Vigorous response of cytotoxic T lymphocytes associated with systemic activation of CD8+ T lymphocytes in fulminant hepatitis B

Background: Fulminant hepatitis is a clinical syndrome characterized by sudden and severe liver dysfunction. Methods: We analyzed two patients with a superacute form of fulminant hepatitis B and compared findings with those of four patients with acute self-limited hepatitis B, two patients with acute exacerbation of chronic hepatitis B and four healthy individuals. Results: In fulminant hepatitis, an increased population of human leukocyte antigen (HLA)-DR+ CD8(+) lymphocytes was observed in peripheral blood by flow cytometry, which was accompanied by the presence of HLA-DRhi lymphocytes. The phenotype of CD8(+) T lymphocytes from patients with fulminant hepatitis was mostly that of the effector T lymphocytes in peripheral blood, whereas lymphocytes with CD45RA(-) CCR7(-) phenotype dominated in the liver of these patients. A larger population of hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) appeared in peripheral circulation of the fulminant hepatitis patients compared with that in a patient with acute hepatitis. HBV-specific CTLs were highly concentrated in the liver, although epitopes recognized by these CTLs in the peripheral blood and in the liver were similar. Peripheral CTLs were mostly functional as indicated by intracellular perforin and interferon-gamma. Conclusions: These results suggest the presence of vigorous activation of CD8(+) T cells in vivo in fulminant hepatitis and the necessity of extensive therapy in patients with this disease.