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ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 41 Issue 4
Apr.  2025
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Article Navigation >  Journal of Clinical Hepatology  > 2025  >  41(4): 736-741

Challenges and strategies for clinical treatment of low-level viremia in chronic hepatitis B patients

DOI: 10.12449/JCH250420

  • Department of Gastroenterology，Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine，Shanghai 200082，China

Research funding:

National Natural Science Foundation of China (82170617);

2023 Xinyi Digestive Disease Research Fund from the School of Gastroenterology, School of Medicine, Shanghai Jiao Tong University (KY-2023-04-02)

More Information
  • Corresponding author: LI Guangming， liguangming@xinhuamed.com.cn （ORCID： 0000-0001-9105-6867）
  • Received Date: 2024-07-27
  • Accepted Date: 2024-10-29
  • Published Date: 2025-04-25
    Abstract
  • Hepatitis B virus （HBV） infection is a global public health issue， affecting the health of 250 million people worldwide. Despite the significant progress in antiviral therapy for HBV， some patients still experience low-level viremia （LLV） after receiving antiviral therapy and fail to achieve viral clearance， with an HBV DNA load remaining at a relatively low level of 20 — 2 000 IU/mL. LLV is often caused by multiple factors such as the high stability of the virus， the difficulty in clearing the virus with antiviral drugs， host immune factors， and drug resistance， which increase the difficulties in antiviral therapy. In addition， LLV can also cause liver damage， which may eventually progress to severe outcomes such as hepatocellular carcinoma. This article reviews LLV in hepatitis B in terms of diagnosis， influencing factors， clinical significance， and treatment strategies.

     

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    • References(39)
  • [1]
    BURKI T. WHO’s 2024 global hepatitis report[J]. Lancet Infect Dis, 2024, 24( 6): e362- e363. DOI: 10.1016/S1473-3099(24)00307-4.
    [2]
    Polaris Observatory Collaborators. Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: A modelling study[J]. Lancet Gastroenterol Hepatol, 2023, 8( 10): 879- 907. DOI: 10.1016/S2468-1253(23)00197-8.
    [3]
    CUI FQ, BLACH S, MANZENGO MINGIEDI C, et al. Global reporting of progress towards elimination of hepatitis B and hepatitis C[J]. Lancet Gastroenterol Hepatol, 2023, 8( 4): 332- 342. DOI: 10.1016/S2468-1253(22)00386-7.
    [4]
    PATTYN J, HENDRICKX G, VORSTERS A, et al. Hepatitis B vaccines[J]. J Infect Dis, 2021, 224(12 suppl 2): S343- S351. DOI: 10.1093/infdis/jiaa668.
    [5]
    KAO JH. Hepatitis B vaccination and prevention of hepatocellular carcinoma[J]. Best Pract Res Clin Gastroenterol, 2015, 29( 6): 907- 917. DOI: 10.1016/j.bpg.2015.09.011.
    [6]
    CHIEN RN, LIAW YF. Current trend in antiviral therapy for chronic hepatitis B[J]. Viruses, 2022, 14( 2): 434. DOI: 10.3390/v14020434.
    [7]
    MIAO L, JIA CH, CHEN HD, et al. Study on the influencing factors of liver fibrosis reversal after entecavir treatment for chronic hepatitis B[J]. Clin J Med Offic, 2024, 52( 2): 176- 179. DOI: 10.16680/j.1671-3826.2024.02.17.

    苗亮, 贾春辉, 陈寒冬, 等. 恩替卡韦治疗慢性乙型肝炎获得病毒学应答后肝纤维化逆转影响因素研究[J]. 临床军医杂志, 2024, 52( 2): 176- 179. DOI: 10.16680/j.1671-3826.2024.02.17.
    [8]
    DENG W, JIANG TT, BI XY, et al. Progress on the treatment of chronic hepatitis B with interferons[J/CD]. Chin J Liver Dis(Electronic Version), 2023, 15( 2): 1- 6.

    邓雯, 蒋婷婷, 毕潇月, 等. 干扰素治疗慢性乙型肝炎研究进展[J/CD]. 中国肝脏病杂志(电子版), 2023, 15( 2): 1- 6.
    [9]
    XIONG DP, ZHAO WF. Functional cure of chronic hepatitis B[J]. Int J Epidemiol Infect Dis, 2023, 50( 6): 416- 421. DOI: 10.3760/cma.j.cn331340-20230420-00065.

