Comment on "Autoimmune hepatitis developing after coronavirus disease 2019 (COVID-19) vaccine: Causality or casualty?"

To the Editor:

We read with great interest the article by Bril F. et al. recently published in the Journal of Hepatology. In our opinion, several considerations increase the possibility that the described association is indeed coincidental, as also acknowledged by the authors.

The patient was a 35-year-old Caucasian female on her 3rd month postpartum under treatment with labetalol for gestational hypertension. Symptoms developed 6 days after vaccination. The presence of eosinophils at liver histology seems to preferentially support the possibility of a drug- or toxin-induced liver injury, even if the marked lymphoplasmacytic infiltrate is more common in immune-mediated liver diseases.

While immune reactions to vaccines are rather common, the association with the onset of autoimmune diseases is a matter of debate and most of the studies are inconclusive. , Putative mechanisms should include molecular mimicry or bystander activation of dormant autoreactive T-helper cells for both tissue-specific and systemic reactions. , It is also debated whether vaccines may be the causative agent of autoimmunity or whether they rather represent the trigger of a latent autoimmunity that would have occurred later in any case. , Moreover, a period of time as short as 6 days from vaccine administration to the development of symptoms seems frankly poorly consistent with the time course of the putatively involved immunopathologic reaction, as indeed the same authors recognize.

Conversely, autoimmune diseases are rather commonly observed to present in the postpartum period, , particularly tyroiditis and rheumatoid arthritis. Nevertheless several cases of autoimmune hepatitis (AIH) have also been reported[7], [8], [9] and the addition of such a disease to the list of autoimmune conditions that may first present after pregnancy has been suggested.

Thus, we wonder whether in the case report of Bril et al., the recent pregnancy rather than the administration of the COVID-19 vaccine is the event associated with the development of AIH. In favour of such a hypothesis also stands the time of latency before clinical presentation which is more consistent with pregnancy as the causative event. In fact, symptoms of postpartum AIH have been reported to occur from a few days to 1 year after delivery, usually within 4 months, , but cases with early appearance are often difficult to differentiate from non-autoimmune pregnancy-associated liver damage.

In this sense, we agree with the authors that in terms of pharmacovigilance the case can be appropriately reported as AIH as a possible expression of a vaccine-related adverse event/reaction. However, the concomitant history of a recent pregnancy represents a tremendous confounding factor.

Financial support

No financial support was obtained for this letter to the editor.

Authors’ contributions

Pier Leopoldo Capecchi: conceived and wrote the letter to the Editor. Pietro Enea Lazzerini: made critical revision of the letter to the Editor for important intellectual content. Stefano Brillanti: made critical revision of the letter to the Editor for important intellectual content.

Conflict of interest

The authors declare no conflict of interest.

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