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

Abstract

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