Factors associated with the biphasic kinetics of serum HBV RNA in patients with HBeAg-positive chronic hepatitis B treated with nucles(t)ide analogues
Factors associated with the biphasic kinetics of serum HBV RNA in patients with HBeAg-positive chronic hepatitis B treated with nucles(t)ide analogues
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核（酸）类似物治疗 HBeAg 阳性慢性乙型肝炎患者血清 HBV RNA 双相动力学的相关因素
DOI：
10.1111/apt.15890
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发表时间：
2020-07-01
影响因子：
7.6
通讯作者：
Sun, Jian
中科院分区：
文献类型：
--
作者：
Liu, Shi;Liu, Zhihong;Sun, Jian
背景：血清B型肝炎病毒（HBV）RNA是评价治疗反应的一种新的生物标志物。关于核苷（酸）类似物（NAs）治疗期间血清HBV RNA动力学的详细信息有限。目的确定长期NAs治疗期间血清HBV RNA的动力学，并确定相关因素。方法我们从随机对照试验中纳入了76例HBeAg阳性的慢性B型肝炎患者接受NAs治疗。每3个月进行一次实验室测定。通过广义估计方程确定与血清HBV RNA动力学相关的因素。结果基线血清HBV RNA为8.5 +/- 1.0 log（10）copies/mL。NAs治疗期间血清HBV RNA下降呈双相性：第一阶段（HBV DNA可检测）快速下降（中位斜率，-0.207 log（10）拷贝/mL/月），随后是第二阶段（HBV DNA不可检测）缓慢下降（中位斜率，-0.071 log（10）拷贝/mL/月）。在第一阶段，与低初始血清HBV RNA独立相关的因素为男性（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）。在第二阶段，只有RVR与血清HBV RNA动力学独立相关，包括较低的初始水平（OR，0.694，P = 0.043）和较大的下降幅度（OR，0.966，P = 0.002）。根据病毒动力学，从基线至血清HBV RNA不可检出所需的时间为43.56（IQR：29.49-66.40）个月。结论RVR是NAs治疗期间血清HBV RNA双相下降的重要决定因素，其显著影响达到血清HBV RNA不可检测所需的治疗时间。
Background Serum hepatitis B virus (HBV) RNA is a novel biomarker for evaluating treatment response. Detailed information regarding serum HBV RNA kinetics during treatment with nucles(t)ide analogues (NAs) is limited. Aims To ascertain serum HBV RNA kinetics during long-term NAs treatment and identify associated factors. Methods We enrolled 76 HBeAg-positive chronic hepatitis B patients receiving NAs from randomised controlled trials. Laboratory assays were undertaken every 3 months. Factors associated with serum HBV RNA kinetics were identified by generalised estimating equations. Results Baseline serum HBV RNA was 8.5 +/- 1.0 log(10) copies/mL. Decline in serum HBV RNA during NAs therapy was biphasic: the first phase (HBV DNA detectable) had a fast decrease (median slope, -0.207 log(10) copies/mL/month) and was followed by a second phase (HBV DNA undetectable) with slow decrease (median slope, -0.071 log(10) 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. Conclusion RVR was a significant determinant for biphasic decline in serum HBV RNA during NAs treatment, which significantly influenced the treatment duration required to achieve undetectable serum HBV RNA.