中文｜English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 38 Issue 10
Oct.  2022
Turn off MathJax
Article Contents
Article Navigation >  Journal of Clinical Hepatology  > 2022  >  38(10): 2252-2259

Influencing factors for low-level viremia in patients with chronic hepatitis B or hepatitis B liver cirrhosis and its association with the progression of liver inflammation and liver fibrosis

DOI: 10.3969/j.issn.1001-5256.2022.10.011
  • 1.

    Qingdao University Medical College, Qingdao, Shandong 266021, China

  • 2a.

    Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China

  • 3b.

    Department of Infectious Diseases, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China

  • 4c.

    Department of Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China

Research funding:

National Natural Science Foundation of China (RZ1900014929)

More Information
  • Corresponding author: BIAN Cheng, jinbeibei@126.com(ORCID: 0000-0001-6719-5664)
  • Received Date: 2022-02-27
  • Accepted Date: 2022-03-30
  • Published Date: 2022-10-20
    Abstract
  •   Objective  To investigate the influencing factors for low-level viremia (LLV) in patients with chronic hepatitis B (CHB) or hepatitis B liver cirrhosis (LC) receiving antiviral therapy and the association of LLV with the progression of liver inflammation and liver fibrosis.  Methods  A total of 417 patients with CHB or LC who attended the outpatient service of liver diseases in The Affiliated Hospital of Qingdao University from July 1, 2020 to November 30, 2021 were enrolled, and all patients received oral administration of nucleos(t)ide analogues as antiviral therapy for ≥1 year and had an HBV DNA level of < 2000 IU/mL. According to the HBV DNA level, the patients were divided into LLV group (10 IU/mL ≤HBV DNA < 2000 IU/mL) and complete virologic response (CVR) group (HBV DNA < 10 IU/mL). The two groups were compared in terms of general data, virology, biochemistry, and liver fibrosis markers before and after antiviral therapy to investigate the influencing factors for LLV. Meanwhile, the degree of changes in liver inflammation and liver fibrosis markers after antiviral therapy was compared between the two groups to analyze the association of LLV with the progression of liver inflammation and liver fibrosis. The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kendall's tau-b method was used for correlation analysis, and a multivariate logistic regression analysis was used to investigate the influencing factors for LLV.  Results  Among the 417 patients with CHB or LC, 173 developed LLV, and the constituent ratio of LLV was 41.5%; the patients with 10 IU/mL≤HBV DNA < 1000 IU/mL accounted for 94.8%. The logistic regression analysis showed that positive HBeAg (odds ratio [OR]=3.009, 95%CI: 1.346-6.729, P=0.007), a family history of LC or HCC (OR=2.929, 95%CI: 1.344-6.383, P=0.007), and HBV DNA > 1.0×108 IU/mL (OR=10.790, 95%CI: 1.265-92.007, P=0.030) before antiviral therapy were risk factors for the development of LLV, while aspartate aminotransferase (AST) > 40 U/L (OR=0.355, 95%CI: 0.171-0.737, P=0.005) was a protective factor against LLV; positive HBeAg after antiviral therapy (OR=4.394, 95%CI: 1.962-9.841, P < 0.001) was still a risk factor for LLV, and course of antiviral therapy ≥2 years and < 3 years (OR=0.175, 95%CI: 0.046-0.674, P=0.010) and course of antiviral therapy ≥3 years (OR=0.170, 95%CI: 0.048-0.600, P=0.006) were protective factors against LLV. Compared with the LLV group, the CVR group had significantly greater changes in AST, alpha-fetoprotein (AFP), aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) (ΔAST, ΔAFP, ΔAPRI, and ΔFIB-4, respectively) (all P < 0.05). Correlation analysis showed that ΔAST (τ=-0.192, P= < 0.001), ΔAFP (τ=-0.192, P < 0.001), ΔAPRI (τ=-0.210, P=0.002), and ΔFIB-4 (τ=-0.202, P=0.003) were all negatively correlated with LLV.  Conclusion  A highly sensitive HBV DNA detection method helps with the early diagnosis of LLV. Strong antiviral therapy should be given to patients with a family history of LC or HCC, a high HBV DNA level, positive HBeAg, or a low AST level, and HBV DNA, AST, and HBeAg should be closely monitored to identify LLV as early as possible.

