There is limited evidence that hepatitis A virus (HAV) infection can trigger hepatic autoimmunity, but this area remains largely unexplored. This study was thus planned with the aim to compare HAV-induced autoimmune-like hepatitis (HAV-ALH) with HAV-related liver dysfunction (HAV-acute viral hepatitis or HAV-AVH) and classical autoimmune hepatitis (AIH). This was a retrospective review of 46 patients with HAV infection who underwent liver biopsy (including 17 cases of HAV-ALH: diagnosis based on histopathology), and they were compared to 46 cases of age- and gender-matched classical AIH. Overall, HAV cohort (n = 46) had higher prevalence of pruritus, higher bilirubin levels, higher proportion of cholestasis, lower IgG levels, higher seronegativity and lack of disease recurrence, while the classical AIH group had higher proportion/severity of interface hepatitis, fibrosis, necrosis and pseudorosetting (p < 0.05). In comparison to the classical HAV-AVH group, HAV-ALH group had higher AST levels, higher presence of autoantibodies, and higher prevalence of severe zone 3 perivenulitis and marked pseudorosetting on histology (p < 0.05). Also, HAV-ALH group, in comparison to the AIH group, had more pruritus (OR 7.29, p < 0.004) and more seronegativity (41% vs. 13%, p < 0.031), while duration of illness (p < 0.003), IgG (p < 0.001) levels and liver stiffness measurement (p < 0.006) were significantly higher in AIH group (versus the HAV-ALH and HAV-AVH groups). Histologically, in comparison to AIH, HAV-ALH group had significantly less interface hepatitis (OR 0.03, p < 0.001) and fibrosis (OR 0.08, p < 0.001) and significantly more cholestasis (OR 4.5, p < 0.021). HAV infection can act as a potential trigger for immune-mediated hepatic damage, akin to drug-induced autoimmune-like hepatitis. Larger multicentric studies are needed to further explore this aspect.

Hepatitis A virus (HAV) represents a global burdening infectious agent causing in the majority of cases a self-limiting acute icteric syndrome, the outcome is related to the hepatic substrate and the potential pre-existing damage, whereas a plethora of extra-hepatic manifestations has also been reported. Despite the absence of post- HAV chronicity it has been associated with an additional burden on existing chronic liver diseases. Moreover, the induced immune response and the antigenic molecular mimicry are considered as triggering factors of autoimmunity with regional and distal impact. Diseases such as autoimmune hepatitis, Guillain-Barré syndrome, rheumatoid arthritis, Still's syndrome, Henoch-Schönlein purpura, autoimmune hemolytic anemia, antiphospholipid syndrome, systematic lupus erythematosus or cryoglobulinemic vasculitis have been described in patients with HAV infection. Although the exact mechanisms remain unclear, this review aims to accumulate and clarify the pathways related to this linkage.

Autoimmune hepatitis (AIH) is a chronic liver disease with the incidence of 10 to 17 per 100,000 people in Europe. It affects people of any age, but most often occurs in the 40-60 age group. The clinical picture is varied, from asymptomatic to severe acute hepatitis or liver failure. The disease onset is probably associated with the impaired function of T lymphocytes, the development of molecular mimicry, intestinal dysbiosis, or infiltration with low density neutrophils, which, alongside autoantibodies (i.e., ANA, ASMA), implicate the formation of neutrophil extracellular traps (NETs), as a component of the disease process, and mediate the inappropriate immune response. AIH is characterized with an increased activity of aminotransferases, elevated concentration of serum immunoglobulin G, the presence of circulating autoantibodies and liver inflammation. The result of the histological examination of the liver and the presence of autoantibodies, although not pathognomonic, still remain a distinguishing feature. The diagnosis of AIH determines lifelong treatment in most patients. The treatment is implemented to prevent the development of cirrhosis and end-stage liver failure. This work focuses mainly on the etiopathogenesis and diagnosis of AIH.

Infection with hepatotropic viruses is not limited to the liver and can lead to the development of various immunological disorders (the formation of cryoglobulins, rheumatoid factor, antinuclear antibodies, autoantibodies specific for autoimmune hepatitis and primary biliary cholangitis, and others), which can manifest as glomerulonephritis, arthritis, uveitis, vasculitis (cryoglobulinemic vasculitis, polyarteritis nodosa, Henoch-Schonlein purpura, isolated cutaneous necrotizing vasculitis), and other rheumatologic disorders, and be a trigger for the subsequent development of autoimmune hepatitis and primary biliary cholangitis. A further study of the association between autoimmune liver diseases and hepatotropic virus infection would be useful to assess the results of treatment of these associated diseases with antiviral drugs. The relationship of these immune disorders and their manifestations with hepatotropic viruses is best studied for chronic hepatitis B and C. Only isolated cases of these associations are described for hepatitis A. These links are least studied, and are often controversial for hepatitis E, possibly due to their relatively rare diagnoses. Patients with uveitis, glomerulonephritis, arthritis, vasculitis, autoimmune liver diseases should be tested for biomarkers of viral hepatitis, and if present, these patients should be treated with antiviral drugs.