恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者外周血Treg/Th17平衡与HBeAg的变化

Relationship between Treg/Th17 balance and changes in HBeAg among HBeAg-positive chronic hepatitis B patients receiving entecavir therapy

目的探讨慢性乙型肝炎(chronic hepatistis B,CHB)e抗原(hepatitis B e antigen,HBeAg)阳性患者恩替卡韦治疗过程中Treg/Th17平衡与HBeAg变化的关系。方法收集HBeAg阳性CHB患者33例作为治疗组,分别检测其恩替卡韦治疗前及治疗4、8、12、16、20、24周乙肝标志物(HBeAg、HBsAg)、肝功能(ALT)、HBV-DNA载量、Treg以及Th17细胞频数。选取相同时间段13例体检健康者相同检测指标作为对照。结果恩替卡韦治疗前CHB患者外周血Treg以及Th17细胞频数均显著高于健康对照组,且Treg细胞频数与HBV-DNA载量、HBeAg以及HBsAg水平呈正相关。恩替卡韦治疗过程中Treg细胞频数呈下降趋势,Th17细胞频数改变呈倒"V"字型。治疗24周后7名CHB患者达到HBeAg转阴,HBeAg转阴组未治疗前Treg细胞频数、Treg/Th17比率均显著低于HBeAg未转阴组,且恩替卡韦治疗过程中CHB患者Treg细胞频数的改变与HBeAg水平的变化呈正相关。结论HBeAg阳性CHB患者恩替卡韦治疗前外周血较低水平的Treg细胞频数以及Treg/Th17比率更易于达到治疗后HBeAg转阴,而且治疗过程中Treg细胞频数的改变情况可能预测HBeAg是否能够转阴。

Objective To investigate the relationship between Treg/Th17 balance and HBeAg changes in HBeAg-positive chronic hepatitis B(CHB)patients receiving entecavir therapy.Methods Thirty-three HBeAg-positive CHB cases were enrolled as the treatment group.The biomarkers of hepatitis B(HBeAg,HBsAg),liver function(ALT),load of HBV-DNA,cell frequencies of Treg and Th17 before and 4,8,12,16,20 and 24 weeks after entecavir therapy were measured.Thirteen healthy volunteers were selected as control group and were tested in the same period.Results Both cell frequencies of Treg and Th17 in peripheral blood of CHB patients in treatment group before entecavir treatment were higher than those of healthy control group.The cell frequency of Treg was positively related to the load of HBV-DNA,and levels of HbeAg and HBsAg.During the treatment of entecavir,the cell frequency of Treg showed a trend of decreasing while the cell frequency of Th17 changed in a reversed"V"curve.After 24 weeks of treatment,7 patients converted to be HBeAg negative.The cell frequency of Treg and Treg/Th17 ratio among patients negative conversion of HBeAg negative were significantly lower than those of patients without conversion.The cell frequency of Treg of the patients was positively correlated to HBeAg level during the entecavir treatment.Conclusion The HBeAg-positive CHB patients with low levels of cell frequency of Treg and Treg/Th17 ratio before entecavir treatment tended to be easier to have negative conversion of HBeAg,and changes in cell frequency of Treg during the treatment may assist the prediction of the negative conversion of HBeAg.