血清HBV RNA在慢性乙型肝炎临床管理中的应用价值

廖昊; 王杰; 鲁凤民

doi:10.3969/j.issn.1001-5256.2019.10.003

血清HBV RNA在慢性乙型肝炎临床管理中的应用价值

DOI: 10.3969/j.issn.1001-5256.2019.10.003

1. 北京大学深圳医院深圳北京大学香港科技大学医学中心
2. 北京大学基础医学院病原生物学系暨感染病中心

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(2017ZX10302201)；国家自然科学基金(81672013)；

详细信息

中图分类号: R512.62
计量
- 文章访问数: 2456
- HTML全文浏览量: 47
- PDF下载量: 501
- 被引次数: 0
出版历程
- 收稿日期: 2019-08-01
- 出版日期: 2019-10-20

Application value of serum HBV RNA in clinical management of chronic hepatitis B

Peking University Shenzhen Hospital & Shenzhen PKU-HKUST Medical Center

Research funding:

摘要

摘要: 在我国,HBV感染所致病毒性肝炎、肝硬化、肝细胞癌等仍严重威胁我国公民的健康。积极的抗病毒治疗能够明显延缓肝脏疾病进程、减少终末期肝病的发生,但现有药物很难使患者临床治愈,特别是核苷(酸)类药物往往需要长期用药。新的血清学指标可以进一步优化抗病毒治疗方案,其中血清HBV RNA由肝组织内cccDNA转录,主要是未经或部分逆转录的前基因组RNA及其剪切变异体。总结了血清HBV RNA在HBV感染者血清中的存在形式和来源、影响其水平的因素、与其他血清病毒学指标的相关性、及其与肝组织cccDNA的关系,并评价了其在监测抗病毒疗效和预测停药后病毒反弹发生风险等方面的临床意义。
- 乙型肝炎病毒 /
- RNA /
- DNA,环状 /
- 抗病毒药
Abstract: Viral hepatitis,liver cirrhosis,and hepatocellular carcinoma caused by hepatitis B virus(HBV) infection still threaten the health of people in China. Efficient antiviral therapy can significantly prevent the progression of liver diseases and reduce the incidence rate of end-stage liver disease,but it is very difficult to achieve clinical cure by current drugs,and nucleos(t) ide analogues may require long-term medication. New serological markers can be used for further optimization of antiviral regimens,among which serum HBV RNA is transcribed from covalently closed circular DNA(cccDNA) and is mainly derived from pregenomic RNA and its splice variants with no or partial reverse transcription. This article summarizes the sources and existing forms of serum HBV RNA,the influencing factors for serum HBV RNA level,the correlation between serum HBV RNA and other serum virological markers,and the correlation between serum HBV RNA and cccDNA in liver tissue,as well as the clinical significance of serum HBV RNA in monitoring antiviral efficacy and predicting the risk of viral rebound after drug withdrawal.
- hepatitis B virus /
- RNA /
- DNA,circular /
- antiviral agents

HTML全文

参考文献(37)

[1] KCK J,THEILMANN L,GALLE P,et al. Hepatitis B virus nucleic acids associated with human peripheral blood mononuclear cells do not originate from replicating virus[J]. Hepatology,1996,23(3):405-413.

[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] 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.

[4] LAM AM,REN S,ESPIRITU C,et al. Hepatitis B virus capsid assembly modulators,but not nucleoside analogs,inhibit the production of extracellular pregenomic RNA and spliced RNA variants[J]. Antimicrob Agents Chemother,2017,61(8):e00680-17.

[5] PRAKASH K,RYDELL GE,LARSSON SB,et al. High serum levels of pregenomic RNA reflect frequently failing reverse transcription in hepatitis B virus particles[J]. Virol J,2018,15(1):86.

[6] BAI L,ZHANG X,KOZLOWSKI M,et al. Extracellular hepatitis B virus RNAs are heterogeneous in length and circulate as capsidantibody complexes in addition to virions in chronic hepatitis B patients[J]. J Virol,2018,92(24):e00798-18.

[7] CHEN J,WU M,WANG F,et al. Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy[J]. Sci Rep,2015,5:16459.

[8] KAIRAT A,BEERHEIDE W,ZHOU G,et al. Truncated hepatitis B virus RNA in human hepatocellular carcinoma:Its representation in patients with advancing age[J]. Intervirology,1999,42(4):228-237.

[9] ZHANG P,LIU F,GUO F,et al. Characterization of novel hepadnaviral RNA species accumulated in hepatoma cells treated with viral DNA polymerase inhibitors[J]. Antiviral Res,2016,131:40-48.

[10] WANG J,SHENG Q,DING Y,et al. HBV RNA virion-like particles produced under nucleos(t)ide analogues treatment are mainly replication-deficient[J]. J Hepatol,2018,68(4):847-849.

