中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 7
Jul.  2021
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(7): 1682-1685

Influencing factors for serum HBsAg clearance in people with chronic hepatitis B virus infection and its clinical significance

DOI: 10.3969/j.issn.1001-5256.2021.07.043
  • 1.

    Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China

  • 2.

    Graduate School of Tianjin Medical University, Tianjin 300070, China

  • 3.

    Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China

  • 4.

    Hepatology Institute, Peking University People's Hospital, Beijing 100044, China

Research funding:

The National S & T Major Project for Infectious Diseases (2017ZX10202202);

The National S & T Major Project for Infectious Diseases (2017ZX10202203)

  • Received Date: 2020-11-05
  • Accepted Date: 2021-01-25
  • Published Date: 2021-07-20
    Abstract
  • HBsAg clearance can significantly reduce the risk of end-stage liver disease and liver cancer in patients with chronic hepatitis B; however, HBsAg clearance rate is very low, either by spontaneous clearance or antiviral therapy. This article summarizes the influencing factors for spontaneous clearance of HBsAg and HBsAg clearance after antiviral therapy and the durability of HBsAg clearance. In addition, this article reviews the potential of new drugs in development, such as nucleic acid polymers and immunomodulators, in HBsAg clearance, so as to provide clues for the clinical cure of chronic hepatitis B in the future.

     

    • FullText(HTML)
  • loading
    • References(46)
  • [1]
    Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B(version 2019)[J]. J Clin Hepatol, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.

    中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.
    [2]
    Chinese Society of Infectious Disease, Chinese Society of Hepatology, Chinese Medical Association. The expert consensus on clinical cure (functional cure) of chronic hepatitis B[J]. J Clin Hepatol, 2019, 35(8): 1693-1701. DOI: 10.3969/j.issn.1001-5256.2019.08.008.

