血清HBV RNA定量在指导慢性乙型肝炎抗病毒治疗过程中的作用

卞丹丹; 郑素军

doi:10.3969/j.issn.1001-5256.2020.08.035

血清HBV RNA定量在指导慢性乙型肝炎抗病毒治疗过程中的作用

DOI: 10.3969/j.issn.1001-5256.2020.08.035

1. 首都医科大学电力教学医院感染性疾病科
2. 首都医科大学附属北京佑安医院疑难肝病与人工肝中心
3. 肝衰竭与人工肝治疗研究北京市重点实验室

基金项目:

国家“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项“十三五”计划(2017ZX10202203-006,2017ZX10302201-004)；

详细信息

中图分类号: R512.62
计量
- 文章访问数: 913
- HTML全文浏览量: 46
- PDF下载量: 245
- 被引次数: 0
出版历程
- 出版日期: 2020-08-20

Role of serum hepatitis B virus RNA quantification in guiding antiviral therapy for chronic hepatitis B

Department of Infectious Diseases, Electric Power Teaching Hospital, Capital Medical University

Research funding:

摘要

摘要:
慢性HBV感染及其所致终末期肝病严重威胁着我国公民健康。HBV cccDNA的存在是慢性乙型肝炎难以治愈和停药后容易复发的主要原因。HBV RNA作为一种新的血清标志物,由cccDNA转录产生,理论上其能够反映肝细胞内cccDNA的水平及转录活性。主要介绍了血清HBV RNA的形成过程,并分析了其在评估肝组织内cccDNA活性或状态,以及在预测抗病毒治疗过程中和停药后患者应答情况等方面的意义。指出血清HBV RNA检测的临床意义需要大规模的临床研究予以验证和完善,进一步优化抗病毒治疗方案,指导患者的精准化治疗。
- 乙型肝炎,慢性 /
- HBV RNA /
- 治疗学
Abstract:
Chronic hepatitis B virus(HBV) infection and end-stage liver disease caused by such infection pose a serious threat to the health of Chinese citizens.The presence of HBV ccc DNA is the main reason for the difficulties in the treatment of chronic hepatitis B and recurrence after drug withdrawal.HBV RNA,as a new serum marker,is produced by ccc DNA transcription,and theoretically,it can reflect the level and transcriptional activity of ccc DNA in hepatocytes.This article mainly introduces the formation of serum HBV RNA and analyzes its significance in evaluating the activity or status of ccc DNA in liver tissue and predicting patients' response during antiviral therapy and after drug withdrawal.Moreover,it is pointed out that further large-scale clinical studies are needed to verify and improve the clinical significance of serum HBV RNA measurement,so as to further optimize the regimens of antiviral therapy and guide the precision treatment of patients.
- hepatitis B,chronic /
- HBV RNA /
- therapeutics

HTML全文

参考文献(25)

[1] URBAN S,SCHULZE A,DANDRI M,et al. The replication cycle of hepatitis B virus[J]. J Hepatol,2010,52(2):282-284.

[2] WANG J,SHEN T,HUANG X,et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound[J]. J Hepatol,2016,65(4):700-710.

[3] BLOCK TM,GUO H,GUO JT. Molecular virology of hepatitis B virus for clinicians[J]. Clin Liver Dis,2007,11(4):685-706.

[4] PRANGE R. Host factors involved in hepatitis B virus maturation,assembly,and egress[J]. Med Microbiol Immunol,2012,201(4):449-461.

[5] REGEV A,BERHO M,JEFFERS LJ,et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection[J]. Am J Gastroenterol,2002,97(10):2614-2618.

[6] ROUSSELET MC,MICHALAK S,DUPRF,et al. Sources of variability in histological scoring of chronic viral hepatitis[J].Hepatology,2005,41(2):257-264.

[7] SORIANO V,BARREIRO P,BENITEZ L,et al. New antivirals for the treatment of chronic hepatitis B[J]. Expert Opin Investig Drugs,2017,26(7):843-851.

[8] WANG J,DU M,HUANG H,et al. Reply to:“Serum HBV pgRNA as a clinical marker for cccDNA activity”:Consistent loss of serum HBV RNA might predict the “para-functional cure”of chronic hepatitis B[J]. J Hepatol,2017,66(2):462-463.

