中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 38 Issue 12
Dec.  2022
Turn off MathJax
Article Contents

Influencing factors for low-level viremia and their dynamic changes in patients with chronic hepatitis B treated with nucleos(t)ide analogues for the first time

DOI: 10.3969/j.issn.1001-5256.2022.12.008
Research funding:

General Program of Jiangxi Natural Science Foundation (20192BAB205090)

More Information
  • Corresponding author: GE Shanfei, geshanfei2010@163.com (ORCID: 0000-0002-5917-5863)
  • Received Date: 2022-05-19
  • Accepted Date: 2022-06-23
  • Published Date: 2022-12-20
  •   Objective  To investigate the influencing factors for low-level viremia (LLV) and their dynamic changes in chronic hepatitis B (CHB) patients treated with nucleos(t)ide analogues (NAs) for the first time.  Methods  A retrospective analysis was performed for 78 CHB patients who attended Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, from November 2020 to March 2022 and received antiviral therapy with NAs for at least 12 months, and according to HBV DNA level during treatment, they were divided into sustained virologic response (SVR) group with 58 patients and LLV group with 20 patients. 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 or the Fisher's exact test was used for comparison of categorical data between two groups. The multivariate Logistic regression analysis was used to investigate the independent influencing factors for LLV and establish a predictive model, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive value of this model. The Kaplan-Meier method was used to analyze cumulative HBV DNA negative conversion rate, and the Log-rank test was used for comparison. The analysis of variance with repeated measures was used to analyze the differences in HBV DNA and HBsAg between the two groups or within each group at weeks 0, 12, 24, 36, and 48.  Results  Compare with the SVR group, the LLV group had significantly higher HBeAg positive rate (90.0% vs 48.3%, χ2=10.701, P=0.001), log(HBV DNA) value (7.26±1.46 vs 5.65±1.70, t=-4.178, P < 0.001), and log(HBsAg) value (4.53±0.86 vs 3.44±0.93, t=-4.813, P < 0.001) and significantly lower age [29 (26-34) vs 33 (30-43), Z=-2.751, P=0.009], alanine aminotransferase (ALT) [67.0 (54.0-122.0)U/L vs 111.0 (47.0-406.0)U/L, Z=-2.203, P=0.028], aspartate aminotransferase [43.5 (32.8-62.8) U/L vs 77.5 (35.0-213.0)U/L, Z=-2.466, P=0.014], and liver stiffness measurement [7.7 (6.3-8.5)kPa vs 8.9 (7.2-11.4)kPa, Z=-2.022, P=0.043]. The multivariate logistic regression analysis showed that baseline HBV DNA (odds ratio [OR]=2.365, 95% confidence interval [CI]: 1.220-4.587, P=0.011), HBsAg (OR=4.229, 95% CI: 1.098-16.287, P=0.036), and ALT (OR=0.965, 95% CI: 0.937-0.994, P=0.018) were independent influencing factors for LLV in CHB patients, and the predictive model of Logit(MLLV)=-8.668+1.441×lgHBsAg+0.598×lgHBV DNA-0.016×ALT was established based on these factors, which had a larger area under the ROC curve than HBV DNA, HBsAg, and ALT (0.931 vs 0.774/0.856/0.666), with a sensitivity of 85.00% and a specificity of 93.10% at the optimal cut-off value of 0.44. The CHB patients with baseline HBV DNA > 7.29 lgIU/mL or HBsAg > 4.38 lgIU/mL had a significantly lower DNA negative conversion rate than those with DNA ≤7.29 lgIU/mL or HBsAg ≤4.38 lgIU/mL (χ2=22.52 and 26.35, both P < 0.001). In the CHB patients, the highest reduction rates of HBV DNA and HBsAg were observed at weeks 12 and 24, respectively, and the LLV group had significantly higher levels of HBV DNA and HBsAg than the SVR group at weeks 0, 12, 24, 36, and 48 (HBV DNA: t=-4.084, -4.526, -5.688, -7.123, and -6.266, all P < 0.001; HBsAg: t=-4.652, -4.691, -4.952, -4.804, and -4.407, all P < 0.001).  Conclusion  For the CHB patients treated with NAs for the first time, those with high HBV DNA load, high HBsAg quantification, and low ALT level at baseline are more likely to develop LLV, and dynamic monitoring of these indices is of great significance to observe the onset of LLV.

