Hepatitis B virus (HBV) infection acquired in adult life is generally self-limited while chronic persistence of the virus is the prevalent outcome when infection is acquired perinatally. Both control of infection and liver cell injury are strictly dependent upon protective immune responses, because hepatocyte damage is the price that the host must pay to get rid of intracellular virus. Resolution of acute hepatitis B is associated with functionally efficient, multispecific antiviral T-cell responses which are preceded by a poor induction of intracellular innate responses at the early stages of infection. Persistent control of infection is provided by long-lasting protective memory, which is probably sustained by continuous stimulation of the immune system by trace amounts of virus which are never totally eliminated, persisting in an occult episomic form in the nucleus of liver cells even after recovery from acute infection. Chronic virus persistence is instead characterized by a lack of protective T-cell memory maturation and by an exhaustion of HBV-specific T-cell responses. Persistent exposure of T cells to high antigen loads is a key determinant of functional T-cell impairment but also other mechanisms can contribute to T-cell inhibition, including the tolerogenic effect of the liver environment. The degree of T-cell impairment is variable and its severity is related to the level of virus replication and antigen load. The antiviral T-cell function is more efficient in patients who can control infection either partially, such as inactive HBsAg carriers with low levels of virus replication, or completely, such as patients who achieve HBsAg loss either spontaneously or after antiviral therapy. Thus, understanding the features of the immune responses associated with control of infection is needed for the successful design of novel immune modulatory therapies based on the reconstitution of efficient antiviral responses in chronic HBV patients.
Keywords: Immune modulatory therapies; Innate responses; T cell exhaustion; T cell memory; T cells.
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.