     

    • FullText(HTML)
  • loading
    • References(25)
  • [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. DOI: 10.1016/S2468-1253(18)30056-6.
    [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. 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.
    [3]
    SHEN JY, HE R, DENG HM, et al. Clinical efficacy of tenofovir in the treatment of chronic hepatitis B[J]. Int J Virol, 2021, 28(2): 154-157. DOI: 10.3760/cma.j.issn.1673-4092.2021.02.015.

    沈金勇, 何然, 邓红梅, 等. 替诺福韦治疗慢性乙型肝炎患者临床疗效分析[J]. 国际病毒学杂志, 2021, 28(2): 154-157. DOI: 10.3760/cma.j.issn.1673-4092.2021.02.015.
    [4]
    LU FM, FENG B, ZHENG SJ, et al. Current status of the research on low-level viremia in chronic hepatitis B patients receiving nucleos(t)ide analogues[J]. J Clin Hepatol, 2021, 37(6): 1268-1274. DOI: 10.3969/j.issn.1001-5256.2021.06.007.

    鲁凤民, 封波, 郑素军, 等. 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[J]. 临床肝胆病杂志, 2021, 37(6): 1268-1274. DOI: 10.3969/j.issn.1001-5256.2021.06.007.
    [5]
    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. DOI: 10.1002/hep.29800.
    [6]
    Chinese Society of Ultrasound in Medicine; Oncology Intervention Committee of Chinese Research Hospital Society; National Health Commission Capacity Building and Continuing Education Expert Committee on Ultrasonic Diagnosis. Guideline for ultrasonic diagnosis of liver diseases[J]. J Clin Hepatol, 2021, 37(8): 1770-1785. DOI: 10.3969/j.issn.1001-5256.2021.08.007.

    中华医学会超声医学分会, 中国研究型医院学会肿瘤介入专业委员会, 国家卫生和健康委员会能力建设和继续教育中心超声医学专家委员会. 肝病超声诊断指南[J]. 临床肝胆病杂志, 2021, 37(8): 1770-1785. DOI: 10.3969/j.issn.1001-5256.2021.08.007.
    [7]
    CHO YY, LEE JH, CHANG Y, et al. Comparison of overall survival between antiviral-induced viral suppression and inactive phase chronic hepatitis B patients[J]. J Viral Hepat, 2018, 25(10): 1161-1171. DOI: 10.1111/jvh.12927.
    [8]
    SUN Y, WU X, ZHOU J, et al. Persistent low level of hepatitis B virus promotes fibrosis progression during therapy[J]. Clin Gastroenterol Hepatol, 2020, 18(11): 2582-2591. DOI: 10.1016/j.cgh.2020.03.001.
    [9]
    LEE SB, JEONG J, PARK JH, et al. Low-level viremia and cirrhotic complications in patients with chronic hepatitis B according to adherence to entecavir[J]. Clin Mol Hepatol, 2020, 26(3): 364-375. DOI: 10.3350/cmh.2020.0012.
    [10]
    KIM JH, SINN DH, KANG W, et al. Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment[J]. Hepatology, 2017, 66(2): 335-343. DOI: 10.1002/hep.28916.
    [11]
    LU JH, YANG L, ZHAO ZX, et al. Comparative study of high sensitivity and conventional fluorescence quantitative PCR in the monitoring of antiviral efficacy in patients with chronic hepatitis B[J]. J Mol Diagn Ther, 2019, 11(5): 361-364. DOI: 10.3969/j.issn.1674-6929.2019.05.005.

