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

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.