Reply to: “Comment on “Autoimmune hepatitis developing after coronavirus disease 2019 (COVID-19) vaccine: Causality or casualty?””
Authors: Fernando Bril, David M. Fettig
Journal: Journal of Hepatology (2021)

Comment on "Autoimmune hepatitis developing after coronavirus disease 2019 (COVID-19) vaccine: Causality or casualty?"Journal of HepatologyVol. 75Issue 4PreviewWe read with great interest the article by Bril F. et al. recently published in the Journal of Hepatology.1 In our opinion, several considerations increase the possibility that the described association is indeed coincidental, as also acknowledged by the authors. Full-Text PDF Autoimmune hepatitis developing after coronavirus disease 2019 (COVID-19) vaccine: Causality or casualty?Journal of HepatologyVol. 75Issue 1PreviewSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with the development of autoimmune processes.1–4 Molecular mimicry has been suggested as a potential mechanism for these associations.1 In an in vitro study, Vojdani et al.5 showed that antibodies against the spike protein S1 of SARS-CoV-2 had high affinity against the following human tissue proteins: transglutaminase 3, transglutaminase 2, anti-extractable nuclear antigen, nuclear antigen, and myelin basic protein. Full-Text PDF We read with interest the comment by Capecchi et al.1Capecchi P.L. Lazzerini P.E. Brillanti S. Comment on "Autoimmune hepatitis developing after coronavirus disease 2019 (COVID-19) Vaccine: causality or casualty?ˮ.J Hepatol. 2021; 75: 994-995Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar regarding our Letter to the Editor describing a case of autoimmune hepatitis (AIH) developing after COVID-19 vaccination.2Bril F. Al Diffalha S. Dean M. Fettig D.M. Autoimmune hepatitis developing after coronavirus disease 2019 (COVID-19) vaccine: causality or casualty?.J Hepatol. 2021 Jul; 75: 222-224Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar We thank the authors for their interest in our manuscript and for their thoughtful insight, which complemented our report. As we carefully expressed in our original letter, and Capecchi et al. further reinforced, a causal relationship between the vaccine and the development of AIH cannot be proven. Other factors, such as the postpartum status, could have acted as confounding factors. Another possibility is that the vaccine unmasked a process that was already developing. Yet, while we recognized that the temporal association could have been coincidental, we felt compelled to report this case for several reasons. There is already significant evidence supporting a strong link between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the development of autoimmunity.3Halpert G. Shoenfeld Y. SARS-CoV-2, the autoimmune virus.Autoimmun Rev. 2020; 19: 102695Crossref PubMed Scopus (128) Google Scholar Among 45 consecutive patients admitted with SARS-CoV-2 pneumonia, 35.6% were found to have positive antinuclear antibodies.4Gazzaruso C. Carlo Stella N. Mariani G. Nai C. Coppola A. Naldani D. et al.High prevalence of antinuclear antibodies and lupus anticoagulant in patients hospitalized for SARS-CoV2 pneumonia.Clin Rheumatol. 2020; 39: 2095-2097Crossref PubMed Scopus (72) Google Scholar As the spike protein believed to be responsible for autoimmunity is the same used in vaccines, there is physiological feasibility for an association between COVID-19 vaccines and autoimmune conditions. In support of this, cases of immune thrombocytopenia,5Lee E.J. Cines D.B. Gernsheimer T. Kessler C. Michel M. Tarantino M.D. et al.Thrombocytopenia following Pfizer and Moderna SARS-CoV-2 vaccination.Am J Hematol. 2021 May 1; 96: 534-537Crossref PubMed Scopus (298) Google Scholar acquired hemophilia A6Franchini M. Glingani C. De Donno G. Casari S. Caruso B. Terenziani I. et al.The first case of acquired hemophilia A associated with SARS-CoV-2 infection.Am J Hematol. 2020; 95: E197-E198Crossref PubMed Scopus (46) Google Scholar and other autoimmune processes have been reported days after COVID-19 vaccination. Unfortunately, the proportion of vaccine-related adverse events reported to the Vaccine Adverse Event Reporting System (VAERS) is likely low. Therefore, there is an urgent need to share potential adverse events to increase awareness among patients and physicians, and to encourage them to report them to the appropriate authorities. Only a large and comprehensive pharmacovigilance effort will help us answer the question as to whether these vaccines can induce autoimmunity or not. Since the publication of our letter, we have been approached by at least 4 patients throughout United States via email claiming that they have been diagnosed with autoimmune hepatitis after COVID-19 vaccination. Moreover, a quick glimpse at the 2021 VAERS database (available online at https://vaers.hhs.gov/data/datasets.html) describes several cases consistent with acute liver injury and even an AIH flare. While we do not have any further information and we understand that these cases are only anecdotal at this time, it further strengthens the importance of sharing information and experiences, in order to advance our understanding of SARS-CoV-2 infection and develop better strategies to contain the virus. Finally, and most importantly, while we ratify that it is important to further explore the potential link between COVID-19 vaccines and autoimmunity, this should not discourage patients and physicians from prescribing and/or receiving these vaccines. Even if confirmed in the future, cases of vaccine-induced autoimmunity appear to be uncommon as evidenced by only a handful of reports despite massive vaccination worldwide. Furthermore, it is likely that SARS-CoV-2 infection can trigger the same autoimmune processes as its vaccines do, leaving unvaccinated people not only at risk of developing the autoimmune process, but also the other complications associated with COVID-19. The authors received no financial support to produce this manuscript. Both authors contributed equally. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. The following is the supplementary data to this article: Download .pdf (.17 MB) Help with pdf files Multimedia component 1