Differences in Glutamate Dehydrogenase (GLDH) and Other Liver Biochemistry Levels before and after Remdesivir Treatment in COVID-19

Abstract

Background: Remdesivir (RDV) is a broad-spectrum antiviral approved by the Food and Drug Administration (FDA) for the treatment of Covid-19 patients, known to have the potential to cause toxic effects on the liver. Routine monitoring of liver biochemical parameters such as AST, ALT, bilirubin, ALP and GGT, can help detect liver injury. Drug-induced liver injury, according to Hy's law, is characterized by an increase in ALT > 5x ULN, or ALP > 2x ULN, or an increase in ALT > 3x and total bilirubin > 2x ULN, simultaneously. Glutamate dehydrogenase (GLDH) is a sensitive and specific hepatic marker, which can detect liver injury and loss of mitochondrial integrity earlier than other liver biochemical parameters. This study aimed to analyze GLDH levels and liver biochemical parameters before and after RDV therapy in patients with Covid-19. We also analyze several factors that affect liver function and suggest renal function. Methods: This study used an observational analytical with a prospective cohort design, in a population of Covid-19 patients receiving RDV therapy at the infectious emergency department and isolation ward Dr. Soetomo Surabaya for September-November. Consecutive sampling was taken. The subject had drawn blood twice; once before therapy and 5 days after receiving intravenous RDV. GLDH examination is using sandwich ELISA method, while ALT, AST, ALP, GGT, direct and total bilirubin were determined spectrophotometrically. Mann-whitney, the Wilcoxon rank test and Spearman correlation test were used to analyze the data. Results: The number of samples was 34 participants with an average age of 52.47+15.21 years. Concomitant medications were dominated by n-acetylcysteine (94.1%), antioxidants (91.2%) and immunomodulators (82.4%). None of the subjects suffered liver injury induced by RDV according to Hy’s Law. Median GLDH serum levels before RDV treatment 1,14 U/L and after 5 days RDV administration 0,85 U/L (p=0,945), AST (36,4 U/L; 34, 00U/L; p=0,140), ALT (30,43 U/L; 30,20 U/L; p=0,301), DBI (0,15mg/dL; 0,24mg/dL; p=0,090), TBI (0,49mg/dL; 0,50mg/dL; p=0,567), ALP (85,0U/L; 87, 5 U/L; p=0,313) dan GGT (64,5U/L; 71,0U/L; p=0,871). The use of concomitant medication was thought to have protective properties against hepatocytes. Conclusion: After 5 days of RDV treatment, there is no evidence of liver injury. There are no significant differences in GLDH levels and other liver biomarker parameters compared to baseline. There is no difference in delta GLDH levels between groups with and without renal impairment.