基于核酸聚合酶的治疗过程中 HBsAg 快速单相下降预示着功能性治愈。
Rapid monophasic HBsAg decline during nucleic-acid polymer-based therapy predicts functional cure.
机构信息
Program for Experimental & Theoretical Modeling, Department of Medicine, Division of Hepatology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA.
Network Science Institute, Northeastern University, Boston, Massachusetts, USA.
出版信息
Hepatol Commun. 2023 Jul 17;7(8). doi: 10.1097/HC9.0000000000000205. eCollection 2023 Aug 1.
BACKGROUND AND AIMS
Analyzing the interplay among serum HBV DNA, HBsAg, anti-HBs, and alanine aminotransferase (ALT) during nucleic-acid polymer (NAP)-based therapy for chronic hepatitis B provides a unique opportunity to identify kinetic patterns associated with functional cure.
METHODS
All participants with HBeAg-negative chronic HBV infection in the REP 401 study (NCT02565719) first received 24 weeks of tenofovir-disoproxil-fumarate (TDF) monotherapy. The early triple therapy group (n = 20) next received 48 weeks of TDF+pegylated interferon-α2a (pegIFN)+NAPs. In contrast, the delayed triple therapy group (n = 20) next received 24 weeks of TDF+pegIFN before 48 weeks of triple therapy. Three participants discontinued treatment and were excluded. Functional cure (HBsAg and HBV DNA not detectable with normal ALT) was assessed at 48 weeks post-treatment. Different kinetic phases were defined by at least a 2-fold change in slope. A single-phase decline was categorized as monophasic, and 2-phase declines were categorized as biphasic.
RESULTS
Fourteen (35%) participants achieved a functional cure. HBV DNA remained below or near undetectable for all participants by the end of TDF monotherapy and during subsequent combination therapies. Three HBsAg kinetic patterns were found in both the early and delayed groups, nonresponders (n = 4 and n = 4), monophasic (n = 11 and n = 11), and biphasic (n = 4 and n = 3), respectively. All participants who achieved a functional cure had a monophasic HBsAg kinetic pattern during triple therapy. Among participants with a monophasic HBsAg decline, those who had a functional cure had a shorter median time to HBsAg loss of 21 (interquartile range=11) weeks compared with those who did not achieve functional cure [median: 27 (7) weeks] (p = 0.012).
CONCLUSIONS
Functional cure was associated with a rapid monophasic HBsAg decline during NAP-based therapy. A nonmonophasic HBsAg kinetic pattern had a 100% negative predictive value (NPV) for a functional cure.
背景与目的
分析基于核酸聚合物（NAP）治疗慢性乙型肝炎期间血清 HBV DNA、HBsAg、抗-HBs 和丙氨酸氨基转移酶（ALT）之间的相互作用，为识别与功能性治愈相关的动力学模式提供了独特的机会。
方法
REP 401 研究（NCT02565719）中所有 HBeAg 阴性慢性 HBV 感染的参与者首先接受 24 周替诺福韦酯（TDF）单药治疗。早期三联治疗组（n = 20）随后接受 48 周 TDF+聚乙二醇干扰素-α2a（pegIFN）+NAPs 治疗。相比之下，延迟三联治疗组（n = 20）随后在接受 24 周 TDF+pegIFN 治疗后接受 48 周三联治疗。3 名参与者停止治疗并被排除在外。治疗后 48 周评估功能性治愈（HBsAg 和 HBV DNA 不可检测，ALT 正常）。通过斜率至少变化 2 倍来定义不同的动力学阶段。单相下降被归类为单相，两相下降被归类为双相。
结果
14 名（35%）参与者实现了功能性治愈。所有参与者在 TDF 单药治疗结束时以及随后的联合治疗期间，HBV DNA 均保持在检测下限或接近检测下限。在早期和延迟组中均发现了 3 种 HBsAg 动力学模式，无应答者（n = 4 和 n = 4）、单相（n = 11 和 n = 11）和双相（n = 4 和 n = 3）。在三联治疗期间，所有实现功能性治愈的参与者均表现出单相 HBsAg 动力学模式。在具有单相 HBsAg 下降的参与者中，与未实现功能性治愈的参与者相比，那些实现功能性治愈的参与者 HBsAg 丢失的中位时间更短，为 21 周（四分位间距=11 周），而未实现功能性治愈的参与者为 27 周（中位数：7 周）（p = 0.012）。
结论
NAP 治疗期间功能性治愈与快速单相 HBsAg 下降相关。非单相 HBsAg 动力学模式对功能性治愈具有 100%的阴性预测值（NPV）。
Zotero 插件