[11] BUTLER EK,GERSCH J,MCNAMARA A,et al. Hepatitis B virus serum DNA and RNA levels in nucleos(t)ide analog-treated or untreated patients during chronic and acute infection[J]. Hepatology,2018,68(6):2106-2117.

[12] WANG J,YU Y,LI G,et al. Natural history of serum HBVRNA in chronic HBV infection[J]. J Viral Hepat,2018,25(9):1038-1047.

[13] van CAMPENHOUT MJH,van BMMEL F,PFEFFERKORN M,et al. Host and viral factors associated with serum hepatitis B virus RNA levels among patients in need for treatment[J].Hepatology,2018,68(3):839-847.

[14] HUANG H,WANG J,LI W,et al. Serum HBV DNA plus RNA shows superiority in reflecting the activity of intrahepatic cccDNA in treatment-nave HBV-infected individuals[J]. J Clin Virol,2018,99-100:71-78.

[15] 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,2017,pii:S0168-8278(17)32261-4.

[16] 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.

[17] LIAO H,LIU Y,LI X,et al. Monitoring of serum HBV RNA,HBcrAg,HBs Ag and anti-HBc levels in patients during long-term nucleoside/nucleotide analogue therapy[J]. Antivir Ther,2019,24(2):105-115.

[18] 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.

[19] 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.

[20] 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.

[21] 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.

[22] LUO H,ZHANG XX,CAO LH,et al. Serum hepatitis B virus RNA is a predictor of HBe Ag seroconversion and virological response with entecavir treatment in chronic hepatitis B patients[J]. World J Gastroenterol,2019,25(6):719-728.

[23] HATAKEYAMA T,NOGUCHI C,HIRAGA N,et al. Serum HBV RNA is a predictor of early emergence of the YMDD mutant in patients treated with lamivudine[J]. Hepatology,2007,45(5):1179-1186.

[24] GANE EJ. Future anti-HBV strategies[J]. Liver Int,2017,37(Suppl 1):40-44.

[25] SORIANO V. Hot news:Hepatitis B gene therapy coming to age[J]. AIDS Rev,2018,20(2):125-127.

[26] LAM AM,ESPIRITU C,VOGEL R,et al. Preclinical characterization of NVR 3-778,a first-in-class capsid assembly modulator against hepatitis B virus[J]. Antimicrob Agents Chemother,2019,63(1)pii:e01734-18.

[27] YUEN MF,GANE EJ,KIM DJ,et al. Antiviral activity,safety,and pharmacokinetics of capsid assembly modulator NVR 3-778 in patients with chronic HBV infection[J]. Gastroenterology,2019,156(5):1392-1403.

[28] LAHLALI T,BERKE JM,VERGAUWEN K,et al. Novel potent capsid assembly modulators regulate multiple steps of the hepatitis B virus life cycle[J]. Antimicrob Agents Chemother,2018,62(10). pii:e00835-18.

[29] SARIN SK,KUMAR M,LAU GK,et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B:A 2015update[J]. Hepatol Int,2016,10(1):1-98.

[30] European Association for the Study of the Liver. EASL 2017Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol,2017,67(2):370-398.

[31] TERRAULT NA,LOK ASF,MCMAHON BJ,et al. Update on prevention,diagnosis,and treatment of chronic hepatitis B:AASLD 2018 hepatitis B guidance[J]. Hepatology,2018,67(4):1560-1599.

[32] Chinese Society of Hepatology and Chinese Society of Infectious Diseases,Chinese Medical Association. The guideline of prevention andtreatment for chronic hepatitis B:A 2015 update[J]. J Clin Hepatol,2015,31(12):1941-1960.(in Chinese)中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2015更新版)[J].临床肝胆病杂志,2015,31(12):1941-1960.

[33] 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.

[34] 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.

[35] LU F,WANG J,CHEN X,et al. Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide analogs[J]. Front Med,2017,11(4):502-508.

[36] LU FM,WANG J,CHEN XM,et al. The potential use of serum HBV RNA to guide the functional cure of chronic hepatitis B[J]. Chin J Hepatol,2017,25(2):105-110.(in Chinese)鲁凤民,王杰,陈香梅,等.乙型肝炎病毒RNA病毒样颗粒的发现及其对抗病毒治疗临床实践的潜在影响[J].中华肝脏病杂志,2017,25(2):105-110.

[37] LU FM,DOU XG,ZHANG WH,et al. Clinical significance of serum HBV RNA measurement in chronic hepatitis B patients[J]. J Clin Hepatol,2018,34(5):934-938.(in Chinese)鲁凤民,窦晓光,张文宏,等.慢性乙型肝炎患者血清HBV RNA检测的临床意义[J].临床肝胆病杂志,2018,34(5):934-938.

施引文献

资源附件(0)

访问统计