    熊丹萍, 赵卫峰. 慢性乙型肝炎的功能性治愈[J]. 国际流行病学传染病学杂志, 2023, 50( 6): 416- 421. DOI: 10.3760/cma.j.cn331340-20230420-00065.
    [10]
    SINN DH, KIM SE, KIM BK, et al. The risk of hepatocellular carcinoma among chronic hepatitis B virus-infected patients outside current treatment criteria[J]. J Viral Hepat, 2019, 26( 12): 1465- 1472. DOI: 10.1111/jvh.13185.
    [11]
    YANG J, CHOI WM, SHIM JH, et al. Low level of hepatitis B viremia compared with undetectable viremia increases the risk of hepatocellular carcinoma in patients with untreated compensated cirrhosis[J]. Am J Gastroenterol, 2023, 118( 6): 1010- 1018. DOI: 10.14309/ajg.0000000000002181.
    [12]
    XIE L, LIU YN, LIU GW, et al. Incidence rate of low-level viremia and related influencing factors in treatment-experienced chronic hepatitis B patients: A Meta-analysis[J]. J Clin Hepatol, 2024, 40( 7): 1334- 1342. DOI: 10.12449/JCH240709.

    谢露, 刘亚楠, 刘光伟, 等. 经治慢性乙型肝炎患者低病毒血症发生率和影响因素的Meta分析[J]. 临床肝胆病杂志, 2024, 40( 7): 1334- 1342. DOI: 10.12449/JCH240709.
    [13]
    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.
    [14]
    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.
    [15]
    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.
    [16]
    Chinese Society of Hepatology, Chinese Society of Infectious Diseases. Guidelines for the prevention and treatment of chronic hepatitis B(2022 version)[J]. Chin J Infect Dis, 2023, 41( 1): 3- 28. DOI: 10.3760/cma.j.cn311365-20230220-00050.

    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(2022年版)[J]. 中华传染病杂志, 2023, 41( 1): 3- 28. DOI: 10.3760/cma.j.cn311365-20230220-00050.
    [17]
    SHI YJ, DING Y, AO L, et al. Very low-level viremia: New clinical attention-requiring problem during the course of anti-hepatitis B virus treatment[J]. Chin J Hepatol, 2021, 29( 12): 1147- 1150. DOI: 10.3760/cma.j.cn501113-20210830-00442.

    石宇婧, 丁银, 敖玲, 等. 极低病毒血症: 抗乙型肝炎病毒治疗过程中需要关注的临床新问题[J]. 中华肝脏病杂志, 2021, 29( 12): 1147- 1150. DOI: 10.3760/cma.j.cn501113-20210830-00442.
    [18]
    DUAN MH, CHI XL, XIAO HM, et al. High-normal alanine aminotransferase is an indicator for liver histopathology in HBeAg-negative chronic hepatitis B[J]. Hepatol Int, 2021, 15( 2): 318- 327. DOI: 10.1007/s12072-021-10153-2.
    [19]
    LEE HW, PARK SY, LEE YR, et al. Episodic detectable viremia does not affect prognosis in untreated compensated cirrhosis with serum hepatitis B virus DNA<2 000 IU/mL[J]. Am J Gastroenterol, 2022, 117( 2): 288- 294. DOI: 10.14309/ajg.0000000000001497.
    [20]
    WEI L, PLOSS A. Mechanism of hepatitis B virus cccDNA formation[J]. Viruses, 2021, 13( 8): 1463. DOI: 10.3390/v13081463.
    [21]
    LIU YZ, LIU H, HU ZY, et al. Hepatitis B virus virions produced under nucleos(t)ide analogue treatment are mainly not infectious because of irreversible DNA chain termination[J]. Hepatology, 2020, 71( 2): 463- 476. DOI: 10.1002/hep.30844.
    [22]
    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.
    [23]
    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.
    [24]
    WONG GLH, WONG VWS, CHAN HY, et al. Undetectable HBV DNA at month 12 of entecavir treatment predicts maintained viral suppression and HBeAg-seroconversion in chronic hepatitis B patients at 3 years[J]. Aliment Pharmacol Ther, 2012, 35( 11): 1326- 1335. DOI: 10.1111/j.1365-2036.2012.05098.x.
    [25]
    DUAN SH, YUAN XD, LIU XY, et al. Clinical observation of continuous and intermittent application of lamivudine or entecavir resistance mutations in patients with chronic hepatitis B[J]. Chin J Hepatol, 2018, 26( 9): 646- 649. DOI: 10.3760/cma.j.issn.1007-3418.2018.09.002.

    段淑红, 苑晓冬, 刘晓燕, 等. 持续及间断应用拉米夫定或恩替卡韦治疗慢性乙型肝炎出现病毒耐药变异概率的临床观察[J]. 中华肝脏病杂志, 2018, 26( 9): 646- 649. DOI: 10.3760/cma.j.issn.1007-3418.2018.09.002.
    [26]
    WANG FS, ZHANG Z. Host immunity influences disease progression and antiviral efficacy in humans infected with hepatitis B virus[J]. Expert Rev Gastroenterol Hepatol, 2009, 3( 5): 499- 512. DOI: 10.1586/egh.09.50.
    [27]
    LIAW YF, CHU CM. Hepatitis B virus infection[J]. Lancet, 2009, 373( 9663): 582- 592. DOI: 10.1016/S0140-6736(09)60207-5.
    [28]
    WANG LJ, GU ZQ, XU ZM, et al. A possible mechanism for low-level viremia occurrence in nucleos(t)ide analog-treated chronic hepatitis B patients[J]. Chin J Hepatol, 2021, 29( 12): 1151- 1155. DOI: 10.3760/cma.j.cn501113-20211124-00578.

