中国感染与化疗杂志2024,Vol.24Issue(5) :521-529.DOI:10.16718/j.1009-7708.2024.05.004

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

曲紫瑶 孙建光 孔庆辉 王子宜
中国感染与化疗杂志2024,Vol.24Issue(5) :521-529.DOI:10.16718/j.1009-7708.2024.05.004

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

曲紫瑶 1孙建光 1孔庆辉 2王子宜2
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作者信息

  • 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
  • 折叠

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 Rank x2=11.282,P=0.001)或血清转化率(Log Rank x2=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.

Abstract

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 Rank x2=11.282,P=0.001)or seroconversion(Log Rank x2=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 serum HBV 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 predicting seroconversion.The AUC of HBV RNA level at 6 months of treatment was 0.830(95%CI:0.765-0.894)for predicting HBeAg clearance and 0.732(95%CI:0.657-0.808)for predicting seroconversion.The AUC of HBV RNA level at 12 months of treatment was 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 RNA level combined with HBV RNA decline at 12 months of treatment was 0.881(95%CI:0.826-0.936)for predicting HBeAg clearance and 0.848(95%CI:0.784-0.911)for predicting seroconversion.Conclusions Serum HBV RNA levels have high predictive value for HBeAg clearance and seroconversion after NAs therapy in CHB patients,suggesting that HBV RNA levels are helpful for identifying non-responders and informing combination therapy.

关键词

慢性乙型肝炎/HBVRNA/核苷(酸)类似物/HBeAg清除/HBeAg血清转化

Key words

chronic hepatitis B/HBV RNA/nucleos(t)ide analogues/HBeAg clearance/HBeAg seroconversion

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基金项目

山东省科技发展计划项目(2019-0962)

出版年

2024
中国感染与化疗杂志
复旦大学附属华山医院

中国感染与化疗杂志

CSTPCDCSCD北大核心
影响因子:3.776
ISSN:1009-7708
参考文献量17
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