Natural killer (NK) cells represent the first line of defence against viral infections but, in the case of hepatitis B virus (HBV), may also be involved in liver injury. We here compared NK-cell activity of 11 patients with acute HBV infection, either HIV-positive or HIV-negative, with that of 11 healthy subjects. One of the HIV-positive patients, characterized by a severe immunodeficiency, died 3 weeks after hospitalization for HBV-related fulminant hepatitis (FH). He displayed a remarkable NK-cell cytotoxicity against both cell lines and autologous dendritic cells, whereas the NK-cell activity of the remaining patients was significantly reduced as compared with healthy individuals. Our findings suggest that NK-cell-mediated cytotoxicity could contribute to the development of HBV-related acute liver failure in HIV-positive patients with severe immunodeficiency. An immunopathological model of FH in immunocompromised patients was proposed.
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