[The impact of antiviral therapy on virus-specific T-cell reactivity in patients with chronic hepatitis B].

Objective: To investigated the impact of viral load decline on virus-specific T-cell reactivity on patients with chronic hepatitis B.

Methods: 23 cases of patients with chronic hepatitis B were recruited randomized to therapy with nucleoside analogue or alpha interferon from January 2009 to April 2010. Peripheral blood mononuclear cells (PBMCs) were collected longitudinally at baseline and the time of HBV DNA undetected. T-cell reactivity to HBV core antigens were tested using Elispot assays and Luminex.

Results: (1) The frequency of T cell reactivity induced by HBcAg in patients with chronic hepatitis B were 91.3% at the time of HBV DNA undetected, which significantly higher than The frequency of 69.6% at baseline. The frequency between nucleoside analogue treatment group and alpha interferon treatment group was no significant difference. (2) The average response magnitude was expressed as spot forming unit (SFU) per million input cells. SFU of T cell responses to HBcAg was 120 SFU/10(6) PBMCs at baseline, much lower than SFU of 1060 SFU/10(6) PBMCs at the time of HBV DNA undetected. No significant difference between patients with negative T cell reactivity at baseline and patients with positive T cell reactivity at baseline was found. In patients with initial virological response (IVR) to therapy and patients with early virological response (EVR), no significant difference was found in the magnitude at baseline as well as at the time of HBV DNA undetected. (3) The average response magnitude of nucleoside analogue treatment group was 1713 SFU/10(6) PBMCs at the time the time of HBV DNA undetected, higher than 189 SFU/10(6) PBMCs at baseline. But in interferon treatment group, the average response magnitude was no significant difference, 120 SFU/10(6) PBMCs at the baseline and 305 SFU/10(6) PBMCs at the time the time of HBV DNA undetected respectively. The average response magnitude in nucleoside analogue treatment group was greater than that in interferon treatment group. (4) As to compare difference of IFN-γ concentration in supernatant of T cell culture solution stimulated by HBcAg, IFN-γ secreted by T cell at the time of HBV DNA undetected was clearly higher than IFN-γ secreted at baseline, (38 ± 9) ng/L and (90 ± 9) ng/L respectively.

Conclusions: Antiviral therapy made profit to improve virus-specific T-cell reactivity in patients with chronic hepatitis B, suggesting the importance to investigate HBV specific T cell responses.