Immune response and tolerance during chronic hepatitis B virus infection

The hepatitis B virus (HBV) is a hepatotropic non-cytopathic DNA virus that despite the presence of an effective prophylactic vaccine is estimated to infect 300 million people, with a particularly high prevalence in Asia and Africa. It causes liver diseases that vary greatly in severity from person to person. Some subjects control infection efficiently and clear the virus from the bloodstream either without clinically evident liver disease or with an acute inflammation of the liver (acute hepatitis) that can resolve without long-term clinical sequelae. Other patients fail to clear the virus and develop chronic infection. Most chronically infected patients remain asymptomatic without life-threatening liver disease but 10–30% develop liver cirrhosis with possible progression to liver cancer. Outcome of infection and the pathogenesis of liver disease are determined by virus and host factors, which have been difficult tofully elucidate because the host range of HBV is limited to man and chimpanzees. However, the study of animal models of related Hepadnavirus infections and transgenic mouse able to express individual HBV genes or replicate the entire viral genome have clarified several aspects connected to HBV infection. Furthermore, the ability to analyze many immunological phenomena ex vivo through direct quantification of Ag-specific T cells in humans and chimps has considerably increased our knowledge of HBV pathogenesis. Here, we will discuss the distinctions of HBV adaptive immunity between resolved and persistently infected patients and the host/viral factors that can cause and maintain them.