Parallel decline of CD8+CD38+ lymphocytes and viremia in treated hepatitis B patients

World J Gastroenterol. 2011 May 7;17(17):2191-8. doi: 10.3748/wjg.v17.i17.2191.

Abstract

Aim: To assess the peripheral T lymphocyte subsets in chronic hepatitis B virus (HBV) infection, and their dynamics in response to adefovir dipivoxil monotherapy.

Methods: Proportions and absolute counts of peripheral natural killer cells, B cells, CD8+, CD4+, CD8+CD38+, CD8+CD28+ and CD4+CD28+ T cells were determined using three-color flow cytometry in chronic hepatitis B patients (n = 35), HBV carriers (n = 25) and healthy controls (n = 35). Adefovir dipivoxil was initiated in 17 chronic hepatitis B patients who were regularly followed for 72 wk, during which period the T cell subsets and serum viral load were measured at each follow-up point.

Results: The peripheral CD4+ T cell counts and CD8+ T cell counts decreased in chronic HBV infection. In chronic hepatitis B patients, proportions of CD8+CD38+ T cells were 62.0% ± 14.7%, much higher than those of HBV carriers and healthy controls. In the 13 hepatitis B patients who were treated and responded to adefovir dipivoxil, proportions of CD8+CD38+ T cells decreased from 53.9% ± 18.4% pre-therapy to 20.1% ± 11.3% by week 72 (P < 0.001), concomitant with viral load decline (HBV DNA fell from 7.31 to 3 log copies/mL). CD8+ T cell counts also underwent an average increase of 218 cells/μL by the end of 72-wk treatment. In those who failed the therapy, the CD8+CD38+ T cell population had more fluctuations.

Conclusion: CD8+ T cells abnormally activated in chronic HBV infection can be partially reversed by antiviral therapy. HBV-associated immune activation may be a crucial part of the pathogenesis and a promising target of treatment.

Keywords: CD8+CD38+; Chronic hepatitis B; Hepatitis B virus; T cell subsets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / analysis*
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • CD3 Complex / analysis*
  • Female
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / virology
  • Humans
  • Male
  • Membrane Glycoproteins / analysis*
  • Middle Aged
  • Organophosphonates / therapeutic use*
  • T-Lymphocyte Subsets / immunology*
  • Viremia / drug therapy*
  • Viremia / immunology

Substances

  • CD3 Complex
  • Membrane Glycoproteins
  • Organophosphonates
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1
  • Adenine
  • adefovir dipivoxil