中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 36 Issue 6
Jun.  2020
Turn off MathJax
Article Contents

Research advances in predictive markers for HBeAg seroconversion in chronic hepatitis B patients treated with nucleos( t) ide analogues

DOI: 10.3969/j.issn.1001-5256.2020.06.036
Research funding:

 

  • Received Date: 2020-01-15
  • Published Date: 2020-06-20
  • Nucleos( t) ide analogues( NAs) are effective inhibitors for HBV replication and have become the preferred antiviral regimen for most patients with chronic hepatitis B( CHB). HBeAg seroconversion is an important index used to evaluate the durability and efficacy of antiviral therapy in HBeAg-positive CHB patients. The search for biomarkers that can predict HBeAg clearance or seroconversion after NAs treatment plays an important role in the selection of antiviral drugs,the adjustment of treatment regimens,and the achievement of individualized treatment. This article reviews the value of related markers,including HBV DNA,HBV RNA,anti-HBc,and HBcrAg,in predicting HBeAg clearance or seroconversion in CHB patients treated with NAs.

     

  • loading
  • [1] Polaris Observatory Collaborators. Global prevalence,treatment,and prevention of hepatitis B virus infection in 2016:A modelling study[J]. Lancet Gastroenterol Hepatol,2018,3(6):383-403.
    [2] 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.(in Chinese)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.
    [3] Chinese Society of Infectious Disease,Chinese Society of Hepatology,Chinese Medical Association. The expert consensus on functional cure of chronic hepatitis B[J]. J Clin Hepatol,2019,35(8):1693-1701.(in Chinese)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.
    [4] YUEN MF,CHEN DS,DUSHEIKO GM,et al. Hepatitis B virus infection[J]. Nat Rev Dis Primers,2018,4:18035.
    [5] KOH C,ZHAO X,SAMALA N,et al. AASLD clinical practice guidelines:A critical review of scientific evidence and evolving recommendations[J]. Hepatology,2013,58(6):2142-2152.
    [6] YANG HI,LU SN,LIAW YF,et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma[J]. N Engl J Med,2002,347(3):168-174.
    [7] SHEN J,LIU J,LI C,et al. The prognostic significance of serum HBe Ag on the recurrence and long-term survival after hepatectomy for hepatocellular carcinoma:A propensity score matching analysis[J]. J Viral Hepat,2018,25(9):1057-1065.
    [8] WANG JL,DU XF,CHEN SL,et al. Histological outcome for chronic hepatitis B patients treated with entecavir vs lamivudinebased therapy[J]. World J Gastroenterol,2015,21(32):9598-9606.
    [9] KAYAASLAN B,AKINCI E,ARI A,et al. A long-term multicenter study:Entecavir versus Tenofovir in treatment of nucleos(t)ide analogue-naive chronic hepatitis B patients[J].Clin Res Hepatol Gastroenterol,2018,42(1):40-47.
    [10] PERRILLO RP,LAI CL,LIAW YF,et al. Predictors of HBe Ag loss after lamivudine treatment for chronic hepatitis B[J].Hepatology,2002,36(1):186-194.
    [11] ZEUZEM S,GANE E,LIAW YF,et al. Baseline characteristics and early on-treatment response predict the outcomes of 2years of telbivudine treatment of chronic hepatitis B[J]. J Hepatol,2009,51(1):11-20.
    [12] WONG GL,WONG VW,CHAN HY,et al. Undetectable HBV DNA at month 12 of entecavir treatment predicts maintained viral suppression and HBe Ag-seroconversion in chronic hepatitis B patients at 3 years[J]. Aliment Pharmacol Ther,2012,35(11):1326-1335.
    [13] PENG CY,HSIEH TC,HSIEH TY,et al. HBV-DNA level at 6months of entecavir treatment predicts HBe Ag loss in HBe Agpositive chronic hepatitis B patients[J]. J Formos Med Assoc,2015,114(4):308-313.
    [14] HUANG YJ,CHANG CS,PENG YC,et al. On-treatment HBV DNA level could predict HBe Ag seroclearance in patients with HBe Ag-positive chronic hepatitis B with entecavir therapy[J]. J Chin Med Assoc,2017,80(6):341-346.
    [15] 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.
    [16] 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.
    [17] 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.
    [18] 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.
    [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] 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.
