Clinico-Pathological Spectrum of Hepatitis A Virus-Induced Autoimmune-Like Hepatitis in Children

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.