HBsAg level defines different clinical phenotypes of HBeAg(-) chronic HBV infection related to HBV polymerase-specific CD8 + cell response quality

• Published in: Frontiers in immunology 2024-03, Vol.15, p.1352929
• Main Authors: Peña-Asensio, Julia, Calvo-Sánchez, Henar, Miquel-Plaza, Joaquín, Sanz-de-Villalobos, Eduardo, González-Praetorius, Alejandro, Delgado-Fernandez, Alberto, Torralba, Miguel, Larrubia, Juan-Ramón
• Format: Article
• Language: English
• Subjects: Alanine Transaminase; CD8-Positive T-Lymphocytes; functional HBV-specific CD8 + T-cell response; Gene Products, pol; HBsAg; HBV eAg(-) infection gray-zone; HBV immune control; HBV inactive carrier; Hepatitis B e Antigens - genetics; Hepatitis B Surface Antigens - genetics; Hepatitis B virus - physiology; Hepatitis B, Chronic; Humans; Immunology; Inflammation; Liver Cirrhosis; liver fibrosis progression; Phenotype
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1352929

HBe-antigen(Ag)-negative chronic hepatitis B virus (HBV) infection is characterized by little liver fibrosis progression and vigorous HBV-multispecific CD8 T-cell response. To assess whether HBsAg level could discriminate different HBeAg-negative chronic HBV infection subtypes with dissimilar quality of HBV-specific CD8 T-cell response. We recruited 63 HBeAg-negative chronic HBV infection patients in which indirect markers of liver inflammation/fibrosis, portal pressure, viral load (VL), and HBV-specific CD8 cell effector function were correlated with HBsAg level. A positive linear trend between HBsAg level and APRI, liver stiffness (LS), liver transaminases, and HBV VL, and a negative correlation with platelet count were observed. Frequency of cases with HBV-specific CD8 T-cell proliferation against at least two HBV epitopes was higher in HBsAg < 1,000 IU/ml group. CD8 T-cell expansion after HBVpolymerase -specific stimulation was impaired in HBsAg > 1,000 IU/ml group, while the response against HBVcore was preserved and response against envelope was nearly abolished, regardless of HBsAg level. Cases with preserved HBVpolymerase CD8 cell response had lower LS/duration of infection and APRI/duration of infection rates. HBV-polymerase -specific CD8 T-cell proliferation intensity was negatively correlated with LS/years of infection ratio. HBsAg > 1,000 IU/ml HBeAg-negative chronic HBV infection group shows indirect data of higher degree of inflammation, liver stiffness, and fibrosis progression speed, which are related to an impaired HBV-polymerase-specific CD8 T-cell response.