Tehran University of Medical Sciences Immunology and Genetics Journal 2645-4831 7 3 2024 09 22 166 187 Rad Ghannadzadeh Kermani Pour Universal Scientific Education and Research Network (USERN), Tehran, Iran Pouya Mahdavi Sharif Universal Scientific Education and Research Network (USERN), Tehran, Iran 2025 02 16 2025 02 16 Mass vaccination against COVID-19 infection has been able to substantially alleviate the consequent mortalities and the spread of the disease. The paced design and administration of novel mRNA-based vaccines paved the way for the production against cancers and acquired immunodeficiency syndrome. Various side effects, lethal in some instances, are described for COVID-19 vaccines, including the instigation of incidence or relapse of autoimmune disorders, including autoimmune hepatitis (AIH). Molecular mimicry with the spike protein S1 and cross-reactions, adjuvants-induced autoimmune/autoinflammatory syndrome, epitope spreading, and bystander activation are among the molecular mechanisms that are hypothesized to mediate vaccine-induced autoimmunity. Pathological and serologic evaluations of patients with liver injury following COVID-19 vaccination have displayed that most cases can be categorized as probable or definite for the diagnosis of AIH. AIH and AIH-like liver injuries following COVID-19 vaccination are generally manageable with the administration of corticosteroids and other immunosuppressive therapies if required. Data on the safety of subsequent vaccination is scarce; however, vaccination during maintenance therapy with steroids seems safe. More importantly, the recognition of asymptomatic cases with altered liver aminotransferase levels necessitates the design of prospective cohorts to assess the long-term consequences of sub-clinical liver dysfunction induced by COVID-19 vaccines. https://igj.tums.ac.ir/index.php/igj/article/view/182 https://igj.tums.ac.ir/index.php/igj/article/download/182/154