J Hepatol. 2020 Apr 22. pii: S0168-8278(20)30225-7. doi: 10.1016/j.jhep.2020.04.013. [Epub ahead of print]
Hepatitis B Surface Antigen Seroclearance: Immune Mechanisms, Clinical Impact, Importance for Drug Development.
Tout I1, Loureiro D1, Mansouri A1, Soumelis V2, Boyer N1, Asselah T3.
Author information
1
University Paris Diderot, Sorbonne Paris Cité, CRI, UMR 1149, Inserm, F-75018 Paris, France; Department of Hepatology, AP-HP Hôpital Beaujon, Clichy 92110, France.
2
Institut Curie, Centre de Recherche, PSL Research University, Paris, France; INSERM U932, Immunity and Cancer, Paris, France.
3
University Paris Diderot, Sorbonne Paris Cité, CRI, UMR 1149, Inserm, F-75018 Paris, France; Department of Hepatology, AP-HP Hôpital Beaujon, Clichy 92110, France. Electronic address: [email protected].
Abstract
Hepatitis B surface antigen (HBsAg) seroclearance occurs rarely in the natural history of chronic hepatitis B (CHB) infection and is associated with a reduced risk of hepatocellular carcinoma (HCC). Many factors are associated with HBsAg seroconversion, including immune, and viral factors. However, the immune mechanisms associated with HBsAg seroclearance are still difficult to elucidate. The aim of the treatment of hepatitis B virus (HBV) infection is the seroclearance of HBsAg. Unfortunately, this goal is rarely reached with current approved treatments. Understanding HBsAg loss mechanisms appears important to achieve an HBV cure drug development. While studies from HBV animal models are giving insights on the potential immune mechanisms and interactions occurring between the immune system and HBsAg, they do not recapitulate all features of CHB in human and are subject to variability due to their complexity. In this article, we review recent studies on these immune factors, their influence on CHB progression, and HBsAg seroconversion. These data provide new insights in the development of immune therapeutic approaches to partially restore the anti-HBV immune response. Targeting HBsAg will ideally relieve the immunosuppressive effects on the immune system and help to restore anti-HBV immune responses.