Autoimmune-Like Hepatitis Related to SARS-CoV-2 Vaccination: Towards a Clearer Definition

Vaccines are the most effective tool against COVID-19 and are generally safe. Very rare and heterogeneous cases of acute liver injury associated to all types of SARS-CoV-2 vaccines have been reported, mostly with autoimmune features. Epidemiological studies used heterogeneous diagnostic criteria and included different populations. Immunological studies in selected cases of acute liver injury linked to mRNA SARS-CoV-2 vaccines suggest that it has a unique pathophysiology, the vaccine-encoded spike protein playing a central role in triggering the aberrant immune response. In most series, liver injury was observed more often following the second vaccine dose. Latency from vaccination to the diagnosis of hepatitis was 1-147 days after the last vaccine dose. Raised immunoglobulin G levels and positive anti-nuclear and/or anti-smooth muscle antibodies are frequent. The vast majority of reported cases have been treated with corticosteroids, mostly associated with azathioprine. Outcome is generally favourable, but cases requiring liver transplantation or causing death have been reported. The heterogeneous clinical entity of acute liver injury linked to SARS-CoV-2 vaccines includes patients requiring long-term immunosuppression, similarly to autoimmune hepatitis, and patients with self-limiting liver damage, possibly representing a unique form of autoimmune-like hepatitis, which we suggest being referred to as SARS-CoV-2 vaccine-associated liver injury (SVALI). Further studies are needed to investigate the pathogenic mechanisms related to the immune response to the spike viral protein in the liver.