IsHDVaCytopathic Virus

The existence of a cytotoxic immune response to HDV has been assumed, as HDV itself is probably not directly cytopathic. Mice made transgenic for both small and large HDAg and expressing these proteins in the liver do not develop any form of liver disease. Hence, the hepatitis in humans may be induced rather by the immune response than by HDV itself (Guilhot et al. 1994).

The issue of the cytotoxicity of HDV itself has been investigated in different in vitro systems and yielded conflicting results. More recently, Wang et al. studied this issue extensively (Wang et al. 2001). When cells transfected with replication-competent HDV-cDNA were followed, a progressive decline in viral RNA replication and a steady decrease in the cells expressing HDAg were found. However, in transient transfection assays, no evidence was found to link HDV replication to apoptosis or cell cycle arrest. Thus, HDV does not appear to be acutely cytotoxic. In dividing cells, however, HDV replication was associated with a slight growth disadvantage. The authors discuss that this may not cause hepatitis in vivo but might contribute to impaired liver regeneration in the setting of ongoing hepatocellular injury.

In short, liver injury caused by HDV infection may be mediated both by the immune system and the virus itself.

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