慢性乙型肝炎患者外周血Treg/Th17比值平衡及其对替比夫定治疗效果的影响

目的 探讨慢性乙型肝炎(CHB)患者外周血调节性T淋巴细胞(Treg)/辅助性T细胞17(Th17)平衡及其对替比夫定治疗应答的预测能力。方法 2019年2月～2020年3月我院诊治的123例CHB患者和112例乙型肝炎病毒携带者,另选同期健康人95例,给予CHB患者替比夫定治疗48 w,使用流式细胞仪检测外周血Treg细胞和Th17细胞百分比,计算Treg/Th17比值。采用Logistic多因素回归模型分析影响替比夫定治疗应答的因素,应用受试者工作特征曲线(ROC)下面积(AUC)分析Treg/Th17比值预测替比夫定治疗应答的价值。结果 CHB患者外周血Treg细胞和Th17细胞百分比及Treg/Th17比值分别为(4.8±1.1)%、(6.1±1.7)%和(0.8±0.1),显著高于HBV携带者分别为(1.1±0.3)%、(2.5±0.8)%和(0.4±0.0),P＜0.05]或健康人分别为(0.9±0.2)%、(2.1±0.6)%和(0.4±0.0),P＜0.05);在治疗12 w、24 w和48 w, CHB患者血清ALT复常率分别为65.9%、77.2%和93.5%,HBV DNA阴转率分别为61.8%、72.4%和82.9%;在治疗48 w末,21例(17.1%)CHB患者不应答;不应答组复治、服药依从性差、血清ALT水平低、基线HBV DNA载量高、Treg细胞百分比高和Treg/Th17比值高的比率显著高于应答组(P均<0.05);Logistic回归分析显示,复治、基线HBV DNA载量、ALT水平和Treg/Th17比值均为影响替比夫定治疗不应答的独立预测因素(OR=3.695、OR=3.232、OR=3.866、OR=4.039,P均<0.05);ROC分析显示,Treg/Th17比值预测替比夫定治疗不应答的最佳截断点为0.83,AUC为0.923(95%CI:0.860～0.963),其灵敏度为81.0%,特异度为87.3%,准确度为91.1%。结论 CHB患者外周血Treg细胞百分比和Treg/Th17细胞比值异常升高,可能影响替比夫定抗病毒治疗效果,其机制值得进一步研究。

Balance of peripheral blood Treg cells/Th17 cells in patients with chronic hepatitis B and its impact on response to telbivudine treatment

Objective The aim of this study was to investigate the balance of peripheral blood regulatory T lymphocytes(Treg)/helper T cell 17(Th17)in patients with chronic hepatitis B(CHB)and its impact on response to telbivudine treatment.Methods 123 patients with CHB,112 hepatitis B viral carriers and 95 healthy persons were recruited in this study in our hospital between February 2019 and March 2020,and all CHB patients received telbivudine treatment for 48 weeks.Peripheral blood Treg and Th17 cell percentages were detected by FCM.The multivariate Logistic regression was applied to analyze the impacting factors of non-response to nucleotide analogue treatment in patients with CHB.The area under the receiver operating characteristic curve(AUROC)was applied to analyze the efficacy of Treg/Th17 ratio in predicting the response to antiviral treatment.Results The percentages of Treg cells and Th17 cells as well as Treg/Th17 ratio in patients with CHB were(4.8±1.1)%,(6.1±1.7)%and(0.8±0.1),significantly higher than(1.1±0.3)%,(2.5±0.8)%and(0.4±0.0),P<0.05]in HBV carriers,or(0.9±0.2)%,(2.1±0.6)%and(0.4±0.0),P<0.05]in healthy persons;at the end of week 12,week 24 and week 48,the normalization rates of serum ALT levels were 65.9%,77.2%and 93.5%,serum HBV DNA loss were 61.8%,72.3%and 82.9%;at the end of week 48,21 patients(17.1%)failed to response to antiviral treatment;the percentages of re-treated patients,poor medication compliance,low baseline serum ALT and HBV DNA loads,Treg cells and Treg/Th17 ratios in non-responders were significantly different as compared to those in response group(all P<0.05);the Logistic regression analysis showed that re-treatment,baseline HBV DNA load and ALT levels,and Treg/Th17 ratio were the independent factors for non-response to nucleotide analog treatment in patients with CHC(OR=3.695,OR=3.232,OR=3.866,OR=4.039,all P<0.05);the ROC analysis showed that the optimal cut-off value of blood Treg/Th17 ratio for predicting non-response to nucleotide analogues treatment in patients with CHB was 0.83,with the AUC of 0.923(95%CI:0.860-0.963),ant its sensitivity of 81.0%,the specificity of 87.3%,and the accuracy of 91.1%.Conclusion The percentages of peripheral blood Treg cells increase in patients with CHB,which might impact on the response to antiviral therapy and need further investigation.