血清乙型肝炎病毒RNA水平可预测接受核苷（酸）类似物治疗的高病毒载量慢性乙型肝炎患者的HBeAg血清学转换和病毒学应答。
Serum Hepatitis B Virus RNA Levels Predict HBeAg Seroconversion and Virological Response in Chronic Hepatitis B Patients with High Viral Load Treated with Nucleos(t)ide Analog.
作者信息
Ji Xin, Xia Muye, Zhou Bin, Liu Shi, Liao GuiChan, Cai Shaohang, Zhang Xiaoyong, Peng Jie
机构信息
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
出版信息
Infect Drug Resist. 2020 Jun 22;13:1881-1888. doi: 10.2147/IDR.S252994. eCollection 2020.
BACKGROUND AND AIM
Hepatitis B virus (HBV) RNA has attracted increasing attention as a novel serum marker for intrahepatic HBV replication. However, the predictive value of the serum level of HBV RNA for hepatitis B e-antigen (HBeAg) seroconversion and viral response among patients with a high viral load (HVL) is unclear. We evaluated the role of the serum level of HBV RNA as a predictor of treatment response in chronic HBV (CHB) patients with an HVL.
PATIENTS AND METHODS
The study cohort was 66 HBeAg-positive CHB patients with an HVL (serum HBV DNA >1.9×10 IU/mL) at baseline from our previous prospective cohort study treated with lamivudine (LAM) and adefovir dipivoxil(ADV) (N=31) or entecavir alone (N=35) for ≤96 weeks. The serum HBV RNA level was quantified by TaqMan probe-based reverse transcription real-time quantitative polymerase chain reaction at four time points.
RESULTS
The baseline serum HBV RNA level (in log copies/mL) in patients treated with LAM+ADV and ETV monotherapy was 8.97±1.22 and 9.15±0.92, respectively. After nucleos(t)ide analog (NA) therapy, the serum HBV RNA level decreased steadily in all patients (week 0 vs week 12, p<0.001; week 12 vs week 24, p=0.010; week 24 vs week 48, p<0.001). Fifty-three (80.3%) patients achieved a virologic response (VR), and 12 (18.2%) achieved HBeAg seroconversion after 96 weeks. Multivariate analyses revealed that the serum HBV RNA level at week 12 could predict HBeAg seroconversion (OR 3.560, 95% CI: 1.39-9.110, p=0.008) and VR (1.908, 1.115-3.265, 0.018) at 96 weeks. Analyses of receiver operating characteristic curves indicated that the serum HBV RNA level 12 weeks after NA treatment had predictive value for HBeAg seroconversion (AUC=0.847, p<0.001) and VR (AUC=0.736, p=0.011).
CONCLUSION
The serum level of HBV RNA at 12 weeks could predict HBeAg seroconversion and a VR during NA treatment in CHB patients with an HVL.
背景与目的
乙肝病毒（HBV）RNA作为肝内HBV复制的一种新型血清标志物，已引起越来越多的关注。然而，高病毒载量（HVL）患者血清中HBV RNA水平对乙肝e抗原（HBeAg）血清学转换和病毒应答的预测价值尚不清楚。我们评估了血清HBV RNA水平在HVL慢性乙肝（CHB）患者治疗应答预测中的作用。
患者与方法
研究队列包括66例基线时HBeAg阳性的HVL CHB患者（血清HBV DNA>1.9×10 IU/mL），这些患者来自我们之前的前瞻性队列研究，接受拉米夫定（LAM）和阿德福韦酯（ADV）联合治疗（N = 31）或单用恩替卡韦治疗（N = 35）≤96周。在四个时间点通过基于TaqMan探针的逆转录实时定量聚合酶链反应对血清HBV RNA水平进行定量。
结果
接受LAM + ADV和ETV单药治疗的患者基线血清HBV RNA水平（以log拷贝/mL计）分别为8.97±1.22和9.15±0.92。核苷（酸）类似物（NA）治疗后，所有患者血清HBV RNA水平均稳步下降（第0周与第12周，p<0.001；第12周与第24周，p = 0.010；第24周与第48周，p<0.001）。53例（80.3%）患者实现了病毒学应答（VR），12例（18.2%）患者在96周后实现了HBeAg血清学转换。多因素分析显示，第12周时血清HBV RNA水平可预测96周时的HBeAg血清学转换（OR 3.560，95%CI：1.39 - 9.110，p = 0.008）和VR（1.908，1.115 - 3.265，0.018）。受试者工作特征曲线分析表明，NA治疗12周后的血清HBV RNA水平对HBeAg血清学转换（AUC = 0.847，p<0.001）和VR（AUC = 0.736，p = 0.011）具有预测价值。
结论
12周时血清HBV RNA水平可预测HVL CHB患者在NA治疗期间的HBeAg血清学转换和VR。
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