Pharmacogenetic variants and risk of remdesivir-associated liver enzyme elevations in Million Veteran Program participants hospitalized with COVID-19.

Journal Article (Journal Article)

Remdesivir is the first US Food and Drug Administration (FDA)-approved drug for the treatment of coronavirus disease 2019 (COVID-19). We conducted a retrospective pharmacogenetic study to examine remdesivir-associated liver enzyme elevation among Million Veteran Program participants hospitalized with COVID-19 between March 15, 2020, and June 30, 2021. Pharmacogene phenotypes were assigned using Stargazer. Linear regression was performed on peak log-transformed enzyme values, stratified by population, adjusted for age, sex, baseline liver enzymes, comorbidities, and 10 population-specific principal components. Patients on remdesivir had higher peak alanine aminotransferase (ALT) values following treatment initiation compared with patients not receiving remdesivir. Remdesivir administration was associated with a 33% and 24% higher peak ALT in non-Hispanic White (NHW) and non-Hispanic Black (NHB) participants (p < 0.001), respectively. In a multivariable model, NHW CYP2C19 intermediate/poor metabolizers had a 9% increased peak ALT compared with NHW normal/rapid/ultrarapid metabolizers (p = 0.015); this association was not observed in NHB participants. In summary, remdesivir-associated ALT elevations appear to be multifactorial, and further studies are needed.

Full Text

Duke Authors

Cited Authors

  • Tuteja, S; Yu, Z; Wilson, O; Chen, H-C; Wendt, F; Chung, CP; Shah, SC; Hunt, CM; Suzuki, A; Chanfreau, C; Gorman, BR; Joseph, J; Luoh, S-W; Napolioni, V; Robinson-Cohen, C; Tao, R; Zhou, J; Chang, K-M; Hung, AM; VA Million Veteran Program COVID-19 Science Initiative,

Published Date

  • August 2022

Published In

Volume / Issue

  • 15 / 8

Start / End Page

  • 1880 - 1886

PubMed ID

  • 35684976

Pubmed Central ID

  • PMC9347806

Electronic International Standard Serial Number (EISSN)

  • 1752-8062

Digital Object Identifier (DOI)

  • 10.1111/cts.13313


  • eng

Conference Location

  • United States