ERAP-1 and ERAP-2 Variants in Liver Injury After COVID-19 mRNA Vaccination: A US Multicenter Study.

Autor:	Fontana RJ; Division of Gastroenterology and Hepatology, University of Michigan Medical School, Ann Arbor, Michigan, USA., Li YJ; Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, USA., Vuppalanchi R; Department of Medicine, Indiana University, Indianapolis, Indiana, USA., Kleiner DE; Laboratory of Pathology, National Cancer Institute (NCI), Bethesda, Maryland, USA., Gu J; Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA., Shroff H; Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA., Van Wagner LB; Division of Digestive Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA ., Watkins PB; Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Jazyk:	angličtina
Zdroj:	The American journal of gastroenterology [Am J Gastroenterol] 2024 Aug 01; Vol. 119 (8), pp. 1496-1505. Date of Electronic Publication: 2024 Feb 05.
DOI:	10.14309/ajg.0000000000002702
Abstrakt:	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. (Copyright © 2024 by The American College of Gastroenterology.)
Databáze:	MEDLINE
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