of 5 patients. The single patient who did not receive HCQ with RDV (patient 4) did not show increase of ALT/AST levels. In no cases, RDV was discontinued because of liver injury. In patient 1, RDV was withdrawn at day 5 for a torsade de pointes requiring cardiac resuscitation, whereas patient 3 died on day 5 of RDV therapy. Final outcome was positive in 4/5 patients.

Our observation supports previous findings obtained in healthy volunteers (Gilead Sciences, data on file) and COVID-19 patients treated with RDV [4, 5] , suggesting this antiviral may cause hepatocellular injury. In our patients, this adverse effect neither progressed to severe liver damage nor induced liver failure, although none had a prior chronic liver disease. Although SARS-CoV-2 infection can cause aminotransferase elevation per se, 4 of our 5 patients had normal or slightly elevated AST/ALT levels at RDV treatment start, suggesting a direct role of RDV in hepatocellular toxicity. Despite the overall low number of patients 

A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias

Liver injury during highly pathogenic human coronavirus infections

COVID-19: an update on the epidemiological, clinical, preventive and therapeutic evidence and guidelines of integrative Chinese-western medicine for the management of 2019 novel coronavirus disease

Compassionate use of remdesivir for patients with severe covid-19

Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial