Downregulation and altered function of natural killer cells in hepatitis B virus patients treated with entecavir.

ABSTRACT

The aim of the present study was to investigate the natural killer (NK) cell phenotype and function in chronic hepatitis B virus (HBV) patients and to study the effects of entecavir therapy (10 mg/day, p.o.) on these responses. Peripheral blood NK cells were collected from 18 chronic HBV patients and 14 healthy controls. The effect of entecavir therapy on the phenotype and function of NK cells in chronic HBV patients was characterized by flow cytometry analysis. Concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), HBV viral loads in both groups and potential associations between the frequency of peripheral NK cell subsets and clinical measures were determined. There was a significant reduction in the number of CD3(-)CD56(+) NK cells in chronic HBV patients compared with healthy controls. Furthermore, there were significant increases in the percentage of CD3(-)CD56(+)NKG2D(+) and CD3(-)CD56(+)NKP30(+) NK activating receptors in chronic HBV patients compared with healthy individuals, who exhibited downregulated expression following entecavir treatment. Spearman's correlation analysis revealed that there was a significant positive correlation between the percentage of NKG2D(+) and NKP30(+) NK cells and serum ALT levels. Characterization of NK cell degranulation indicated that the frequency of CD107a(+) NK cells in HBV patients (in response to K562 stimulation) was significantly greater than in healthy controls but decreased following entecavir treatment. Entecavir treatment of hepatitis B e antigen-positive chronic HBV-infected patients not only led to a reduction in HBV DNA loads and normalization of ALT and AST levels, but also resulted in the recovery of NK cell-mediated immunity.