Immune-mediated hepatitis with the Moderna vaccine, no longer a coincidence but confirmed

This case illustrates immune-mediated hepatitis secondary to the Moderna vaccine, which on inadvertent re-exposure led to worsening liver injury with deranged synthetic function. This occurred in a well man with no other medical problems. The onset of jaundice associated with the mRNA vaccine was unusually rapid. This was also illustrated in the other cases where symptoms developed over a median of 7 days (range 4-35). Latency is usually longer in other causes of DILI, but can vary depending on mode of injury.
The mRNA vaccine pathway triggers pro-inflammatory cytokines including interferon and cross-reactivity has been illustrated between the antibodies against the spike protein and self-antigens

Seven cases of suspected immune-mediated hepatitis have been reported with SARS-2-COV mRNA vaccines (3 with Pfizer and 4 with Moderna).1, 2, 3, 4, 5, 6, 7 Liver histology was assessed in every case and findings were similar to ours, indicating acute hepatitis with interface hepatitis, lymphoplasmacytic infiltrate and absence of fibrosis. Eosinophils as part of the infiltrate, which can be noted in DILI were present in 3 cases. All 7 patients responded well to steroids (n = 5 prednisolone, n = 1 budesonide and n = 1 methylprednisolone). In 3 cases there were features suggesting coincidental autoimmune hepatitis: a 35-year-old lady in her third trimester of pregnancy with positive double-stranded DNA, an 80-year-old lady with a history of autoimmune conditions and a 41-year-old lady with strongly positive auto-antibody panel after both doses of vaccination. In the other 4 cases, a raised IgG, with at least 1 positive antibody was noted in 3 cases.4, 5, 6, 7
This case has confirmed immune-mediated hepatitis secondary to the Moderna vaccine, which on inadvertent re-exposure led to acute severe hepatitis. Treatment with corticosteroid therapy appears to be favourable. We wish to highlight that immune-mediated reactions from the SARS-CoV-2 mRNA vaccines are very rare and during the COVID pandemic, the vaccination programme continues to be crucial. We report this case to encourage vigilance for drug-induced reactions and to raise awareness to vaccination centres to incorporate it into their routine checks before administering second doses. Long-term follow up of identified individuals will be essential in determining the prognosis of this immune-mediated liver injury.