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

Area of Science:

• Immunology
• Hepatology
• Vaccinology

Background:

• COVID-19 mRNA vaccines are widely used globally.
• Post-vaccination liver injury is a rare adverse event.
• Understanding the host factors influencing vaccine hepatotoxicity is crucial.

Purpose of the Study:

• To investigate the clinical characteristics, genetic predispositions, and outcomes of adults experiencing liver injury post-COVID-19 mRNA vaccination.
• To identify potential genetic associations with vaccine-induced liver injury.

Main Methods:

• Retrospective case series of 23 adults with suspected COVID-19 vaccine hepatitis.
• Causality assessment using the Drug-Induced Liver Injury Network (DILIN) expert opinion score.
• High-resolution HLA sequencing and genetic variant analysis (ERAP-2, ERAP-1).

Main Results:

• Hepatocellular injury occurred in 75% of cases, with a median onset of 16 days post-vaccination.
• Elevated liver enzymes and jaundice were observed in a significant proportion of patients.
• While autoimmune hepatitis (AIH) HLA alleles were not associated, ERAP-2 (rs1263907) and ERAP-1 Hap6 variants were significantly overrepresented in cases with high causality.

Conclusions:

• Acute liver injury following COVID-19 mRNA vaccination is uncommon and typically mild and self-limiting.
• The pathogenesis may involve a rare host immune response linked to ERAP-2 and ERAP-1 genetic variants, rather than AIH-associated HLA alleles.
• Further research into these genetic associations is warranted to understand vaccine hepatotoxicity.