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Pharmacogenetic variants and risk of remdesivir-associated liver enzyme elevations in Million Veteran Program

Sony Tuteja1, Zhihong Yu2, Otis Wilson2

  • 1Corporal Michael J. Crescenz VA Medical Center and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Clinical and Translational Science
|June 10, 2022
PubMed

Insights

Remdesivir treatment for COVID-19 increased liver enzyme (ALT) levels, particularly in non-Hispanic White and Black patients. Genetic factors influenced ALT elevation in White patients, suggesting multifactorial causes.

Area of Science:

  • Pharmacogenetics
  • Hepatology
  • Infectious Diseases

Background:

  • Remdesivir is an FDA-approved antiviral for COVID-19.
  • Liver enzyme elevation is a known potential side effect.
  • Understanding genetic influences on drug response is crucial.

Purpose of the Study:

  • To investigate remdesivir-associated liver enzyme elevation in COVID-19 patients.
  • To examine pharmacogenetic factors influencing alanine aminotransferase (ALT) levels.
  • To compare ALT elevations between different racial/ethnic groups.

Main Methods:

  • Retrospective pharmacogenetic study of Million Veteran Program participants hospitalized with COVID-19.
  • Analysis of peak ALT values using linear regression, adjusted for covariates.
  • Assignment of pharmacogene phenotypes using Stargazer software.

Main Results:

  • Remdesivir use was associated with significantly higher peak ALT levels compared to non-use.
  • Non-Hispanic White and Black participants showed increased peak ALT (33% and 24%, respectively) with remdesivir.
  • Non-Hispanic White CYP2C19 intermediate/poor metabolizers had higher peak ALT (9% increase) than normal/rapid/ultrarapid metabolizers.

Conclusions:

  • Remdesivir-associated ALT elevations are multifactorial.
  • Genetic variations in CYP2C19 may influence ALT elevation in Non-Hispanic White individuals.
  • Further research is needed to fully elucidate the mechanisms behind remdesivir-induced liver enzyme changes.

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