    中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎临床治愈(功能性治愈)专家共识[J]. 临床肝胆病杂志, 2019, 35(8): 1693-1701. DOI: 10.3969/j.issn.1001-5256.2019.08.008.
    [3]
    ALAWAD AS, AUH S, SUAREZ D, et al. Durability of spontaneous and treatment-related loss of hepatitis B s antigen[J]. Clin Gastroenterol Hepatol, 2020, 18(3): 700-709. e3. DOI: 10.1016/j.cgh.2019.07.018.
    [4]
    YIP TC, WONG GL, CHAN HL, et al. HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues[J]. J Hepatol, 2019, 70(3): 361-370. DOI: 10.1016/j.jhep.2018.10.014.
    [5]
    YIP TC, WONG GL, WONG VW, et al. Durability of hepatitis B surface antigen seroclearance in untreated and nucleos(t)ide analogue-treated patients[J]. J Hepatol, 2017. DOI: 10.1016/j.jhep.2017.09.018.[Online ahead of print]
    [6]
    KIM MA, KIM SU, SINN DH, et al. Discontinuation of nucleos(t)ide analogues is not associated with a higher risk of HBsAg seroreversion after antiviral-induced HBsAg seroclearance: A nationwide multicentre study[J]. Gut, 2020, 69(12): 2214-2222. DOI: 10.1136/gutjnl-2019-320015.
    [7]
    ZHOU K, CONTAG C, WHITAKER E, et al. Spontaneous loss of surface antigen among adults living with chronic hepatitis B virus infection: A systematic review and pooled meta-analyses[J]. Lancet Gastroenterol Hepatol, 2019, 4(3): 227-238. DOI: 10.1016/S2468-1253(18)30308-X.
    [8]
    YEO YH, HO HJ, YANG HI, et al. Factors associated with rates of HBsAg seroclearance in adults with chronic HBV infection: A systematic review and Meta-analysis[J]. Gastroenterology, 2019, 156(3): 635-646. e9. DOI: 10.1053/j.gastro.2018.10.027.
    [9]
    NGUYEN LH, HOANG J, NGUYEN NH, et al. Ethnic differences in incidence of hepatitis B surface antigen seroclearance in a real-life multicenter clinical cohort of 4737 patients with chronic hepatitis B infection[J]. Aliment Pharmacol Ther, 2016, 44(4): 390-399. DOI: 10.1111/apt.13709.
    [10]
    OLIVERI F, SURACE L, CAVALLONE D, et al. Long-term outcome of inactive and active, low viraemic HBeAg-negative-hepatitis B virus infection: Benign course towards HBsAg clearance[J]. Liver Int, 2017, 37(11): 1622-1631. DOI: 10.1111/liv.13416.
    [11]
    SHAH PA, KAUR S, SIMONS B, et al. Patterns of HBeAg and HBsAg clearance among a treatment-naive Alaskan Cohort in a long-term observational study[J]. J Viral Hepat, 2020, 27(6): 644-646. DOI: 10.1111/jvh.13271.
    [12]
    ILUZ-FREUNDLICH D, SAMAD N, MILES D, et al. Spontaneous flares of chronic hepatitis B virus in hepatitis be antigen negative carriers who subsequently clear hepatitis B surface antigen[J]. Dig Dis Sci, 2021, 66(1): 257-262. DOI: 10.1007/s10620-020-06125-5.
    [13]
    KIM JH, LEE JH, PARK SJ, et al. Factors associated with natural seroclearance of hepatitis B surface antigen and prognosis after seroclearance: A prospective follow-up study[J]. Hepatogastroenterology, 2008, 55(82-83): 578-581. http://www.ncbi.nlm.nih.gov/pubmed/18613411/
    [14]
    CHU CM, LIAW YF. HBsAg seroclearance in asymptomatic carriers of high endemic areas: Appreciably high rates during a long-term follow-up[J]. Hepatology, 2007, 45(5): 1187-1192. DOI: 10.1002/hep.21612.
    [15]
    CHEN YC, CHU CM, YEH CT, et al. Natural course following the onset of cirrhosis in patients with chronic hepatitis B: A long-term follow-up study[J]. Hepatol Int, 2007, 1(1): 267-273. DOI: 10.1007/s12072-007-5001-0.
    [16]
    LIU F, WANG XW, CHEN L, et al. Systematic review with meta-analysis: Development of hepatocellular carcinoma in chronic hepatitis B patients with hepatitis B surface antigen seroclearance[J]. Aliment Pharmacol Ther, 2016, 43(12): 1253-1261. DOI: 10.1111/apt.13634.
    [17]
    LIAW YF. Clinical utility of HBV surface antigen quantification in HBV e antigen-negative chronic HBV infection[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(10): 631-641. DOI: 10.1038/s41575-019-0197-8.
    [18]
