慢性乙型肝炎患者血清乙型肝炎病毒RNA对核苷(酸)类似物治疗后HBeAg清除和血清转化的预测价值  

Utility of serum HBV RNA for predicting HBeAg clearance and seroconversion after treatment with nucleoside analogs in chronic hepatitis B patients

作　　者：曲紫瑶 孙建光 孔庆辉[2] 王子宜 QU Ziyao;SUN Jianguang;KONG Qinghui;WANG Ziyi(The First Clinical Medical School of Shandong University of Traditional Chinese Medicine,Jinan 250014,China)

机构地区：[1]山东中医药大学第一临床医学院,济南250014 [2]山东中医药大学附属威海医院肝病科

出　　处：《中国感染与化疗杂志》2024年第5期521-529,共9页Chinese Journal of Infection and Chemotherapy

基　　金：山东省科技发展计划项目(2019-0962)。

摘　　要：目的探讨慢性乙型肝炎(CHB)患者血清乙型肝炎病毒(HBV)RNA对核苷(酸)类似物(NA)治疗后乙型肝炎病毒e抗原(HBeAg)清除和血清转化的预测价值。方法收集2017年2月12日至2019年2月21日在山东中医药大学附属威海医院首次接受NA单药治疗的178例CHB患者的血清样本。采用实时荧光定量PCR法定量检测基线和NA治疗后血清HBV RNA水平。结果HBeAg清除组和血清转化组患者基线、治疗6个月时和12个月时的血清HBV RNA水平分别显著低于未清除组和未转化组(P<0.001)。随访期间,基线HBV RNA水平较低的患者累积HBeAg清除率(Log Rankχ^(2)=11.282,P=0.001)或血清转化率(Log Rankχ^(2)=10.739,P=0.001)高于较高水平的患者。经Cox回归模型分析,基线、治疗6个月和12个月时的血清HBV RNA是CHB患者HBeAg清除和血清转化的独立影响因素(P<0.05)。基线血清HBV RNA水平预测HBeAg清除和血清转化的ROC曲线下面积(AUC)分别为0.808(95%CI:0.743~0.872)和0.824(95%CI:0.763~0.885);治疗6个月时的AUC分别为0.830(95%CI:0.765~0.894)和0.732(95%CI:0.657~0.808);治疗12个月时的AUC分别为0.737(95%CI:0.641~0.833)和0.757(95%CI:0.671~0.842)。基线血清HBV RNA联合6个月时HBV RNA下降程度预测AUC分别为0.856(95%CI:0.795~0.917)和0.864(95%CI:0.802~0.926);联合12个月时HBV RNA下降程度预测AUC分别为0.881(95%CI:0.826~0.936)和0.848(95%CI:0.784~0.911)。结论CHB患者血清HBV RNA水平对NA治疗后HBeAg清除和血清转化具有较高的预测价值,提示HBV RNA水平可以帮助识别无反应者并促使考虑联合治疗。Objective To investigate the value of serum hepatitis B virus(HBV)RNA for predicting hepatitis B virus e antigen(HBeAg)clearance and seroconversion after nucleoside(acid)analogs(NAs)treatment in patients with chronic hepatitis B(CHB).Methods Serum samples were collected from 178 CHB patients who received NAs monotherapy in Weihai Hospital affiliated to Shandong University of Traditional Chinese Medicine from February 12,2017 to February 21,2019.Serum HBV RNA levels were analyzed by real-time fluorescence-based quantitative PCR at baseline and after NAs treatment.Results The patients with HBeAg clearance and seroconversion showed significantly lower serum HBV RNA levels at baseline,6 months and 12 months of treatment compared with those without HBeAg clearance and seroconversion(P<0.001).During follow-up,the patients with lower baseline HBV RNA levels had higher rate of cumulative HBeAg clearance(Log Rankχ^(2)=11.282,P=0.001)or seroconversion(Log Rankχ^(2)=10.739,P=0.001)than the patients with higher baseline HBV RNA levels.Cox regression model analysis indicated that serum HBV RNA levels at baseline,6 months and 12 months of treatment were an independent predictor for HBeAg clearance and seroconversion in CHB patients (P < 0.05). The area under the ROC curve (AUC) of baseline serumHBV RNA level was 0.808 (95% CI: 0.743-0.872) for predicting HBeAg clearance and 0.824 (95% CI: 0.763-0.885) for predictingseroconversion. The AUC of HBV RNA level at 6 months of treatment was 0.830 (95% CI: 0.765-0.894) for predicting HBeAgclearance and 0.732 (95% CI: 0.657-0.808) for predicting seroconversion. The AUC of HBV RNA level at 12 months of treatmentwas 0.737 (95% CI: 0.641-0.833) for predicting HBeAg clearance and 0.757 (95% CI: 0.671-0.842) for predicting seroconversion.The AUC of baseline HBV RNA level combined with HBV RNA decline at 6 months of treatment was 0.856 (95% CI: 0.795-0.917)for predicting HBeAg clearance and 0.864 (95% CI: 0.802-0.926) for predicting seroconversion. The AUC of baseline HBV RNAlevel combined

关 键 词：慢性乙型肝炎 HBV RNA 核苷(酸)类似物 HBeAg清除 HBeAg血清转化 

分 类 号：R512.62[医药卫生—内科学]