Restoration of T cell function in chronic hepatitis B patients upon treatment with interferon based combination therapy

Background & Aims: Chronic hepatitis B virus (HBV) infection is characterized by functional impairment of HBV-specific T cells. Understanding the mechanisms behind T cell dysfunction and restoration is important for the development of optimal treatment strategies. Methods: In this study we have first analysed the phenotype and function of HBV-specific T cells in patients with low viral load (HBV DNA < 20,000 IU/ml) and spontaneous control over the virus. Subsequently, we assessed HBV-specific T cells in patients with high viral load (HBV DNA > 17,182 IU/ml) treated with peginterferon/adefovir combination therapy who had various treatment outcomes. Results: HBV-specific T cells could be detected directly ex vivo in 7/22 patients with low viral load. These showed an early differentiated memory phenotype with reduced ability to produce IL-2 and cytotoxic molecules such as granzyme B and perforin, but with strong proliferative potential. In a cohort of 28 chronic hepatitis B patients with high viral load treated with peginterferon and adefovir, HBV-specific T cells could not be detected directly ex vivo. However, HBV-specific T cells could be selectively expanded in vitro in patients with therapy-induced HBsAg clearance (HBsAg loss n = 7), but not in patients without HBsAg clearance (n = 21). Further analysis of HBV-specific T cell function with peptide pools showed broad and efficient antiviral responses after therapy. Conclusions: Our results show that peginterferon based combination therapy can induce HBV-specific T cell restoration. These findings may help to develop novel therapeutic strategies to reconstitute antiviral functions and enhance viral clearance. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.