    王雷婕, 顾智强, 许梓萌, 等. 核苷(酸)类药物经治慢性乙型肝炎患者低病毒血症发生的可能机制[J]. 中华肝脏病杂志, 2021, 29( 12): 1151- 1155. DOI: 10.3760/cma.j.cn501113-20211124-00578.
    [29]
    YAN MM, SUN LH. Natural history of chronic hepatitis B virus infection under low-level viremia[J]. Chin J Hepatol, 2023, 31( 3): 322- 326. DOI: 10.3760/cma.j.cn501113-20220907-00461.

    严梅梅, 孙丽华. 自然状态下乙型肝炎病毒慢性感染中的低病毒血症[J]. 中华肝脏病杂志, 2023, 31( 3): 322- 326. DOI: 10.3760/cma.j.cn501113-20220907-00461.
    [30]
    LI T, KONG Y, LIU YY, et al. Demographic characteristics and associated influencing factors in treated patients with chronic hepatitis B with hypoviremia: A single-center retrospective cross-sectional study[J]. Chin J Hepatol, 2023, 31( 1): 42- 48. DOI: 10.3760/cma.j.cn501113-20220121-00039.

    李彤, 孔银, 刘元元, 等. 经治慢性乙型肝炎低病毒血症患者人群特征及其相关影响因素: 一项单中心横断面回顾性研究[J]. 中华肝脏病杂志, 2023, 31( 1): 42- 48. DOI: 10.3760/cma.j.cn501113-20220121-00039.
    [31]
    HUANG YX, CHEN XY, LI Z. Variation of hepatitis B virus and its significance[J]. Int J Virol, 2006, 13( 4): 100- 104. DOI: 10.3760/cma.j.issn.1673-4092.2006.04.002.

    黄雁翔, 陈新月, 李卓. 乙型肝炎病毒变异及其意义[J]. 国际病毒学杂志, 2006, 13( 4): 100- 104. DOI: 10.3760/cma.j.issn.1673-4092.2006.04.002.
    [32]
    ZHANG Q, PENG H, LIU XQ, 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.
    [33]
    SUN YM, WU XN, ZHOU JL, et al. Persistent low level of hepatitis B virus promotes fibrosis progression during therapy[J]. Clin Gastroenterol Hepatol, 2020, 18( 11): 2582- 2591. e 6. DOI: 10.1016/j.cgh.2020.03.001.
    [34]
    HUANG X, YAN MM, DENG ZR, et al. Natural history of decompensated cirrhosis with serum hepatitis B DNA<2 000 IU/mL: A retrospective study[J]. BMC Gastroenterol, 2022, 22( 1): 452. DOI: 10.1186/s12876-022-02541-1.
    [35]
    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.
    [36]
    JANG JW, CHOI JY, KIM YS, et al. Effects of virologic response to treatment on short- and long-term outcomes of patients with chronic hepatitis B virus infection and decompensated cirrhosis[J]. Clin Gastroenterol Hepatol, 2018, 16( 12): 1954- 1963. e 3. DOI: 10.1016/j.cgh.2018.04.063.
    [37]
    XIE YD, FENG B, RAO HY. Interpretation of guidelines for the prevention and treatment of chronic hepatitis B(2022 edition)[J]. J Clin Hepatol, 2023, 39( 7): 1553- 1559. DOI: 10.3969/j.issn.1001-5256.2023.07.007.

    谢艳迪, 封波, 饶慧瑛.《慢性乙型肝炎防治指南(2022年版)》解读[J]. 临床肝胆病杂志, 2023, 39( 7): 1553- 1559. DOI: 10.3969/j.issn.1001-5256.2023.07.007.
    [38]
    LI ZB, LI L, NIU XX, et al. Switching from entecavir to tenofovir alafenamide for chronic hepatitis B patients with low-level viraemia[J]. Liver Int, 2021, 41( 6): 1254- 1264. DOI: 10.1111/liv.14786.
    [39]
    YAN L, ZHU CW, LI J, et al. Entecavir add-on or switch-to pegylated interferon improves HBsAg clearance in HBe antigen negative chronic hepatitis B patients[J]. Infect Drug Resist, 2018, 11: 2001- 2009. DOI: 10.2147/IDR.S175707.
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