Rapid downregulation of programmed death-1 and interferon-γ-inducible protein-10 expression is associated with favourable outcome during antiviral treatment of chronic hepatitis B

J Viral Hepat. 2013 Apr:20 Suppl 1:18-26. doi: 10.1111/jvh.12060.

Abstract

The dynamics of programmed death-1 (PD-1) as well as cytokine/chemokine expression and its correlation with virological response in patients with chronic hepatitis B (CHB) is unclear. This study was conducted in 29 treatment-naïve patients undergoing telbivudine treatment for 52 weeks. The results showed that PD-1 expression on both CD4+ and CD8+ T cells was positively correlated with hepatitis B virus (HBV) DNA levels (r = 0.621, P < 0.0001; r = 0.548, P = 0.002, respectively), and in virological responders, this decrease was directly correlated with a decrease in HBV DNA levels (r = 0.664, P = 0.002; r = 0.572, P = 0.01, respectively). Furthermore, at the end of 52 weeks, in virological responders, the decreased rate in the frequency of PD-1+ CD8+ T cells was significantly higher than in non-virological responders (58.3% vs 25.7%, P = 0.001), and at weeks 24 and 52, in virological responders, PD-1 expression on CD4+ and CD8+ T cells was lower than in non-virological responders (P = 0.01 and P = 0.035; P < 0.0001 and P < 0.0001, respectively). In 34 cytokines/chemokines detected in serum, IP-10 expression was positively correlated with viral load, level of ALT and PD-1 expression on CD8+ and CD4+ T cells at baseline (r = 0.36, P = 0.055, r = 0.635, P < 0.0001, r = 0.414, P = 0.026, and r = 0.402, P = 0.030, respectively). Moreover, the decrease in IP-10 in serum directly correlated with a decrease in ALT levels (r = 0.751, P < 0.0001). At weeks 24 and 25, IP-10 expression was significantly lower than baseline in virological responders (both P = 0.005); however, this was not observed in nonresponders. Based on the above findings, PD-1 and IP-10 may be used as predictors for virological response, and blockade of their pathway may improve the outcome of patients with CHB.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / metabolism*
  • China
  • Cytokines / genetics
  • Cytokines / metabolism
  • DNA, Viral / blood
  • DNA, Viral / genetics
  • Down-Regulation*
  • Female
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / physiopathology
  • Hepatitis B, Chronic / virology
  • Humans
  • Interferon-gamma / immunology*
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism*
  • Telbivudine
  • Thymidine / analogs & derivatives*
  • Thymidine / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • Antiviral Agents
  • CXCL10 protein, human
  • Chemokine CXCL10
  • Cytokines
  • DNA, Viral
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Telbivudine
  • Interferon-gamma
  • Thymidine