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

Seroconversion from HBeAg to alpha HBe of persons chronically infected by H BV is usually associated with a transient exacerbation of liver disease and subsequent normalization of liver histology. It is speculated that these c linicopathological features may be due to the activation of cytodestructive mechanisms by alpha HBe antibodies. The aim of the present study was to in vestigate the pathogenic potential of alpha HBe antibodies in a transgenic mouse model. Therefore, alpha HBe autoantibodies were elicited in double-tr ansgenic mice expressing high amounts of HBeAg and interferon-gamma in the liver. Interferon-gamma has previously been shown to play an important role in the development of hepatic necroinflammation associated with hepadnavir al infection, probably via tumor-necrosis-factor-or secreted by activated m acrophages. We found no evidence that alpha HBe antibodies have the potenti al to destroy HBeAg-secreting hepatocytes even if the cells were predispose d to injury due to high-level interferon-gamma expression. We conclude that seroconversion from HBeAg to alpha HBe of persons chronically infected wit h HBV seems to be an immunological epiphenomenon without pathogenic signifi cance.