TY - JOUR
T1 - Restoration of T cell function in chronic hepatitis B patients upon treatment with interferon based combination therapy
AU - de Niet, Annikki
AU - Stelma, Femke
AU - Jansen, Louis
AU - Sinnige, Marjan J.
AU - Remmerswaal, Ester B. M.
AU - Takkenberg, R. Bart
AU - Kootstra, Neeltje A.
AU - Reesink, Hendrik W.
AU - van Lier, Rene A. W.
AU - van Leeuwen, Ester M. M.
PY - 2016
Y1 - 2016
N2 - 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. In this study we have first analysed the phenotype and function of HBV-specific T cells in patients with low viral load (HBV DNA <20,000IU/ml) and spontaneous control over the virus. Subsequently, we assessed HBV-specific T cells in patients with high viral load (HBV DNA >17,182IU/ml) treated with peginterferon/adefovir combination therapy who had various treatment outcomes. 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. 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
AB - 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. In this study we have first analysed the phenotype and function of HBV-specific T cells in patients with low viral load (HBV DNA <20,000IU/ml) and spontaneous control over the virus. Subsequently, we assessed HBV-specific T cells in patients with high viral load (HBV DNA >17,182IU/ml) treated with peginterferon/adefovir combination therapy who had various treatment outcomes. 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. 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
U2 - https://doi.org/10.1016/j.jhep.2015.10.013
DO - https://doi.org/10.1016/j.jhep.2015.10.013
M3 - Article
C2 - 26505119
SN - 0168-8278
VL - 64
SP - 539
EP - 546
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 3
ER -