Adaptive immune responses during acute uncomplicated and fulminant hepatitis E

Abstract

Background and Aim: Hepatitis E virus (HEV) infection is endemic in several developing countries. Clinical manifestations of this infection vary widely from asymptomatic infection to uncomplicated acute viral hepatitis and fulminant hepatic failure. Pathogenesis of this disease and the reason of varying disease severity remain unknown. In viral infections, tissue injury can be caused either by virus itself or by host immune response directed against infected cells. We therefore studied adaptive immune responses to HEV antigens in patients with hepatitis E of varying disease severity and healthy controls. Methods: Cytokine secreting CD4+ T cells and antibody producing B cells specific for HEV were enumerated through intracellular cytokine staining and enzyme-linked immunosorbent spot assay respectively. Results: Patients with fulminant hepatitis E had less marked expansion of HEV-specific interferon-gamma or tumor necrosis factor-alpha secreting CD4 + T cells than patients with uncomplicated hepatitis E and healthy controls. These patients also had fewer CD4 + T cells that produce interferon-gamma or tumor necrosis factor-alpha on in vitro polyclonal stimulation. In addition, patients with fulminant disease had a more marked expansion of B cells that can secrete IgG anti-HEV than patients with uncomplicated infection and control subjects. Conclusion: These findings suggest that less marked anti-viral cellular immune responses and heightened anti-viral humoral responses are associated with a worse clinical outcome of HEV infection.