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, China.
Aliment Pharmacol Ther. 2020 Aug;52(4):692-700. doi: 10.1111/apt.15890. Epub 2020 Jul 1.
Serum hepatitis B virus (HBV) RNA is a novel biomarker for evaluating treatment response. Detailed information regarding serum HBV RNA kinetics during treatment with nucleos(t)ide analogues (NAs) is limited.
To ascertain serum HBV RNA kinetics during long-term NA treatment and identify associated factors.
We enrolled 76 HBeAg-positive chronic hepatitis B patients receiving NA from randomised controlled trials. Laboratory assays were undertaken every 3 months. Factors associated with serum HBV RNA kinetics were identified by generalised estimating equations.
Baseline serum HBV RNA was 8.5 ± 1.0 log copies/mL. Decline in serum HBV RNA during NA therapy was biphasic: the first phase (HBV DNA detectable) had a fast decrease (median slope, -0.207 log copies/mL/month) and was followed by a second phase (HBV DNA undetectable) with slow decrease (median slope, -0.071 log copies/mL/month). In the first phase, factors independently associated with lower initial serum HBV RNA were male sex (OR, 0.685, P = 0.044), low baseline HBsAg (OR, 0.525, P = 0.001) and rapid virological response (RVR) (OR, 0.624, P = 0.031). In the second phase, only RVR was independently associated with serum HBV RNA kinetics, including its lower initial level (OR, 0.694, P = 0.043) and greater decline (OR, 0.966, P = 0.002). Based on viral dynamics, time needed to achieve undetectable serum HBV RNA from baseline was 43.56 (IQR: 29.49-66.40) months.
RVR was a significant determinant for biphasic decline in serum HBV RNA during NA treatment, which significantly influenced the treatment duration required to achieve undetectable serum HBV RNA.
血清乙型肝炎病毒 (HBV) RNA 是评估治疗应答的新型生物标志物。关于核苷（酸）类似物 (NA) 治疗期间血清 HBV RNA 动力学的详细信息有限。
确定长期 NA 治疗期间血清 HBV RNA 动力学，并确定相关因素。
我们纳入了来自随机对照试验的 76 例 HBeAg 阳性慢性乙型肝炎患者。每 3 个月进行一次实验室检测。通过广义估计方程确定与血清 HBV RNA 动力学相关的因素。
基线时血清 HBV RNA 为 8.5±1.0 log 拷贝/mL。NA 治疗期间血清 HBV RNA 下降呈双相：第一相（HBV DNA 可检测）下降迅速（中位数斜率，-0.207 log 拷贝/mL/月），随后第二相（HBV DNA 不可检测）下降缓慢（中位数斜率，-0.071 log 拷贝/mL/月）。在第一相，与初始血清 HBV RNA 较低相关的独立因素为男性（OR，0.685，P=0.044）、低基线 HBsAg（OR，0.525，P=0.001）和快速病毒学应答（RVR）（OR，0.624，P=0.031）。在第二相，只有 RVR 与血清 HBV RNA 动力学独立相关，包括其初始水平较低（OR，0.694，P=0.043）和下降幅度较大（OR，0.966，P=0.002）。基于病毒动力学，从基线达到不可检测血清 HBV RNA 所需的时间为 43.56（IQR：29.49-66.40）个月。
RVR 是 NA 治疗期间血清 HBV RNA 双相下降的重要决定因素，显著影响达到不可检测血清 HBV RNA 所需的治疗时间。
