Systemic T-cell activation and interferon-γ activity in indeterminate severe hepatitis (iSH) are reminiscent of hemophagocytic lymphohistiocytosis (HLH): Implications for T-cell and interferon-γ directed therapies.

Severe hepatitis cases in children are increasingly recognized, however, the exact etiology remains unknown in a significant proportion of patients. Cases of indeterminate severe hepatitis (iSH) may progress to indeterminate pediatric acute liver failure (iPALF), hence understanding the immunobiology is critical to preventing disease progression. Hemophagocytic lymphohistiocytosis (HLH) is a systemic hyperinflammatory disorder associated with T-cell and macrophage activation with liver injury.