Hepatocytes of double-transgenic mice expressing high levels of hepatitis B virus e antigen and interferon-γ are not injured by HBeAg specific autoantibodies

Seroconversion from HBeAg to αHBe of persons chronically infected by HBV is usually associated with a transient exacerbation of liver disease and subsequent normalization of liver histology. It is speculated that these clinicopathological features may be due to the activation of cytodestructive mechanisms by αHBe antibodies. The aim of the present study was to investigate the pathogenic potential of αHBe antibodies in a transgenic mouse model. Therefore, αHBe autoantibodies were elicited in double-transgenic mice expressing high amounts of HBeAg and interferon-γ in the liver. Interferon-γ has previously been shown to play an important role in the development of hepatic necroinflammation associated with hepadnaviral infection, probably via tumor-necrosis-factor-α secreted by activated macrophages. We found no evidence that αHBe antibodies have the potential to destroy HBeAg-secreting hepatocytes even if the cells were predisposed to injury due to high-level interferon-γ expression. We conclude that seroconversion from HBeAg to αHBe of persons chronically infected with HBV seems to be an immunological epiphenomenon without pathogenic significance.