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

Background & AimsChronic 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.MethodsIn 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.ResultsHBV-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.ConclusionsOur 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.

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