ERAP-1 and ERAP-2 Variants in Liver Injury After COVID-19 mRNA Vaccination : A US Multicenter Study
Copyright © 2024 by The American College of Gastroenterology..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
The American journal of gastroenterology - (2024) vom: 25. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Fontana, Robert J [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 25.03.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.14309/ajg.0000000000002702 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368040232 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368040232 | ||
| 003 | DE-627 | ||
| 005 | 20240325234756.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240206s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.14309/ajg.0000000000002702 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1346.xml |
| 035 | |a (DE-627)NLM368040232 | ||
| 035 | |a (NLM)38314748 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Fontana, Robert J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a ERAP-1 and ERAP-2 Variants in Liver Injury After COVID-19 mRNA Vaccination |b A US Multicenter Study |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 25.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2024 by The American College of Gastroenterology. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Li, Yi Ju |e verfasserin |4 aut | |
| 700 | 1 | |a Vuppalanchi, Raj |e verfasserin |4 aut | |
| 700 | 1 | |a Kleiner, David E |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Jiezhun |e verfasserin |4 aut | |
| 700 | 1 | |a Shroff, Hersh |e verfasserin |4 aut | |
| 700 | 1 | |a Van Wagner, Lisa B |e verfasserin |4 aut | |
| 700 | 1 | |a Watkins, Paul B |e verfasserin |4 aut | |
| 700 | 0 | |a US DILIN study group |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The American journal of gastroenterology |d 1953 |g (2024) vom: 25. März |w (DE-627)NLM000025445 |x 1572-0241 |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:25 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.14309/ajg.0000000000002702 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 25 |c 03 | ||