    LIU J, LI T, ZHANG L, et al. The role of hepatitis B surface antigen in nucleos(t)ide analogues cessation among asian patients with chronic hepatitis B: A systematic review[J]. Hepatology, 2019, 70(3): 1045-1055. DOI: 10.1002/hep.30474.
    [19]
    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. DOI: 10.1111/jvh.13195.
    [20]
    YAN Y, ALLWEISS L, YANG D, et al. Down-regulation of cell membrane localized NTCP expression in proliferating hepatocytes prevents hepatitis B virus infection[J]. Emerg Microbes Infect, 2019, 8(1): 879-894. DOI: 10.1080/22221751.2019.1625728.
    [21]
    CAO Z, LIU Y, MA L, et al. A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha[J]. Hepatology, 2017, 66(4): 1058-1066. DOI: 10.1002/hep.29213.
    [22]
    WONG D, LITTLEJOHN M, EDWARDS R, et al. ALT flares during nucleotide analogue therapy are associated with HBsAg loss in genotype A HBeAg-positive chronic hepatitis B[J]. Liver Int, 2018, 38(10): 1760-1769. DOI: 10.1111/liv.13716.
    [23]
    BERG T, SIMON KG, MAUSS S, et al. Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients - FINITE study[J]. J Hepatol, 2017, 67(5): 918-924. DOI: 10.1016/j.jhep.2017.07.012.
    [24]
    LIAW YF. Hepatitis B flare after cessation of nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B: To retreat or not to retreat[J]. Hepatology, 2021, 73(2): 843-852. DOI: 10.1002/hep.31525.
    [25]
    PEPPA D, GILL US, REYNOLDS G, et al. Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion[J]. J Exp Med, 2013, 210(1): 99-114. DOI: 10.1084/jem.20121172.
    [26]
    DONG Y, CHEN H, GAO J, et al. Molecular machinery and interplay of apoptosis and autophagy in coronary heart disease[J]. J Mol Cell Cardiol, 2019, 136: 27-41. DOI: 10.1016/j.yjmcc.2019.09.001.
    [27]
    WANG H, LUO H, WAN X, et al. TNF-α/IFN-γ profile of HBV-specific CD4 T cells is associated with liver damage and viral clearance in chronic HBV infection[J]. J Hepatol, 2020, 72(1): 45-56. DOI: 10.1016/j.jhep.2019.08.024.
    [28]
    LOOMBA R, LIANG TJ. Hepatitis B reactivation associated with immune suppressive and biological modifier therapies: Current concepts, management strategies, and future directions[J]. Gastroenterology, 2017, 152(6): 1297-1309. DOI: 10.1053/j.gastro.2017.02.009.
    [29]
    OLIVIERO B, CERINO A, VARCHETTA S, et al. Enhanced B-cell differentiation and reduced proliferative capacity in chronic hepatitis C and chronic hepatitis B virus infections[J]. J Hepatol, 2011, 55(1): 53-60. DOI: 10.1016/j.jhep.2010.10.016.
    [30]
    ZIMMER CL, RINKER F, HÖNER ZU SIEDERDISSEN C, et al. Increased NK cell function after cessation of long-term nucleos(t)ide analogue treatment in chronic hepatitis B is associated with liver damage and HBsAg loss[J]. J Infect Dis, 2018, 217(10): 1656-1666. DOI: 10.1093/infdis/jiy097.
    [31]
    PEPPA D, GILL US, REYNOLDS G, et al. Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion[J]. J Exp Med, 2013, 210(1): 99-114. DOI: 10.1084/jem.20121172.
    [32]
    LI H, ZHAI N, WANG Z, et al. Regulatory NK cells mediated between immunosuppressive monocytes and dysfunctional T cells in chronic HBV infection[J]. Gut, 2018, 67(11): 2035-2044. DOI: 10.1136/gutjnl-2017-314098.
    [33]
    MICHLER T, KOSINSKA AD, FESTAG J, et al. Knockdown of virus antigen expression increases therapeutic vaccine efficacy in high-titer hepatitis B virus carrier mice[J]. Gastroenterology, 2020, 158(6): 1762-1775. e9. DOI: 10.1053/j.gastro.2020.01.032.
    [34]
    NING Q, WU D, WANG GQ, et al. Roadmap to functional cure of chronic hepatitis B: An expert consensus[J]. J Viral Hepat, 2019, 26(10): 1146-1155. DOI: 10.1111/jvh.13126.
    [35]
    LIU J, WANG T, ZHANG W, et al. Effect of combination treatment based on interferon and nucleos(t)ide analogues on functional cure of chronic hepatitis B: A systematic review and meta-analysis[J]. Hepatol Int, 2020, 14(6): 958-972. DOI: 10.1007/s12072-020-10099-x.
    [36]
