Activation of bystander CD8⁺ T cells in a pediatric patient with acute hepatitis E

Most children with acute hepatitis A virus (HAV) or hepatitis E virus (HEV) infection are asymptomatic. Bystander CD8⁺ T-cell activation has garnered attention owing to its possible pathophysiological role in adult hepatitis. However, no reports have studied it in pediatric hepatitis. Herein, we describe the case of a three-year-old girl with acute hepatitis by HEV genotype 1. She had a history of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections, and HEV hepatitis occurred shortly after asymptomatic HAV infection. Peripheral immunophenotyping revealed activation of non-HEV-specific CD8⁺ T cells which include EBV-specific and CMV-specific CD8⁺ T cells, during the acute phase. While alanine-aminotransferase levels declined after admission, the total number of activated CD8⁺ T cells increased for four days after admission and decreased thereafter. In contrast, activation of EBV-specific and CMV-specific CD8⁺ T cells was almost at the maximal level at the time of admission, which suggest development of activated bystander CD8⁺ T cells in the early stage. This case highlights the significance of the bystander CD8⁺ T-cell activation even in pediatric hepatitis and the size of the CD8⁺ T cell memory pool in the individuals for the development of hepatitis, given the patient's history of infections with EBV, CMV and HAV.