Abstract
Natural killer (NK) cells play a critical role in innate antiviral immunity, but little is known about the impact of antiviral therapy on the frequency of NK cell subsets. To this aim, we performed this longitudinal study to examine the dynamic changes of the frequency of different subsets of NK cells in CHB patients after initiation of tenofovir or adefovir therapy. We found that NK cell numbers and subset distribution differ between CHB patients and normal subjects; furthermore, the association was found between ALT level and CD158b+ NK cell in HBV patients. In tenofovir group, the frequency of NK cells increased during the treatment accompanied by downregulated expression of NKG2A and KIR2DL3. In adefovir group, NK cell numbers did not differ during the treatment, but also accompanied by downregulated expression of NKG2A and KIR2DL3. Our results demonstrate that treatment with tenofovir leads to viral load reduction, and correlated with NK cell frequencies in peripheral blood of chronic hepatitis B virus infection. In addition, treatments with both tenofovir and adefovir in chronic HBV infected patients induce a decrease of the frequency of inhibitory receptor+ NK cells, which may account for the partial restoration of the function of NK cells in peripheral blood following treatment.
Highlights
Chronic infection with hepatitis B virus (HBV) affects more than 350 million people worldwide and continues to be an important cause of morbidity and mortality [1]
We found that Natural killer (NK) cell numbers and subset distribution differ between chronic hepatitis B (CHB) patients and normal subjects, the association was found between alanine transaminase (ALT) level and CD158b+ NK cell in HBV patients
We examined the frequency of different subsets of NK cells in patients with CHB following nucleos(t)ide analogues (NUCs) antiviral therapy
Summary
Chronic infection with hepatitis B virus (HBV) affects more than 350 million people worldwide and continues to be an important cause of morbidity and mortality [1]. It has recently shown that inhibition of chronic hepatitis B virus replication by antiviral therapeutic medicine such as entecavir, lamivudine, and adefovir helps to partially restore function of NK cells in peripheral blood [32, 33] This restoration of NK cell activity was accompanied by an enhanced frequency of IFN-γ-producing CD56+ NK cells in blood as well as normalization of the expression of the activating receptor NKG2A on circulating NK cells. Controlling of viral replication by antiviral treatment can partially correct this defect but little is known about the impact of antiviral therapy on the frequency of different subsets of NK cells To this aim, we performed this longitudinal study to examine the dynamic changes of the frequency of different subsets of NK cells in CHB patients after initiation of tenofovir or adefovir therapy. In CHB patients treatment with adefovir, NK cell numbers did not differ during the treatment, and accompanied downregulated expression of NKG2A and KIR2DL3
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