    VAILLANT A. REP 2139: Antiviral mechanisms and applications in achieving functional control of HBV and HDV infection[J]. ACS Infect Dis, 2019, 5(5): 675-687. DOI: 10.1021/acsinfecdis.8b00156.
    [37]
    BAZINET M, PÂNTEA V, PLACINTA G, et al. Safety and efficacy of 48 weeks REP 2139 or REP 2165, tenofovir disoproxil, and pegylated interferon alfa-2a in patients with chronic HBV infection naïve to nucleos(t)ide therapy[J]. Gastroenterology, 2020, 158(8): 2180-2194. DOI: 10.1053/j.gastro.2020.02.058.
    [38]
    YUEN MF, GANE E, KIM DJ, et al. AS069-RO7062931 antisense oligonucleotide phase 1 study demonstrates target engagement in patients with chronic hepatitis B on established nucleos(t)ide therapy[J]. J Hepatol, 2020, 73(Suppl 1): s51. DOI: 10.1016/S0168-8278(20)30648-6.
    [39]
    GANE E, LOCARNINI S, LIM TH, et al. GS10-Short-term treatment with RNA interference therapy, JNJ-3989, results in sustained hepatitis B surface antigen supression in patients with chronic hepatitis B receiving nucleos(t)ide analogue treatment[J]. J Hepatol, 2020, 73(Suppl 1): s20. DOI: 10.1016/S0168-8278(20)30597-3.
    [40]
    GUPTA SV, FANGET MC, BAKARDJIEV A, et al. SAT462-Pharmacokinetics of VIR-2218, an RNAi therapeutic for the treatment of HBV infection, in healthy volunteers[J]. J Hepatol, 2020, 73(Suppl 1): s885. DOI: 10.1016/S0168-8278(20)32207-8.
    [41]
    CHEN D, KIM S, BROOKS A, et al. FRI350-Potential biomarkers of response in chronic hepatitis B patients who achieved HBeAg loss upon treatment with toll-like receptor 8 (TLR8) agonist selgantolimod[J]. J Hepatol, 2020, 73(Suppl 1): s571-s572. DOI: 10.1016/S0168-8278(20)31616-0.
    [42]
    HAGUE RM, HINE D, FERGUSSON J, et al. SAT458 - Immtav, a novel immunotherapy approach to eliminate hepatitis B virus[J]. J Hepatol, 2020, 73(Suppl 1): s882. 10.1016/S0168-8278(20)32203-0. http://www.sciencedirect.com/science/article/pii/S0168827820322030
    [43]
    WU Y, LIU Y, LU J, et al. Durability of interferon-induced hepatitis B surface antigen seroclearance[J]. Clin Gastroenterol Hepatol, 2020, 18(2): 514-516. e2. DOI: 10.1016/j.cgh.2019.04.020.
    [44]
    LI MH, YI W, ZHANG L, et al. Predictors of sustained functional cure in hepatitis B envelope antigen-negative patients achieving hepatitis B surface antigen seroclearance with interferon-alpha-based therapy[J]. J Viral Hepat, 2019, 26(Suppl 1): 32-41. DOI: 10.1111/jvh.13151.
    [45]
    WU Y, WANG X, LIN X, et al. Quantitative of serum hepatitis B core antibody is a potential predictor of recurrence after interferon-induced hepatitis B surface antigen clearance[J]. J Microbiol Immunol Infect, 2021, 54(2): 238-244. DOI: 10.1016/j.jmii.2019.09.004.
    [46]
    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]. J Chin Hepatol, 2017, 25(2): 105-110. DOI: 10.3760/cma.j.issn.1007-3418.2017.02.005.

    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. DOI: 10.3760/cma.j.issn.1007-3418.2017.02.005.
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索
    Get Citation
    PDF
    XML

    Article Metrics

    Article views (732) PDF downloads(128) Cited by()
    Proportional views
    Related
        

    The first journal specializing in hepatobiliary and pancreatic diseases in China

    Supervisor：Ministry of Education of the People's Republic of China

    Sponsor：Jilin University

    Academic Support: Chinese Society of Hepatology，Chinese Medical Association

    Address: 461 Xinjiang Road, Changchun

    Submit：0431-88782044

    Peer review：0431-88783542

    Email：lcgdb@vip.163.com

    About Journal

    Submission Guideline

    Journal Online

    Hepatobiliary College

    Guidelines

    YesterdayIP[]YesterdayPV[]TodayIP[]TodayPV[]Online[]

    Website Design © 2020 Editorial Board of Journal of Clinical Hepatology 吉ICP备10000617号-1 Supported by: Beijing Renhe Information Technology Co. Ltd  

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return