The current desirable endpoint of treatment against
chronic hepatitis B virus infection (cHBV) is to achieve a functional cure, which is defined as
HBsAg loss (sAg-L) with or without anti-HBs seroconversion. However, the immunological features that are associated with functional cure have not been studied in detail.
METHODS: 172 cHBV patients (67 HBeAg+ and 105
HBeAg-), including 141
HBsAg retained (sAg-R) patients (115
chronic hepatitis and 26 asymptomatic carriers), 31 sAg-L patients, and 24 healthy individuals (vaccinated but not infected with HBV) were examined for their T cell phenotypic profile and HBV-specific T cell responses by flow cytometry. 18 cHBV patients with low serum
HBsAg levels were also longitudinally followed for their T cell phenotypic profile and HBV-specific T cell responses up to 60 weeks.
FINDINGS: sAg-L patients showed distinct CD4+ and CD8+ T cell phenotype fingerprints compared to those of sAg-R patients, as mainly indicated by the upregulation of
HLA-DR on both CD4+ and CD8+ T cells, and a potent
HBcAg-specific CD8+ T cell response. The changes in the T cell phenotype in cHBV patients were even more profound during rapid
HBsAg decrease and was associated with
interferon α treatment. The expression of
HLA-DR (r = 0·3269, p = 0·0037), CD95 (r = 0·2796, p = 0·0151),
CD40L (r = 0·2747, p = 0·0156), CTLA-4 (r = 0·2786, p = 0·0148), TIM-3 (r = 0·3082, p = 0·0068), CD107a (r = 0·3597, p = 0·0013) on CD4+ T cells, and
HLA-DR (r = 0·3542, p = 0·0016), CD69 (r = 0·2507, p = 0·0279), CD107a (r = 0·2875, p = 0·0112) on CD8+ T cells were positively correlated with the rate of
HBsAg decrease. The expression of
HLA-DR (r = 0·2846, p = 0·0009) and CD95 (r = 0·2442, p = 0·0049) on CD8+ T cells were positively correlated with the magnitude of the
HBcAg-specific T cell responses in cHBV patients. Importantly, CTLA-4, CD95 and CD107a expression on CD4+ T cells, as well as
HLA-DR and TIM-3 expression on CD8+ T cells in combination with
HBsAg quantification were identified as potential predictive factors for sAg-L within 48 weeks in cHBV patients.
INTERPRETATION: