Effects of Hepatitis B Surface Antigen on Virus-specific and Global T Cells in Patients With Chronic HBV infection

Abstract Background & Aims Chronic hepatitis B virus (HBV) infection is characterized by the presence of defective viral envelope proteins (hepatitis B surface antigen, HBsAg) and the duration of infection—most patients acquire the infection at birth or during the first years of life. We investigated the effects of these factors on patients’ lymphocyte and HBV-specific T-cell populations. Methods We collected blood samples and clinical data from 243 patients with HBV infection (3–75 years old) in the United Kingdom and China. We measured levels of HBV DNA, HBsAg, HBeAg, and alanine aminotransferase; analyzed HBV genotypes; and isolated peripheral blood mononuclear cells (PBMC). In PBMC from 48 patients with varying levels of serum HBsAg, we measured 40 markers on nature killer (NK) and T cells by mass cytometry. PBMC from 189 patients with chronic infection and 38 patients with resolved infections were incubated with HBV peptide libraries, and HBV-specific T cells were identified by interferon gamma ELISpot assays or flow cytometry. We used multivariate linear regression and performed variable selection using Akaike's information criterion to identify covariates associated with HBV-specific responses of T cells. Results Although T and NK cell phenotypes and functions did not change with level of serum HBsAg, numbers of HBs-specific T cells correlated with serum levels of HBsAg (r=0.3367; P Conclusions In an analysis of immune cells from patients with chronic HBV infection, we found the duration of HBsAg exposure, rather than quantity of HBsAg, associates with the level of anti-HBV immune response. Although the presence of HBs-specific T cells might not be required for clearance of HBV infection in all patients, strategies to restore anti-HBV immune responses should consider patients younger than 30 years.