核苷(酸)类似物经治的慢性乙型肝炎患者低病毒血症的研究现状

鲁凤民; 封波; 郑素军; 蒋素贞; 杨瑞锋; 福军亮; 纪冬; 党双锁; 鲁晓擘; 陈红松; 陈新月; 任红; 高志良; 南月敏; 徐小元; 牛俊奇; 张文宏; 庄辉

doi:10.3969/j.issn.1001-5256.2021.06.007

核苷(酸)类似物经治的慢性乙型肝炎患者低病毒血症的研究现状

DOI: 10.3969/j.issn.1001-5256.2021.06.007

鲁凤民^{1, 2},
封波²,
郑素军³,
蒋素贞²,
杨瑞锋²,
福军亮⁴,
纪冬⁴,
党双锁⁵,
鲁晓擘⁶,
陈红松²,
陈新月³,
任红⁷,
高志良⁸,
南月敏⁹,
徐小元¹⁰,
牛俊奇¹¹,
张文宏¹²,
庄辉^1, ,

1.
北京大学基础医学院病原生物学系暨感染病中心，北京 100191
2.
北京大学人民医院, 北京大学肝病研究所，北京 100044
3.
首都医科大学附属北京佑安医院肝病中心一科，北京 100069
4.
解放军总医院第五医学中心肝纤维诊疗中心，北京 100039
5.
西安交通大学第二附属医院感染科，西安 710004
6.
新疆医科大学第一附属医院感染科·肝病中心乌鲁木齐 830054
7.
重庆医科大学病毒性肝炎研究所，重庆 400060
8.
中山大学附属第三医院感染性疾病科，广州 510630
9.
河北医科大学第三医院中西医结合肝病科，石家庄 050051
10.
北京大学第一医院感染疾病中心，北京 100034
11.
吉林大学第一医院肝胆胰内科，长春 130021
12.
复旦大学附属华山医院感染科，上海 200040

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：鲁凤民、封波、郑素军、庄辉教授负责构思主要框架及修改文章关键内容；蒋素贞、杨瑞锋、纪冬、党双锁、鲁晓擘、陈红松、陈新月、任红、高志良、南月敏、徐小元、福军亮、牛俊奇、张文宏参与修改文章。

详细信息

通信作者:
庄辉，zhuangbmu@126.com

中图分类号: R512.62
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出版历程
- 收稿日期: 2021-05-04
- 录用日期: 2021-05-12
- 出版日期: 2021-06-20

Current status of the research on low-level viremia in chronic hepatitis B patients receiving nucleos(t)ide analogues

1.
Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University, Beijing 100191, China
2.
Peking University Hepatology Institute, Peking University People's Hospital, Beijing 100044, China
3.
First Department of Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
4.
Diagnosis and Treatment Center of Hepatic Fibrosis, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
5.
Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
6.
Department of Infectious Diseases & Liver Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China
7.
Institute for Viral Hepatitis, Chongqing Medical University, Chongqing 400060, China
8.
Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
9.
Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang 050051, China
10.
Infectious Diseases Center, Peking University First Hospital, Beijing 100034, China
11.
Department of Hepatology, The First Hospital of Jilin University, Changchun 130021, China
12.
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China

摘要

摘要: 临床上广泛使用的一线抗HBV药物核苷(酸)类似物(NAs)可有效地抑制HBV DNA复制，显著减缓慢性乙型肝炎(CHB)患者的疾病进展，减少包括肝衰竭和肝癌在内的终末期肝病的发生。然而，临床上有一部分CHB患者在接受一线NAs治疗48周或更长时间后，其血清HBV DNA仍持续或间歇性地高于灵敏核酸试剂的检测下限。本文作者经讨论对低病毒血症(LLV)形成如下定义：持续性LLV，指对接受恩替卡韦、富马酸替诺福韦酯或富马酸丙酚替诺福韦治疗48周及以上的CHB患者，用灵敏的定量PCR方法至少连续检测2次，每次间隔3~6个月，HBV DNA均阳性，但＜2000 IU/ml；间歇性LLV是指用灵敏的qPCR法至少连续检测3次，每次间隔3~6个月，HBV DNA为间歇性阳性，但＜2000 IU/ml。诊断LLV应注意排除患者存在用药依从性和耐药突变的问题。LLV可能与NAs治疗下肝纤维化进展及肝硬化患者肝细胞癌风险增加有关，但目前对LLV发生后原治疗方案是否需要调整仍存在争议。综述了NAs治疗下LLV的发生率及其对临床预后的影响，并分析了LLV发生的可能机制，以期为今后NAs经治LLV患者的管理提供参考。
- 乙型肝炎, 慢性 /
- 核苷类 /
- 核苷酸类 /
- 低病毒血症
Abstract: Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, have positive for HBV DNA are positive by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but < 2000 IU/ml; intermittent LLV refers to serum HBV DNA are positive intermittently by at least three consecutive detections, with an interval of 3-6 months, but HBV DNA < 2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis, or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.
- Hepatitis B, Chronic /
- Nucleosides /
- Nucleotides /
- Low-Level Viremia

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