Hepatitis B infection: current concepts and future challenges

Abstract

Chronic hepatitis B (CHB) is a global health problem affecting more than 350 million people worldwide. Chronic carriage of HBV is related to the age when the infection occurs; the younger the age the higher the chronicity rate. Knowledge of the natural history of CHB is important for the management of the disease. The goal of hepatitis B treatment is to prevent cirrhosis, liver decompensation and hepatocellular carcinoma. In clinical practice, treatment response is determined by the suppression of serum HBV DNA levels. However, current antiviral therapies are usually unable to achieve sustained off-treatment responses and eradicate the infection. Impairment of immune responses including defective innate non-cytolytic antiviral function together with exhausted T cells and the tolerogenic liver environment may all contribute to the poor clinical response. A more comprehensive understanding of the immunological phases of CHB, potential triggers of liver flares and molecular mechanisms underlying viral persistence and immunopathology will help to tailor future therapeutic strategies. A synergistic approach of boosting the immune response of the host by specific immunotherapeutic interventions and effective viral load suppression will be needed to promote sustained viral clearance in chronic infection.

Figure 1

Chronic HBV infection is characterized by a number of T-cell defects leading to viral persistence. HBV-specific T cells are tolerized or deleted in the HBV-infected liver. The aim of immunotherapeutic manipulation is to target selected pathways restoring T-cell antiviral function and recovering successful immunity.