The Role of Hepatitis B Surface Antibodies in Hbv infection, Disease and Clearance

Abstract

<jats:p> The clinical sequelae associated with chronic HBV infection is generally regarded as a consequence of an inadequate and inappropriate immune response to active viral replication, predominantly at the T-cell level. However, recent studies on hepatitis B surface antigen (HBsAg)-specific B cells and hepatitis B surface antibody (anti-HB) responses have identified their previously unrecognized role in the pathogenesis of chronic hepatitis B (CHB). These studies have also uncovered novel therapeutic approaches to more effectively target HBsAg loss and seroconversion, an important end point and regarded as a functional cure. Anti-HBs IgG has also been shown to have multiple direct acting antiviral roles with the Fab component directly blocking viral entry, and release while the Fc component has been linked to antibody dependent cellular cytotoxicity. Likewise, the HBsAg-specific B-cell dysfunctionality can be reversed providing new therapeutic opportunities to achieve functional cure in CHB. </jats:p>

Chinese Patent Medicine Liuweiwuling Tablet had Potent Inhibitory Effects on Both Wild-Type and Entecavir-Resistant Hepatitis B Virus (HBV) in vitro and Effectively Suppressed HBV Replication in Mouse Model

“…Clinical use of LWWL has shown that it is well efficacious on anti-inflammation of chronic HBV infection (Hepatobiliary Specialized Committee of China Association of Chinese Medicine et al, 2020). In addition, a meta-analysis documented that combination of LWWL with NAs (at least for 3 months) could increase the rate of HBV DNA undetectability ( OR = 1.8–6.71, p < 0.05) and HBeAg loss ( OR = 1.83–2.04, p < 0.05) compared to single use of NAs ( He et al, 2017 ; Wang et al, 2020 ). So far, there is still lack of data on experimental anti-HBV effects and underlying mechanisms of LWWL.…”

“…This antiviral effect was verified in HBV-replicating mouse. HBV antigen such as HBsAg is critical for HBV to establish immune tolerance, which could facilitate the persistence of HBV infection by suppressing host immunity through the regulation of IFN-related pathway ( Jiang et al, 2014 ; Warner et al, 2020 ). LWWL had a better efficacy in suppression HBsAg production and this endow it potential to play a synergistic effect with NAs.…”

Molecular and Serological Characterization of Hepatitis B Virus (HBV)-Positive Samples with Very Low or Undetectable Levels of HBV Surface Antigen

“…In the current study, the OBI sample group had a higher rate of anti-HBs positivity than the HSLD comparison group (41.5% vs. 3.6%), and within the OBI group anti-HBs was more prevalent in the HBsAgNx-negative samples than among the HBsAgNx positives (45.2% vs. 28.6%). Recent reports have indicated that anti-HBs may inhibit the secretion of subviral particles [36]. Whether varying degrees of immune control might lead to a continuum of HBsAg levels below the detection limits of even highly sensitive HBsAg assays is a topic for further study.…”

The Battle for Survival: The Role of RNA Non-Canonical Tails in the Virus–Host Interaction

“…Nucleotide analogues and immune modulators are widely-used antiviral agents that are effective in preventing the spread of infectious viruses, but these medicines have several disadvantages such as strong side effects and the development of drug resistance [ 65 , 66 , 67 ]. Currently, HBsAg has a major role in host immune escape and HBsAg together with HBV DNA levels are the hallmarks of chronic HBV infection, and HBsAg is the foundation for diagnosing infections, screening blood, and determining the cure for antiviral therapy [ 68 , 69 , 70 ]. So, HBsAg inhibitors have been extensively screened to overcome chronic HBV infection and they can be structurally divided into DHQ (dihydroquinazinone) and THP (tetrahydropyridine) classes [ 71 , 72 ].…”