Liver injury in remdesivir-treated COVID-19 patients
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LETTER TO THE EDITOR
Liver injury in remdesivir‑treated COVID‑19 patients Rosa Zampino1,2 · Ferruccio Mele1 · Letizia Lucia Florio1 · Lorenzo Bertolino1 · Roberto Andini2 · Maria Galdo3 · Rosanna De Rosa4 · Antonio Corcione4 · Emanuele Durante‑Mangoni1,2 Received: 27 May 2020 / Accepted: 16 July 2020 © Asian Pacific Association for the Study of the Liver 2020
Novel Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection results predominantly in pulmonary involvement (Coronavirus disease 2019, COVID-19), but a direct, SARS-CoV-2-induced liver damage has also been described [1, 2]. Thus, it is important to monitor liver function and evaluate hepatic safety of drugs administered to COVID-19 patients. Remdesivir (RDV), a nucleotide analogue RNA polymerase inhibitor, originally developed and tested for Ebola virus disease, showed in vitro efficacy against SARS-CoV-2 [3], and experience on its efficacy and safety for COVID-19 is accumulating [4, 5]. However, hepatic safety of RDV in COVID-19 has not been the focus of detailed investigation. Here, we describe patterns of liver toxicity in 5 COVID-19 patients treated with RDV in the intensive care unit (ICU) of Monaldi Hospital, Naples, Italy, during March and April 2020. Overall, our Hospital cared for 32 critically ill COVID-19 patients. Treatment was given in a compassionate use program (CPU) approved by our Ethics Committee. CPU was limited to the first 5 patients of our center who fulfilled all eligibility criteria (invasive mechanical ventilation, no multiorgan failure, no vasopressor requirement, ALT levels 30 mL/min). RDV was administered intravenously as a 200 mg loading dose, followed by 100 mg daily over 1 h for up to 9 days. According to the early recommendations of the Italian Society for Infectious Diseases, Lombardy section, all patients had been previously treated
* Emanuele Durante‑Mangoni [email protected] 1
Internal Medicine, University of Campania ‘L. Vanvitelli’ and Units of, Napoli, Italy
2
Infectious and Transplant Medicine, AORN Ospedali dei Colli-Monaldi Hospital, Napoli, Italy
3
Pharmacy, AORN Ospedali dei Colli-Monaldi Hospital, Naples, Italy
4
Intensive Care, AORN Ospedali dei Colli-Monaldi Hospital, Naples, Italy
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 Pa
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