Analysis of Liver Disease, Nuclear HBcAg, Viral Replication, and Hepatitis B Virus DNA in Liver and Serum of HBcAg Vs. Anti-HBe Positive Carriers of Hepatitis B Virus

Abstract

Nine HBeAg+ and 24 anti-HBe+ subjects with chronic hepatitis B virus (HBV) infection were studied for HBV DNA in the serum by molecular hybridization, for HBcAg in the liver by immunofluorescence, and for histologic evidence of liver disease. All HBeAg+ patients had underlying chronic liver disease (chronic persistent hepatitis, chronic active hepatitis, or cirrhosis with or without hepatocellular carcinoma), and all were found positive for both HBV DNA in the serum and HBcAg in the nucleus of hepatocytes. Of the 24 anti-HBe+ individuals, 18 had various forms of chronic liver disease. Six HBsAg+/anti-HBe+ patients had normal liver histology except for numerous "ground-glass" hepatocytes with abundant cytoplasmic HBsAg. All six were negative for nuclear HBcAg and serum HBV DNA, but three showed HBV DNA which appeared to be integrated into unique sites in host liver DNA by hybridization analysis. In contrast, 14/18 (78%) of HBsAg+/anti-HBe' patients with chronic liver disease were positive for nuclear HBcAg, serum HBV DNA, or both of these markers of HBV replication. It is suggested that in long-term HBsAg carriers with serum anti-HBe and normal liver histology, viral replication is suppressed or inactive and HBV potential infectivity is presumably very low or absent. However, when viral replication is present in HBsAg+/anti-HBe+ carriers (as demonstrated by serum HBV DNA and/or nuclear HBcAg) active liver disease is often found. In these individuals, active chronic liver disease appears to be related to continued replication and secretion of HBV and may occur in a much higher proportion of HBsAg+/anti-HBe+ carriers than was previously suspected.It is generally accepted that in chronic hepatitis B virus (HBV) infection, the presence of circulating antibodies to HBe antigen (anti-HBe) reflects a state of low or absent HBV replication and presumably of low HBV infectivity (1-3). However, a significant number of antiHBe+ patients with chronic HBV infection have been found recently to have demonstrable HBcAg in many hepatocytic nuclei (Hadziyannis, S. J. et al., Hepatology 1982; 2:179, Abstract). Similarly, HBV DNA sequences

Associations of Expressions of HBcAg and HBsAg with the Histologic Activity of Liver Disease and Viral Replication

“…This classification of HBcAg within the hepatocytes is associated with the degree of inflammatory responses, the severity of liver cell damage and the expression of HBeAg. 5,6 In addition, HBsAg is histologically identified as cHBsAg (cytoplasmic expression), mHBsAg (membranous expression). It is known to be related to the activity of viral replication.…”

Molecular Mechanisms Underlying Occult Hepatitis B Virus Infection

“…The presence of HBeAg correlates strongly with HBV DNA levels and an aggressive course of liver disease in chronic HBV infection (105). The loss of HBeAg in chronic HBV carriers generally represents a late phase in the course of chronic HBV infection (89).…”

Histórico das hepatites virais

“…Depois de um determinado período, foram observadas (microscopia eletrônica) nas fezes dos chimpanzés partículas similares ao tamanho e morfologia 32 , daquelas encontradas por Feinstone, em 1973 22 .…”

“…Em 1972, foi descrito um novo antígeno distinto do HBsAg, sendo denominado de antígeno e do vírus da hepatite B (HBeAg), como também seu anticorpo correspondente (antiHBe) 31 . A presença sérica do HBeAg entre portadores do VHB foi identificada como um marcador de replicação viral e de alta infectividade com o HBV-DNA 32 .…”