    卢建华, 杨莉, 赵召霞, 等. 高敏与普通荧光定量PCR技术在慢乙肝患者抗病毒疗效监测中的对比研究[J]. 分子诊断与治疗杂志, 2019, 11(5): 361-364. DOI: 10.3969/j.issn.1674-6929.2019.05.005.
    [12]
    CHEN P, SUN YL, DENG X, et al. Clinical application value of high-sensitivity real-time PCR in low load viral hepatitis[J]. China Med Herald, 2020, 17(19): 151-155. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202019041.htm

    陈鹏, 孙玉良, 邓星, 等. 高灵敏度real-time PCR在低病毒载量病毒性肝病中的临床应用价值[J]. 中国医药导报, 2020, 17(19): 151-155. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202019041.htm
    [13]
    European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67(2): 370-398. DOI: 10.1016/j.jhep.2017.03.021.
    [14]
    WHO. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection[M]. Geneva: World Health Organization, 2015.
    [15]
    SARIN SK, KUMAR M, LAU GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update[J]. Hepatol Int, 2016, 10(1): 1-98. DOI: 10.1007/s12072-015-9675-4.
    [16]
    DENG DL, JIANG JN, SU MH, et al. Liver histological status and clinic outcome in HBeAg-negative chronic hepatitis B with low viral load[J]. Chin J Hepatol, 2020, 28(12): 1013-1017. DOI: 10.3760/cma.j.cn501113-20201028-00584.

    邓德丽, 江建宁, 苏明华, 等. HBeAg阴性低病毒载量慢性乙型肝炎患者的肝组织学状态与转归[J]. 中华肝脏病杂志, 2020, 28(12): 1013-1017. DOI: 10.3760/cma.j.cn501113-20201028-00584.
    [17]
    ZHANG Q, CAI DC, HU P, et al. Low-level viremia in nucleoside analog-treated chronic hepatitis B patients[J]. Chin Med J (Engl), 2021, 134(23): 2810-2817. DOI: 10.1097/CM9.0000000000001793.
    [18]
    CHEN H, FU JJ, LI L, et al. Influencing factors for low-level viremia in chronic hepatitis B patients treated with long-term entecavir antiviral therapy[J]. J Clin Hepatol, 2021, 37(3): 556-559. DOI: 10.3969/j.issn.1001-5256.2021.03.011.

    陈贺, 傅涓涓, 李丽, 等. 长期恩替卡韦经治慢性乙型肝炎患者低病毒血症的相关影响因素[J]. 临床肝胆病杂志, 2021, 37(3): 556-559. DOI: 10.3969/j.issn.1001-5256.2021.03.011.
    [19]
    European Association for the Study of the Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection[J]. J Hepatol, 2012, 57(1): 167-185. DOI: 10.1016/j.jhep.2012.02.010.
    [20]
    CHAN HL, FUNG S, SETO WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial[J]. Lancet Gastroenterol Hepatol, 2016, 1(3): 185-195. DOI: 10.1016/S2468-1253(16)30024-3.
    [21]
    BUTI M, GANE E, SETO WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial[J]. Lancet Gastroenterol Hepatol, 2016, 1(3): 196-206. DOI: 10.1016/S2468-1253(16)30107-8.
    [22]
    MARCELLIN P, GANE E, BUTI M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study[J]. Lancet, 2013, 381(9865): 468-475. DOI: 10.1016/S0140-6736(12)61425-1.
    [23]
    XU Y, ZHANG YG, WANG X, et al. Long-term antiviral efficacy of entecavir and liver histology improvement in Chinese patients with hepatitis B virus-related cirrhosis[J]. World J Gastroenterol, 2015, 21(25): 7869-7876. DOI: 10.3748/wjg.v21.i25.7869.
    [24]
    YOO EH, CHO HJ. Clinical response to long-term tenofovir monotherapy in Korean chronic hepatitis B patients[J]. Clin Chim Acta, 2017, 471: 308-313. DOI: 10.1016/j.cca.2017.06.019.
    [25]
    LOVETT GC, NGUYEN T, ISER DM, et al. Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience[J]. World J Hepatol, 2017, 9(1): 48-56. DOI: 10.4254/wjh.v9.i1.48.
    • 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

    Tables(10)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (413) PDF downloads(88) 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