HEPATITIS-A - HEPATOTROPISM AND INFLUENCE ON MYELOPOIESIS

Immunopathologic mechanisms leading to liver tissue injury in hepatiti s caused by hepatitis A virus (HAV) were studied in an autologous in v itro model. Data show virus-specific killing by liver-infiltrating T l ymphocytes in man and support the hypothesis that hepatocellular damag e as well as efficient elimination of virus-infected hepatocytes is me diated by HLA-restricted, HAV-specific CD8+ T lymphocytes. Furthermore , experimental results demonstrate that human interferon-gamma produce d by HAV-specific T cells may act as a key factor in T-cell-promoted c learance of HAV-infected hepatocytes. Besides the well-known hepatotro pism, the myelotropic properties of HAV have some important clinical i mplications. Perturbations of hematopoietic regulation, ranging from t ransient granulocytopenia to rare cases of bone marrow failure, are as sociated with HAV infection. In an attempt to elucidate the pathogenet ic mechanisms, we could show a direct suppressive effect of HAV on hum an bone marrow progenitors and a significant progressive decline in th ese cells in HAV-infected long-term bone marrow cultures.