    [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] YIN XR,SHE GX,HOU JL,et al. Clinical significance and application of quantification of hepatitis B core antibody[J]. J Clin Hepatol,2019,35(10):2156-2158.(in Chinese)尹雪如,佘格欣,侯金林,等.抗-HBc定量的临床意义与应用[J].临床肝胆病杂志,2019,35(10):2156-2158.
    [23] LI MR,LU JH,YE LH,et al. Quantitative hepatitis B core antibody level is associated with inflammatory activity in treatmentnave chronic hepatitis B patients[J]. Medicine(Baltimore),2016,95(34):e4422.
    [24] LI MR,ZHENG HW,LU JH,et al. Serum hepatitis B core antibody titer use in screening for significant fibrosis in treatmentnave patients with chronic hepatitis B[J]. Oncotarget,2017,8(7):11063-11070.
    [25] FAN R,SUN J,YUAN Q,et al. Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBe Ag seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues[J]. Gut,2016,65(2):313-320.
    [26] CAI S,LI Z,YU T,et al. Serum hepatitis B core antibody levels predict HBe Ag seroconversion in chronic hepatitis B patients with high viral load treated with nucleos(t)ide analogs[J]. Infect Drug Resist,2018,11:469-477.
    [27] 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.
    [28] XU JH,SONG LW,LI N,et al. Baseline hepatitis B core antibody predicts treatment response in chronic hepatitis B patients receiving long-term entecavir[J]. J Viral Hepat,2017,24(2):148-154.
    [29] ZOULIM F,CAROSI G,GREENBLOOM S,et al. Quantification of HBs Ag in nucleos(t)ide-nave patients treated for chronic hepatitis B with entecavir with or without tenofovir in the BE-LOW study[J]. J Hepatol,2015,62(1):56-63.
    [30] CHEN CH,LU SN,HUNG CH,et al. The role of hepatitis B surface antigen quantification in predicting HBs Ag loss and HBV relapse after discontinuation of lamivudine treatment[J].J Hepatol,2014,61(3):515-522.
    [31] 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.
    [32] YANG J,CHEN J,YE P,et al. HBs Ag as an important predictor of HBe Ag seroconversion following antiviral treatment for HBe Ag-positive chronic hepatitis B patients[J]. J Transl Med,2014,12:183.
    [33] SINGH AK,SHARMA MK,HISSAR SS,et al. Relevance of hepatitis B surface antigen levels in patients with chronic hepatitis B during 5 year of tenofovir treatment[J]. J Viral Hepat,2014,21(6):439-446.
    [34] MAK LY,WONG DK,CHEUNG KS,et al. Review article:Hepatitis B core-related antigen(HBcrAg):An emerging marker for chronic hepatitis B virus infection[J]. Aliment Pharmacol Ther,2018,47(1):43-54.
    [35] WONG DK,SETO WK,CHEUNG KS,et al. Hepatitis B virus core-related antigen as a surrogate marker for covalently closed circular DNA[J]. Liver Int,2017,37(7):995-1001.
    [36] CHEN EQ,TANG H. Hepatitis B virus core-related antigen:A promising new serum marker for hepatitis B virus[J]. J Clin Hepatol,2019,35(10):2159-2162.(in Chinese)陈恩强,唐红.一种有前途的新型HBV血清标志物———HBcrAg[J].临床肝胆病杂志,2019,35(10):2159-2162.
    [37] WANG ML,LIAO J,WEI B,et al. Comparison of hepatitis B virus core-related antigen and hepatitis B surface antigen for predicting HBe Ag seroconversion in chronic hepatitis B patients with pegylated interferon therapy[J]. Infect Dis(Lond),2018,50(7):522-530.
    [38] WANG B,CAREY I,BRUCE M,et al. HBsAg and HBcrAg as predictors of HBe Ag seroconversion in HBe Ag-positive patients treated with nucleos(t)ide analogues[J]. J Viral Hepat,2018,25(8):886-893.
    [39] LI C,JI H,CAI Y,et al. Serum interleukin-37 concentrations and HBe Ag seroconversion in chronic HBV patients during telbivudine treatment[J]. J Interferon Cytokine Res,2013,33(10):612-618.
    [40] GUO R,MAO H,HU X,et al. Slow reduction of IP-10 Levels predicts HBe Ag seroconversion in chronic hepatitis B patients with 5 years of entecavir treatment[J]. Sci Rep,2016,6:37015.
    [41] MA SW,HUANG X,LI YY,et al. High serum IL-21 levels after 12 weeks of antiviral therapy predict HBe Ag seroconversion in chronic hepatitis B[J]. J Hepatol,2012,56(4):775-781.
    [42] ZHENG Q,ZHU YY,CHEN J,et al. Decline in intrahepatic cccDNA and increase in immune cell reactivity after 12 weeks of antiviral treatment were associated with HBe Ag loss[J]. J Viral Hepat,2014,21(12):909-916.
    [43] 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.
  • 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

    Article Metrics

    Article views (555) PDF downloads(88) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return