核苷（酸）类似物时代慢性乙型肝炎抗病毒治疗中血清HBV RNA

StephenW

Front Med. 2017 Nov 23. doi: 10.1007/s11684-017-0590-z. [Epub ahead of print]
Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide analogs.Lu F1, Wang J2, Chen X2, Xu D3, Xia N4.
Author information
1State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. [email protected].2State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.3Institute of Infectious Diseases, Beijing 302 Hospital, Beijing, 100039, China.4State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, 361102, China.

AbstractAlthough the efficacy of nucleos(t)ide analogue (NA) has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and disease relapse. In this review, the RNA virion-like particles of hepatitis B virus (HBV) are integrated into the life cycle of HBV replication, and the potential significance of serum HBV RNA is systematically described. The production of HBV RNA virion-like particles should not be blocked by NA; in this regard, serum HBV RNA is found to be a suitable surrogate marker for the activity of intrahepatic covalently closed circular DNA (cccDNA), particularly among patients receiving NA therapy. Therefore, the concept of virological response is redefined as persistent loss of serum HBV DNA and HBV RNA. In contrast to hepatitis B surface antigen (HBsAg) that can originate from either the cccDNA or the integrated HBV DNA fragment, serum HBV RNA, with pregenomic RNA origination, can only be transcribed from cccDNA. Therefore, the loss of serum HBV RNA would likely be a promising predicator for safe drug discontinuation. The clinical status of consistent loss of serum HBV RNA accompanied with low serum HBsAg levels might be implicated as a "para-functional cure," a status nearly close to the functional cure of chronic hepatitis B, to distinguish the "functional cure" characterized as serum HBsAg loss with or without anti-HBs seroconversion.


KEYWORDS: chronic hepatitis B; nucleos(t)ide analogs; para-functional cure; serum HBV RNA; virological response

PMID:29170915DOI:10.1007/s11684-017-0590-z

StephenW

Front Med。 2017年11月23日。doi：10.1007 / s11684-017-0590-z。 [电子版提前打印]
核苷（酸）类似物时代慢性乙型肝炎抗病毒治疗中血清HBV RNA的潜在应用。
鲁F1，王J2，陈X2，许D3，夏N4。
作者信息

1
    北京大学医学部基础医学院微生物与传染病中心天然药物及仿生药物国家重点实验室，北京100191 [email protected]。
2
    北京大学医学部基础医学院微生物与传染病中心天然药物及仿生药物国家重点实验室，北京100191
3
    北京302医院感染病研究所，北京100039
4
    厦门大学公共卫生学院分子免疫学与分子诊断国家重点实验室，厦门361102

抽象

尽管核苷（酸）类似物（NA）的功效已被证实用于治疗慢性乙型肝炎，但已推荐长期治疗，因为治疗中病毒DNA脱离反应和疾病复发的频率较高。本文综述了乙型肝炎病毒（HBV）病毒颗粒与乙型肝炎病毒复制的生命周期的整合，并对血清HBV RNA的潜在意义进行了系统的阐述。 NA RNA病毒粒子样颗粒的产生不应被NA阻断;在这方面，发现血清HBV RNA是肝内共价闭合环状DNA（cccDNA）活性的适宜替代标志物，特别是在接受NA治疗的患者中。因此，病毒学应答的概念被重新定义为血清HBV DNA和HBV RNA的持续丢失。与可能来源于cccDNA或整合的HBV DNA片段的乙型肝炎表面抗原（HBsAg）相反，具有前基因组RNA起始的血清HBV RNA只能从cccDNA转录。因此，血清HBV RNA的丢失可能是安全停用药物的有希望的预测因子。血清HBV RNA持续缺失伴低血清HBsAg水平的临床状态可能与“功能性治愈”有关，这种状态与慢性乙型肝炎的功能性治愈近乎相似，可以区分“功能性治愈”血清HBsAg消失，伴或不伴抗HBs血清转换。
关键词：

慢性乙型肝炎;核苷（酸）类似物;功能性治愈;血清HBV RNA;病毒学应答

结论：
    29170915
DOI：
    10.1007 / s11684-017-0590-Z

windu

下轮新药数据发布密集期应该是明年欧肝会期间了

Hepbest

回复 StephenW 的帖子

1. 血清HBV RNA可以作为功能性治愈的指标，但是目前血清HBV RNA的敏感性不高，HBeAg阴性大部分很难检测到，需要提高HBV RNA的检测的敏感性
2. 血清HBV RNA的消失真正反映的是cccDNA的消失，只是在一定区间内，HBV RNA比较低的情况下，还有待于验证；
3. HBsAg的下降会导致血清HBV RNA的下降，反之则不然，因为存在着空壳HBsAg影响检测的结果；