APASL Session on Feb. 16th, 2009 Immunology in Viral Hepatitis

Qin Ning  Tongji Hospital of Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China

In this session, several issues focusingon immunology in viral hepatitis were included: an update of HBV vaccine, from the innate to adaptive immune response and the characteristics of hepatitis B virus quasispecies and its clinical significances.  

The first topic refers to an update on HBV vaccine by Prof.Mei-Hwei Chang (National Taiwan University Hospital, Taipei, Taiwan). A universal HBV vaccination program during infancy has effectively reduced the total and chronic infection rates of HBV in the vaccinated individuals. Vaccine failure, no vaccination program, and poor compliance are the main problems hindering the success of HBV prevention by vaccination. Universal HBV vaccination in infancy has produced adequate protection up to 20 years of age from the long-term data in Taiwan.

Prof. Fusheng Wang's (Beijing 302 Hospital, Beijing, China) talk is about the influence of HBV-specific CTLs on outcome of HBV infection in Human. HBV-specific CD8+T cell responses are thought to be of considerable importance in viral control and immune-mediated liver damage. During acute HBV infection, virus-specific CD8+T cell responses are generally weak, and can become exhausted during chronic HBV infection. The cellular and molecular mechanisms responsible for the HBV-specific T cell hypo-responsiveness are probably due to the following factors: negative selection, immunological ignorance, peripheral anergy, dysregulation of lymphokine production and persistent exposure to high viral Ags in hosts. In addition, dendritic cell dysfunction, increased regulatory T cells and inhibitory PD-1/PD-L1 pathway in chronic HBV infection has been proposed to impair viral specific CTLs.

The next topic is innate immune response in HBV infection by Prof. Stephen A. Locarnini(WHO Collaborating Centre for Virus Reference and Research, Melbourne, Victoria, Australia). HBV has developed a number of strategies to ensure its persistence in the infected host, including the production of excess HBsAg and the expression of HBeAg. The liver damage of chronic hepatitis B is the result of the host's cellular immune response to HBV-infected hepatocytes. Both the innate and adaptive host immune response need to be considered as a coordinated and dynamic line of attack. The roles for many components of the innate immune system have been identified, particularly the important interactions between HBeAg, HBV and Toll-like receptors (TLR-2), Kupffer cells, natural killer T-cells, and dendritic cells. Achieving clearance of HBV appears to require initial viral suppression and recruitment of effector cells by the innate immune system, along with adequate antigen presentation to and activation of the adaptive immune response arm.

The last topic by Prof. Xinxin Zhang (Ruijin Hospital, Jiaotong University School of Medicine, Shanghai, China) is a discussion about an investigation on the characteristics of hepatitis B virus quasispecies and its clinical significances. The dynamic changes of HBV quasispecies within RT region showed distinct patterns between responders and non-responders during lamivudine treatment in the early stage. The HBV quasispecies drifted rapidly to a more simple population with less mutation in responders, whereas they evolved slowly to a more complex population prone to mutation in non-responders. The quasispecies complexity and diversity at week 4 might act as a predictor for short term antiviral efficacy during lamivudine treatment.