Humoral immunity in hepatitis B virus infection: Rehabilitating the B in HBV

Abstract

Summary Insights into the immunopathogenesis of chronic HBV infections are fundamental in the quest for novel treatment approaches aimed at a functional cure. While much is known about the ineffective HBV-specific T-cell responses that characterise persistent HBV replication, B cells have been left largely understudied. However, an important role for humoral immunity during the natural history of HBV infections, as well as after functional cure, has been inadvertently revealed by the occurrence of HBV flares following B cell-depleting treatments. Herein, we review our current understanding of the role of the humoral immune response in chronic HBV, both at the level of HBV-specific antibody production and at the phenotypic and broader functional level of B cells. The recent development of fluorescently labelled HBV proteins has given us unprecedented insights into the phenotype and function of HBsAg- and HBcAg-specific B cells. This should fuel novel research into the mechanisms behind dysfunctional HBsAg-specific and fluctuating, possibly pathogenic, HBcAg-specific B-cell responses in chronic HBV. Finally, novel immunomodulatory treatments that partly target B cells are currently in clinical development, but a detailed assessment of their impact on HBV-specific B-cell responses is lacking. We plead for a rehabilitation of B-cell studies related to both the natural history of HBV and treatment development programmes.

Incidence of Hepatic Decompensation After Nucleos(t)ide Analog Withdrawal: Results From a Large, International, Multiethnic Cohort of Patients With Chronic Hepatitis B (RETRACT-B Study)

“…There are 3 major guidelines that have prespecified stopping criteria to ensure patient safety after NA withdrawal; however, these tend to vary by geographical region and local reimbursement policies (6)(7)(8)(9). Because hepatitis B e antigen (HBeAg) seroconversion comes with increased immune control, the HBeAg status also plays an important role in assessing patient eligibility for treatment cessation (10).…”

CXCL10 and its receptor in patients with chronic hepatitis B and their ability to predict HBeAg seroconversion during antiviral treatment with TDF

“…When the liver becomes inflamed due to HBV infection, a large number of chemokines such as CXCL10 and CXCL11 are produced, which can increase during local viral infection and produce directional migration signals. They play a chemotactic role for various inflammatory cells in the circulation and cause them to selectively migrate to specific sites via vascular endothelial cells to exert an antiviral effect 2,28 . So that, the high expression of CXCL10 protein in liver tissue suggests a more effective antiviral effect, such as in the present study, where immunohistochemical results showed that CXCL10/CXCR3 protein levels in the liver were significantly higher than the protein levels of HBeAg patients with antiviral treatment after 96 weeks, but the change in CXCL10/CXCR3 had no significance in HBeAg non‐SC patients.…”

Modification of clinical indicators for differentiating stages of chronic HBV infection based on pathological changes in liver tissue

“…HBcAb is the earliest antibody produced after patients are infected with HBV, which is an important marker of hepatitis B infection. However, it is not a protective antibody [34]. Song et al [35] found that the quantitative serum levels of HBcAb in chronic HBV-infected patients were closely correlated with hepatitis activity.…”