血清RANTES早期下降可预测联合聚乙二醇干扰素α治疗核苷(酸)类似物经治慢性乙型肝炎患者的HBsAg清除

Early reduction of serum RANTES can predict HBsAg clearance in patients with chronic hepatitis B treated with nucleos(t)ide analogues combined with peginterferon alpha

目的观察核苷(酸)类似物(NAs)经治慢性乙型肝炎患者在联合聚乙二醇干扰素α治疗过程中血清RANTES的动态变化,并分析RANTES对HBsAg清除的预测作用。方法入组98例NAs治疗≥1年达到HBsAg定量<3000 IU/ml、HBV DNA<20 IU/ml的慢性乙型肝炎患者,其中26例继续NAs单药治疗,72例NAs联合聚乙二醇干扰素α治疗,观察治疗过程中RANTES变化情况,并通过受试者操作特征曲线分析RANTES早期变化预测48周HBsAg清除的作用。结果48周时,联合组有15例患者(20.83%)达到HBsAg清除,NAs组无患者达到HBsAg清除;NAs组与联合组患者血清RANTES整体水平均较基线下降;联合组中48周HBsAg清除的患者较未清除的患者血清RANTES水平下降更为显著。对联合组进一步分析发现,联合聚乙二醇干扰素α治疗后12周、24周血清RANTES水平下降的患者HBsAg清除率明显高于RANTES上升的患者(29.17%比4.17%,P=0.014;28.00%比4.55%,P=0.052),HBsAg定量下降幅度也更大[(1.49±1.26)log_(10)IU/ml比(0.73±0.81)log_(10)IU/ml,P=0.017;(1.54±1.27)log_(10)IU/ml比(0.57±0.56)log_(10)IU/ml,P=0.004]。受试者操作特征曲线分析显示,基线HBsAg定量、HBsAg和血清RANTES早期下降均可预测联合治疗48周HBsAg清除。基线HBsAg定量联合12周或24周RANTES下降相较于基线HBsAg定量联合12周或24周HBsAg定量下降幅度具有更优的预测48周HBsAg清除的作用,前者受试者操作特征曲线下面积分别为0.925、0.939,后者受试者操作特征曲线下面积分别为0.909、0.929。结论NAs经治慢性乙型肝炎患者联合聚乙二醇干扰素α治疗12或24周血清RANTES下降,可能是预测患者治疗48周HBsAg清除的关键免疫学指标之一。

Objective To observe the dynamic changes of serum RANTES during the treatment with nucleos(t)ide analogues combined with pegylated interferon alpha(peginterferon-α),and further analyze the predictive effect of RANTES on HBsAg clearance in patients with chronic hepatitis B.Methods 98 cases of chronic hepatitis B with quantitative HBsAg<3000 IU/ml and HBV DNA<20 IU/ml after≥1 year NAs treatment were enrolled.Among them,26 cases continued to receive NAs monotherapy,72 cases received NAs combined with pegylated interferon alpha therapy.The changes in RANTES during treatment were observed.The receiver operating characteristic curve was used to analyze the early changes of RANTES to predict the HBsAg clearance during 48 weeks.Results During 48 weeks,15 cases(20.83%)had achieved HBsAg clearance in combination group,while no patient had achieved HBsAg clearance in NAs group.The overall serum RANTES level had decreased from baseline in NAs and combination group.At week 48,in the combination group,the serum RANTES level was decreased more significantly in patients with HBsAg clearance than patients without.Further analysis showed that,in combination group,HBsAg clearance rate of patients with serum RANTES decreased at week 12 and 24 was higher than patients with elevated(29.17%vs.4.17%,P=0.014;28.00%vs.4.55%,P=0.052),and quantitative HBsAg reduction was larger significantly[(1.49±1.26)log_(10)IU/ml vs.(0.73±0.81)log_(10)IU/ml,P=0.017;(1.54±1.27)log_(10)IU/ml vs.(0.57±0.56)log_(10)IU/ml,P=0.004].Receiver operating characteristic curve analysis showed that the baseline quantitative HBsAg and the reduction in quantitative HBsAg and serum RANTES during the early period were predictors of HBsAg clearance after 48-week combination therapy.Furthermore,the combination of baseline quantitative HBsAg and 12-or 24-week reduction of serum RANTES were better predictors of HBsAg clearance than that of baseline quantitative HBsAg combined with HBsAg decrease at week 12 or 24.The area under the receiver operating characteristic curve of the former was 0.925 and 0.939,while that of the latter was 0.909 and 0.929,respectively.Conclusion Early reduction of serum RANTES at week 12 and 24 can predict HBsAg loss in CHB patients receiving addition of peginterferon-αto ongoing NAs Therapy,so serum RANTES could be one of the key immunological markers for predicting HBsAg clearance.