ERAP-1 and ERAP-2 Variants in Liver Injury After COVID-19 mRNA Vaccination: A US Multicenter Study
Year: 2024
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: The aim of this study is to describe the presenting features, genetic factors, and outcomes of 23 adults who developed liver injury after coronavirus disease 2019 (COVID-19) mRNA vaccination. METHODS: Patients with suspected COVID-19 vaccine hepatitis were enrolled into the Drug-Induced Liver Injury Network. Causality was assessed using the Drug-Induced Liver Injury Network expert opinion score. High-resolution HLA sequencing was undertaken using Illumina platform. RESULTS: Amongst the 16 high causality cases, median time to onset was 16 days, median age was 63 years, and 75% were female. The injury was hepatocellular in 75% with a median alanine aminotransferase of 497 U/L, and 37% had jaundice. An antinuclear antibody and smooth muscle antibody were detectable in 27% and 36%, but only 12% had an elevated immunoglobulin G level. During follow-up, 37% received a short course of corticosteroids, and 88% fully recovered by 6 months with no deaths observed. HLA alleles associated with autoimmune hepatitis were not overrepresented compared with controls, but an ERAP-2 variant (rs1263907) and the ERAP-1 Hap6 haplotype were significantly overrepresented in the high causality cases vs controls ( P = 0.026 and 5 × 10 -5 , respectively). DISCUSSION: Acute liver injury may arise within 8 weeks of COVID-19 mRNA vaccination that is generally mild and self-limited in most patients. The absence of an association with the AIH HLA alleles combined with the significant ERAP-2 and ERAP-1 Hap6 haplotype associations implicates a unique but very rare host immune response to vaccine-derived antigens in the pathogenesis of COVID-19 vaccine hepatotoxicity.
Authors: Robert J. Fontana, Yi Ju Li, Raj Vuppalanchi, David E. Kleiner, Jiezhun Gu, Hersh Shroff, Lisa B. Van Wagner, Paul B. Watkins, on behalf of the US DILIN study group
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: green
Funders: University of Southern California, Thomas Jefferson University, National Institutes of Health, National Institute on Aging, National Eye Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences, Duke Clinical Research Institute
Awards: G1436523081, IU Clinical Center: Drug Induced Liver Injury Network, G151959291, Coordinating Center for the Drug Induced Liver Injury Network (DILIN), G38283659, Mount Sinai Regional Drug Induced Liver Injury Network Site, Michigan Hepatotoxicity Clinical Research Network Renewal, General Clinical Research Center, G884701208, Herbal and Dietary Supplement Induced Liver Injury in the U.S., University of North Carolina Clinical Center for DILIN, USC-UCLA Drug-Induced Liver Injury (DILI) Clinical Center
OpenAlex ID: W4391541074