key: cord-1042431-7sq6yi2q
authors: Fernando, Bril
title: Autoimmune Hepatitis Developing After Coronavirus Disease 2019 (COVID-19) Vaccine: One or Even Several Swallows Do Not Make a Summer
date: 2021-08-10
journal: J Hepatol
DOI: 10.1016/j.jhep.2021.08.001
sha: 4560540fb2e48f4d6e8868089a3d7db9d5095728
doc_id: 1042431
cord_uid: 7sq6yi2q

nan

, and Lodato et al (5) , and I appreciate their contribution. All these authors presented similar cases of autoimmune hepatitis (AIH) that developed after coronavirus disease 2019 (COVID-19) vaccine, with the exception of Lodato et al (5) , who actually described a case of acute liver injury with some features of autoimmunity.

First of all, I was glad to see the repercussions of our manuscript, as it triggered the publication of many similar cases. Only by sharing experiences we will be able to learn more about COVID-19 infection and the effects of its vaccines. Our observation was evidently not an isolated finding, and similar presentations were observed worldwide.

Capecchi et al (6) suggested that a period of time of 6 days after vaccine administration, as seen in our case (7) , seemed inconsistent with an immunopathologic reaction. However, among these 5 other cases, the latency period was similarly short and ranged from only 4 to 35 days.

With some small variations, the cases also shared similar biochemical, immunological, and histological characteristics (Table 1) . Indeed, a peculiarity among all these cases was a histology with characteristics of an immune process with features of drug-induced toxicity.

Moreover, rate and speed of improvement with glucocorticoids appeared to be similar in all the cases, and no relapses have been observed thus far. Only a longer follow-up will help us assess the risk of relapses in these cases. Further supporting a link between the vaccines and AIH, some of the authors even observed worsening of the symptoms after the second dose of the vaccine (1, 5).

However, while the resemblance of all these cases suggests a potential causality link between the vaccine and AIH, as the title of this article suggests, this cannot be taken as proof that this link really exists. Considering an annual incidence of 1 case per 100,000 habitants as previously J o u r n a l P r e -p r o o f reported (8) , and assuming an even distribution during the 12 months, we can estimate 1 monthly case per 1,200,000 habitants. Based on CDC data, during the first month of the US COVID-19 vaccination program, approximately 13,000,000 people received at least 1 dose of the vaccine (available at https://covid.cdc.gov/covid-data-tracker/#vaccinations). Based on AIH incidence, we can therefore roughly estimate that ~10 people from this vaccinated cohort would have developed AIH within a month of getting the vaccine. Thus, it should not be surprising that we will all continue to see these cases as we continue with our vaccination efforts.

Epidemiological studies assessing changes in AIH incidence may be able to shed some light on this uncertainty. Only if we observe a true increment of AIH incidence after COVID-19 vaccination, we can make the case of a potential relationship. Until then, primary care providers and hepatologists are encouraged to keep their eyes open and maximize adverse event reporting to the appropriate authorities.

In summary, we need to remain vigilant and stay open to the idea that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its vaccines may induce autoimmune processes, including AIH. However, we do not have any solid proof of a causative relationship.

And even if there was a relationship, it is probably the result of cross-reactivity to the viral spike protein (9) and likely to be much worse after COVID-19 infection than vaccination. Writing from Alabama, a US state with one of the lowest vaccination rates, I am witnessing first-hand the consequences of low vaccination rates. Therefore, it is crucial that we continue to promote widespread vaccination. Only with this strategy will we be able to ultimately defeat COVID-19. 

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