Effects of entecavir on peripheral blood lymphocyte profiles in chronic hepatitis B patients with suboptimal responses to adefovir

Clin Exp Pharmacol Physiol. 2014 Jul;41(7):514-23. doi: 10.1111/1440-1681.12245.

Abstract

The aim of the present study was to assess the long-term impact of entecavir (ETV) on T, B and natural killer (NK) cell immunity in patients with suboptimal responses to adefovir (SRA) chronic hepatitis B (CHB). Thirty SRA CHB patients and 20 age- and gender-matched healthy controls (HC) completed at least 6 months of ETV treatment. Hepatitis B virus (HBV) DNA loads, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the frequency of different subsets of T, B and NK cells in individual subjects were measured. There were smaller numbers of CD3(-) CD56(+) and CD244(+) NK cells, CD3(+) CD8(+) T cells and cytokine-secreting CD4(+) T cells, but greater numbers of CD3(+) CD4(+) , CD4(+) CD25(+) Foxp3(+) , CD4(+) CD25(+) CD127(low) T cells and CD19(+) CD27(+) B cells, detected in SRA patients. After switching to ETV monotherapy, the levels of HBV DNA and hepatitis B s antigen, as well as hepatitis B e antigen seropositivity, decreased gradually, accompanied by decreases in ALT and AST levels. Furthermore, the number of NK, CD8(+) and cytokine-secreting CD4(+) T cells increased, whereas the number of CD4(+) , CD4(+) CD25(+) Foxp3(+) , CD4(+) CD25(+) CD127(low) T cells and CD19(+) CD27(+) B cells decreased, in SRA CHB patients. The frequency of CD4(+) interferon-γ-positive T cells was negatively associated with serum HBV DNA levels. Thus, treatment with ETV inhibits HBV replication, modulates T and NK cell immunity and improves liver function in SRA CHB patients.

Keywords: adefovir; chronic hepatitis B; entecavir; lymphocyte subgroups; rescue therapy; virological response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Antiviral Agents / therapeutic use*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / drug effects
  • Case-Control Studies
  • DNA, Viral / metabolism
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Hepatitis B virus / metabolism
  • Hepatitis B, Chronic / blood*
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Organophosphonates / therapeutic use*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Viral Load

Substances

  • Antiviral Agents
  • DNA, Viral
  • Organophosphonates
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • entecavir
  • Guanine
  • adefovir
  • Adenine