Department of Central Laboratory, the Second Part of the First Hospital, Jilin University, Changchun, China.
Antimicrob Agents Chemother. 2013 Mar;57(3):1304-11. doi: 10.1128/AAC.02181-12. Epub 2012 Dec 28.
Chronic infection with hepatitis B virus (HBV) is associated with impairment of T and NK cell immunity. This study was aimed at investigating the impact of treatment with telbivudine (LDT) on T and NK cell immunity in patients with chronic hepatitis B (CHB). A total of 54 CHB patients and 30 healthy controls (HC) were recruited. Individual patients were treated orally with 600 mg LDT daily for 13 months. The serum HBV DNA loads, the levels of the HBV-related biomarkers alanine aminotransferase (ALT) and aspartate transaminase (AST), and the numbers of different subsets of peripheral T and NK cells in subjects were measured before and longitudinally after LDT treatment. Following treatment with LDT, the serum HBV DNA loads and the percentages of HBsAg- or HBeAg-seropositive cases were gradually reduced, accompanied by decreased levels of serum ALT and AST. In comparison with the HC, fewer CD3(-) CD56(+) and CD244(+) NK cells and CD3(+) CD8(+) T cells, lower frequencies of cytokine(+) CD4(+) T cells, and more CD3(+) CD4(+), CD4(+) CD25(+) Foxp3(+), CD4(+) CD25(+) CD127(low), and CD8(+) PD-1(+) T cells were detected in CHB patients. Treatment with LDT increased the numbers of NK and CD8(+) cells and the frequencies of cytokine(+) CD4(+) T cells but reduced the numbers of CD4(+) CD25(+) Foxp3(+), CD4(+) CD25(+) CD127(low), and CD8(+) PD-1(+) T cells in CHB patients. The frequencies of cytokine(+) CD4(+) T cells were negatively associated with the levels of serum HBV DNA, ALT, and AST. Thus, treatment with LDT inhibits HBV replication, modulates T and NK cell immunity, and improves liver function in Chinese patients with CHB.
慢性乙型肝炎病毒(HBV)感染与 T 细胞和 NK 细胞免疫受损有关。本研究旨在探讨替比夫定(LDT)治疗对慢性乙型肝炎(CHB)患者 T 和 NK 细胞免疫的影响。共招募了 54 例 CHB 患者和 30 名健康对照者(HC)。个体患者每天口服 600mg LDT 治疗 13 个月。在 LDT 治疗前后及治疗过程中测量了受试者的血清 HBV DNA 载量、HBV 相关生物标志物丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平以及外周 T 和 NK 细胞的不同亚群数量。经 LDT 治疗后,血清 HBV DNA 载量和 HBsAg 或 HBeAg 阳性病例的比例逐渐降低,同时血清 ALT 和 AST 水平降低。与 HC 相比,CHB 患者中 CD3(-)CD56(+)和 CD244(+)NK 细胞和 CD3(+)CD8(+)T 细胞较少,细胞因子(+)CD4(+)T 细胞频率较低,CD3(+)CD4(+)、CD4(+)CD25(+)Foxp3(+)、CD4(+)CD25(+)CD127(low)和 CD8(+)PD-1(+)T 细胞较多。LDT 治疗可增加 NK 和 CD8(+)细胞数量及细胞因子(+)CD4(+)T 细胞频率,减少 CD4(+)CD25(+)Foxp3(+)、CD4(+)CD25(+)CD127(low)和 CD8(+)PD-1(+)T 细胞数量。细胞因子(+)CD4(+)T 细胞频率与血清 HBV DNA、ALT 和 AST 水平呈负相关。因此,替比夫定治疗可抑制 HBV 复制,调节 T 和 NK 细胞免疫,改善中国 CHB 患者的肝功能。