S2597 A Case of Acute Liver Failure Secondary to Remdesivir in the Treatment of SARS-CoV-2

Abstract

Introduction: To date, there have been over 32 million cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United States alone. Remdesivir is the only drug approved by the US Food and Drug Administration for the treatment of SARS-CoV-2. Although safety data is limited, hepatotoxicity has been reported in 5-37% with most cases being mild. We present a case of acute liver failure (ALF) from remdesivir, successfully treated with N-acetylcysteine (NAC) infusion. Case Description/Methods: An 83-year-old obese male with chronic kidney and cardiac disease presented with cough and diarrhea for one week and was diagnosed with SARS-CoV-2. Due to hypoxemia, he was started on remdesivir and dexamethasone on hospital day 1. Compared to normal transaminases on admission, on hospital day 6, the patient had an acute elevation of his aspartate aminotransferase (AST) to 3539, alanine aminotransferase (ALT) to 2246, international normalized ratio (INR) to 4.77 and mild elevations in alkaline phosphatase (ALP) to 207 and total bilirubin to 2.9. This was consistent with a hepatocellular pattern of injury. He concurrently developed altered mental status with no asterixis. Acute viral hepatitis serologies and autoimmune markers were negative and liver ultrasound demonstrated a patent portal vein and normal biliary ducts. Remdesivir and dexamethasone were discontinued. Intravenous vitamin K was administered to reverse his coagulopathy and a 5-day course of NAC was completed. The patient had significant improvement in his mental status, AST, ALT, and INR within 24 hours of NAC initiation, with continued improvement over the next two weeks of hospitalization (Figure 1a,b). Discussion: Transaminase elevation is a known side effect of remdesivir, and close monitoring of liver tests is recommended. However, ALF is a rare complication with only two other published cases and with no approved therapy. In our case of an elderly gentleman with SARS-CoV-2 who developed ALF with grade 1 encephalopathy 6 days after initiation of remdesivir, the discontinuation of the drug along with NAC treatment was successful in reversing the ALF. Furthermore, this patient's obesity may have increased his risk of Remdesivir hepatotoxicity through impaired cytochrome P450 metabolism. While seemingly rare, more research on the mechanism and risk profile of remdesivir hepatotoxicity is needed as this drug becomes more commonly used in the treatment of SARS-CoV-2. (Figure Presented).