Hepatitis B : a light microscopical and immunohistochemical study

The findings reported in this thesis provide a basis for a strategy for anti-viral treatment of chronic hepatitis B. Theoretically several approaches to the treatment of a viral infection exist. Because there is strong evidence for a direct relation between viral replication and activity of the liver disease, one therapeutic possibility may be to achieve suppression of viral replication and thus amelioriation of disease activity. For this purpose drugs that interfere with both viral RNA transcription and the production of viral proteins can be administered in order to suppress replication of the virus. At present however such drugs are. not available. Moreover the infection will not be cured: instead only the effects will mitigated. Such a drug may suppress both the immune mechanism, by diminishing protein (HBsAg) production, and the toxic effects, by reducing proliferation of the virus. Elimination of the potential of an infected cell to produce a virus is another possibile approach. To accomplish this aim, drugs can be used that eliminate ali infected hepatocytes from the liver. As shown in chapter VI, in chronic hepatitis all hepatocytes appear to be infected by the virus, as demonstrated by the diffuse cell membranebound HBsAg localization, so that such a therapy would imply elimination of all hepatocytes. If this elimination were to occur rapidly, the result would be massive liver cell necrosis and death of the patient A more realistic way to eliminate the potential of infected cells to produce virus would be to cure infection of the hepatocyte. Such a therapy may be achieved by inhibition of viral DNA synthesis. Since viral DNA formation depends on reverse transcription, drugs such as phosphonoformic acid that interfere with reverse transcriptasewould prevent the generation of cccDNA. However preliminary results with this type of drug are not hopeful. A decline in viral replication activity is followed by rapid restoration of this activity after withdrawal of the drug. Finally, another possibility is to cure the chronic infection by creating a situation in which newly formed hepatocytes are protected against reinfection by the virus. In this way, the number of infected hepatocytes will slowly decrease, as a result of regeneration of the liver, and all infected cells will eventually disappear.