     

  • loading
  • [1]
    HUTIN Y, NASRULLAH M, EASTERBROOK P, et al. Access to treatment for hepatitis B virus infection-worldwide, 2016[J]. MMWR Morb Mortal Wkly Rep, 2018, 67(28): 773-777. DOI: 10.15585/mmwr.mm6728a2.
    [2]
    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.
    [3]
    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.
    [4]
    KIM HJ, CHO YK, JEON WK, et al. Clinical characteristics of patients with chronic hepatitis B who developed genotypic resistance to entecavir: Real-life experience[J]. Clin Mol Hepatol, 2017, 23(4): 323-330. DOI: 10.3350/cmh.2017.0005.
    [5]
    SHIN SK, YIM HJ, KIM JH, et al. Partial virological response after 2 years of entecavir therapy increases the risk of hepatocellular carcinoma in patients with hepatitis B virus-associated cirrhosis[J]. Gut Liver, 2021, 15(3): 430-439. DOI: 10.5009/gnl20074.
    [6]
    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. e6. DOI: 10.1016/j.cgh.2020.03.001.
    [7]
    MAK LY, HUANG Q, WONG DK, et al. Residual HBV DNA and pgRNA viraemia is associated with hepatocellular carcinoma in chronic hepatitis B patients on antiviral therapy[J]. J Gastroenterol, 2021, 56(5): 479-488. DOI: 10.1007/s00535-021-01780-5.
    [8]
    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.
    [9]
    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.
    [10]
    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.
    [11]
    LI H, XU WT, DENG BC, et al. Research progress in the functional treatment of chronic hepatitis B with nucleoside (acid) analogues and pegylated interferon[J]. Clin J Med Offic, 2022, 50(9): 890-893. DOI: 10.16680/j.1671-3826.2022.09.04.

    李卉, 许文涛, 邓宝成, 等. 核苷(酸)类似物联合聚乙二醇干扰素功能性治愈慢性乙型肝炎研究进展[J]. 临床军医杂志, 2022, 50(9): 890-893. DOI: 10.16680/j.1671-3826.2022.09.04.
    [12]
    OGAWA E, NOMURA H, NAKAMUTA M, et al. Tenofovir alafenamide after switching from entecavir or nucleos(t)ide combination therapy for patients with chronic hepatitis B[J]. Liver Int, 2020, 40(7): 1578-1589. DOI: 10.1111/liv.14482.
    [13]
    AGARWAL K, BRUNETTO M, SETO WK, et al. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection[J]. J Hepatol, 2018, 68(4): 672-681. DOI: 10.1016/j.jhep.2017.11.039.
    [14]
    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.
    [15]
    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.
    [16]
    REVILL PA, CHISARI FV, BLOCK JM, et al. A global scientific strategy to cure hepatitis B[J]. Lancet Gastroenterol Hepatol, 2019, 4(7): 545-558. DOI: 10.1016/S2468-1253(19)30119-0.
    [17]
    WU IC, LAI CL, HAN SH, et al. Efficacy of entecavir in chronic hepatitis B patients with mildly elevated alanine aminotransferase and biopsy-proven histological damage[J]. Hepatology, 2010, 51(4): 1185-1189. DOI: 10.1002/hep.23424.
    [18]
    ZHANG Q, PENG H, LIU X, et al. Chronic hepatitis B infection with low level viremia correlates with the progression of the liver disease[J]. J Clin Transl Hepatol, 2021, 9(6): 850-859. DOI: 10.14218/JCTH.2021.00046.
    [19]
    BAO T, HU QG, YE J, et al. Value of HBsAg level in dynamic monitoring of disease progression in patients with chronic HBV infection[J]. J Clin Hepatol, 2017, 33(8): 1475-1478. DOI: 10.3969/j.issn.1001-5256.2017.08.012.

    鲍腾, 胡庆刚, 叶珺, 等. HBsAg水平在慢性HBV感染者疾病进展中的动态监测价值[J]. 临床肝胆病杂志, 2017, 33(8): 1475-1478. DOI: 10.3969/j.issn.1001-5256.2017.08.012.
    [20]
    SONG JC, MIN BY, KIM JW, et al. Pretreatment serum HBsAg-to-HBV DNA ratio predicts a virologic response to entecavir in chronic hepatitis B[J]. Korean J Hepatol, 2011, 17(4): 268-273. DOI: 10.3350/kjhep.2011.17.4.268.
    [21]
    LEE JM, AHN SH, KIM HS, et al. Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir[J]. Hepatology, 2011, 53(5): 1486-1493. DOI: 10.1002/hep.24221.
    [22]
    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.
    [23]
    LIM SG, PHYO WW, LING J, et al. Comparative biomarkers for HBsAg loss with antiviral therapy shows dominant influence of quantitative HBsAg (qHBsAg)[J]. Aliment Pharmacol Ther, 2021, 53(1): 172-182. DOI: 10.1111/apt.16149.
  • 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

    Figures(5)  / Tables(4)

    Article Metrics

    Article views (1679) PDF downloads(114) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return