11] Emerging Infectious Diseases (EID) Program, Duke-NUS Graduate Medical School, Singapore  Viral Hepatitis Laboratory, Singapore Institute for Clinical Sciences, Agency of Science Technology and Research (A*STAR), Singapore.
2Blizard Institute, Barts and The London School of Medicine & Dentistry, London, UK.
Chronic hepatitis B virus (HBV) infection progresses through distinct disease phases that are strongly associated with patient age. The so-called immune tolerant (IT) phase represents the classical early phase of infection; it is associated with high levels of HBV replication and lack of clinical signs of liver Inflammation. Whether this phase of HBV infection is also associated with immunological features of "tolerance' has recently been challenged. Here, we review the data that dispute this concept of immune tolerance and then propose an alternative interpretation of the immunopathological events that take place during this early phase of CHB infection.