The pathogenesis and clinical manifestations of hepatitis B infection are primarily due to the interaction of the viruses and host immune system.
Hepatitis B virus, after entering the blood, infects the hepatocytes in the liver with the expression of viral antigen on the surface of infected cells. Cytotoxic T cells, such as activated CD4 and CD8 lymphocytes, recognize various HBV-derived proteins present on the surface of hepatocytes resulting in an immunological reaction.
A chronic carrier stage with HBV infection is an important event in the pathogenesis of HBV infection. A person with chronic carrier stage has HBsAg persisting in the blood for at least 6 months. This stage is caused by a persistent infection of the hepatocytes that leads to the presence of HBV and HBsAg in the blood. This chronic carrier stage occurs in about 5% of patients with HBV infection in contrast to no chronic carrier stage in patients with HAV infection.
In an infected host whether the person will become a chronic carrier state or will be free of infection depends on the cytotoxic T-cell response. If the cytotoxic T-cell response is strong, the infection is cleared in the person but if the response is inade-quate, the person becomes a chronic carrier.
During the chronic stage, the HBV DNA is present in epi-some in the cytoplasm of persistently infected cells, and in some cells the viral DNA is integrated with cellular DNA. Chronic carrier state is more likely to occur when infection occurs in a newborn than in adult. It has been observed that approximately 90% of the infected neonates become chronic carriers.
Approximately 20% of HBsAg carriers, nearly 1% of all adult patients infected with HBV, and high percentage of neonates infected with the virus progress to develop hepatocellular carcinoma or cirrhosis. The hepatocellular carcinoma appears to be the result of persistent cellular regeneration that tends to replace the dead hepatocytes. Also it is suggested that the inte-gration of HBV DNA with hepatocytes DNA could activate a cellular oncogene, resulting in loss of control of the growth of hepatocytes. However, the HBV genome has no oncogene which can be responsible directly for causing hepatocellular carcinoma.
Hepatitis B virus natural infection induces a lifelong immunity. The immunity is primarily mediated by humoral antibodies against HBsAg. Antibodies to HBsAg are protective. These antibodies bind to surface antigens or with the virus and prevent it from interaction with receptors on the hepatocytes. These antibodies appear to neutralize the infectivity of HBV. But the antibodies against core antigen HBcAg are not protec-tive because the antibodies cannot act with HBcAg present inside the cells.