[9] WANG J,YU Y,LI G,et al. Relationship between serum HBV-RNA levels and intrahepatic viral as well as histologic activity markers in entecavir-treated patients[J]. J Hepatol,2018,68(1):16-24.

[10] GIERSCH K,ALLWEISS L,VOLZ T,et al. Serum HBV pgRNA as a clinical marker for cccDNA activity[J]. J Hepatol,2017,66(2):460-462.

[11] ALLWEISS L,LTGEHETMANN M,VOLZ T,et al. 42 pegylated-interferon-alpha alone or in combination with entecavir restores ISG responsiveness and reduces intrahepatic viral loads and antigenemia in hepatitis B virus infected humanized mice[J]. 2012,56(Suppl 2):s18-s19.

[12] BELLONI L,ALLWEISS L,GUERRIERI F,et al. IFN-αinhibits HBV transcription and replication in cell culture and in humanized mice by targeting the epigenetic regulation of the nuclear cccDNA minichromosome[J]. J Clin Invest,2012,122(2):529-537.

[13] WIELAND SF,EUSTAQUIO A,WHITTEN-BAUER C,et al.Interferon prevents formation of replication-competent hepatitis B virus RNA-containing nucleocapsids[J]. Proc Natl Acad Sci U S A,2005,102(28):9913-9917.

[14] HUANG YW,TAKAHASHI S,TSUGE M,et al. On-treatment low serum HBV RNA level predicts initial virological response in chronic hepatitis B patients receiving nucleoside analogue therapy[J]. Antivir Ther,2015,20(4):369-375.

[15] LIMOTHAI U,CHUAYPEN N,POOVORAWAN K,et al. Baseline and kinetics of serum hepatitis B virus RNA predict response to pegylated interferon-based therapy in patients with hepatitis B e antigen-negative chronic hepatitis B[J]. J Viral Hepat,2019,26(12):1481-1488.

[16] van BMMEL F,BARTENS A,MYSICKOVA A,et al. Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors[J]. Hepatology,2015,61(1):66-76.

[17] LUO H,TAN N,KANG Q,et al. Hepatitis B virus pregenomic RNA status can reveal the long-term prognoses of chronic hepatitis B patients treated with nucleos(t)ide analogues[J].J Viral Hepat,2020,27(3):323-328.

[18] JANSEN L,KOOTSTRA NA,van DORT KA,et al. Hepatitis B virus pregenomic RNA is present in virions in plasma and is associated with a response to pegylated interferon alfa-2a and nucleos(t)ide analogues[J]. J Infect Dis,2016,213(2):224-232.

[19] van BMMEL F,van BMMEL A,KRAUEL A,et al. Serum HBV RNA as a predictor of peginterferon alfa-2a response in patients with HBe Ag-positive chronic hepatitis B[J]. J Infect Dis,2018,218(7):1066-1074.

[20] JIA W,ZHU MQ,QI X,et al. Serum hepatitis B virus RNA levels as a predictor of HBe Ag seroconversion during treatment with peginterferon alfa-2a[J]. Virol J,2019,16(1):61.

[21] TSUGE M,MURAKAMI E,IMAMURA M,et al. Serum HBV RNA and HBe Ag are useful markers for the safe discontinuation of nucleotide analogue treatments in chronic hepatitis B patients[J]. J Gastroenterol,2013,48(10):1188-1204.

[22] FAN R,ZHOU B,XU M,et al. Association between negative results from tests for HBV DNA and RNA and durability of response after discontinuation of nucles(t)ide analogue therapy[J]. Clin Gastroenterol Hepatol,2020,18(3):719-727.

[23] ZHANG K,LIU Y,CHEN R,et al. Antigenicity reduction contributes mostly to poor detectability of HBs Ag by hepatitis B virus(HBV)S-gene mutants isolated from individuals with occult HBV infection[J]. J Med Virol,2018,90(2):263-270.

[24] KIM GA,LIM YS,AN J,et al. HBs Ag seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B:Clinical outcomes and durability[J]. Gut,2014,63(8):1325-1332.

[25] WANG J,CHEN X,WU Y,et al. Serum HBV RNA is a potential predictor of hepatitis B surface antigen reversion[J]. Hepatol Commun,2018,2(10):1168-1171.

施引文献

资源附件(0)

访问统计