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Volume 42 Issue 1
Jan.  2026
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Article Navigation >  Journal of Clinical Hepatology  > 2026  >  42(1): 66-73

Efficacy and safety of sequential or combined therapy with tenofovir alafenamide fumarate in entecavir-treated patients with low-level viremia

DOI: 10.12449/JCH260108
  • 1.

    Department of Pharmacy，Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 201203，China

  • 2.

    Department of Hepatopathy，Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 201203，China

  • 3.

    Laboratory of Cellular Immunity，Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 201203，China

Research funding:

National Natural Science Foundation of China (82574929);

National Natural Science Foundation of China (82274467);

High Level Key Disciplines of Medicine of National Administration of Traditional Chinese Medicine (ZYYZDXK-2023060);

Shanghai Municipal Health Commission Traditional Chinese Medicine Research Project (2024QN006);

Shanghai Science and Technology Innovation Action Plan (23Y21920200)

More Information
  • Corresponding author: GAO Yueqiu， gaoyueqiu@shutcm.edu.cn （ORCID： 0000-0001-7276-9810）
  • Received Date: 2025-08-12
  • Accepted Date: 2025-11-05
  • Published Date: 2026-01-25
    Abstract
  •   Objective  To investigate the efficacy of sequential tenofovir alafenamide fumarate （TAF） therapy versus the regimen of entecavir （ETV） combined with TAF in chronic hepatitis B （CHB） patients experiencing low-level viremia （LLV） after ETV therapy， as well as their impact on virologic response， liver and renal function， and blood lipid levels.  Methods  A total of 217 CHB patients with LLV after ETV treatment who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2020 to December 2023 were enrolled， and according to the treatment regimen， they were divided into TAF group （180 patients receiving sequential TAF therapy） and combined group （37 patients receiving ETV+TAF therapy）. The propensity score matching （PSM） method was used to match the patients at a ratio of 1∶1， and finally 37 patients were included in each group to balance the baseline confounding factors. The two groups were compared in terms of hepatitis B virus DNA （HBV DNA） clearance rate， hepatitis B envelope antigen （HBeAg） clearance rate， liver and renal function parameters （liver stiffness measurement ［LSM］， platelet count ［PLT］， aspartate aminotransferase ［AST］， alanine aminotransferase ［ALT］， and creatinine ［Cr］）， blood lipid levels （total cholesterol ［TC］， triglyceride ［TG］， high-density lipoprotein cholesterol ［HDL-C］， and low-density lipoprotein cholesterol ［LDL-C］）， and the incidence rate of adverse reactions. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the paired t-test was used for comparison within each group； the chi-square test was used for comparison of categorical data between groups.  Results  After 48 weeks of treatment， compared with the TAF group， the combined group had significantly higher HBV DNA clearance rate （86.49% vs 59.46%， χ²=6.852， P=0.009） and HBeAg clearance rate （59.46% vs 35.14%， χ²=4.391， P=0.036）. After treatment， compared with the TAF group， the combined group had significantly lower levels of LSM （7.01±1.50 kPa vs 7.90±1.68 kPa， t=2.404， P=0.019）， AST （18.02±2.28 U/L vs 21.12±2.85 U/L， t=5.166， P<0.001）， and ALT （19.85±3.86 U/L vs 22.00±3.90 U/L， t=2.383， P=0.020） and significantly higher levels of PLT ［（218.35±42.60）×109/L vs （192.82±44.13）×109/L， t=2.532， P=0.014］ and Cr （70.92±6.54 μmoL/L vs 67.60±6.13 μmoL/L， t=2.253， P=0.027）. After treatment， there was a slight increase in the level of TC in both the TAF group （5.60±0.89 mmol/L vs 5.18±0.85 mmol/L， t=2.076， P=0.041） and the combined group （5.45±0.80 mmol/L vs 5.02±0.83 mmol/L， t=2.269， P=0.026）. There was no significant difference in the incidence rate of adverse reactions between the TAF group and the combined group （21.62% vs 18.92%， χ²=0.084， P=0.772）.  Conclusion  For ETV-treated CHB patients experiencing LLV， compared with sequential TAF therapy， the ETV+TAF combined therapy can effectively increase virologic response rate， alleviate liver fibrosis， and improve liver function， whereas sequential TAF therapy has less impact on renal function. Sequential or combined therapy with TAF may induce a slight increase in the level of TC， which should be taken seriously in clinical practice.

     

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    • References(32)
  • [1]
    GUVENIR M, ARIKAN A. Hepatitis B virus: From diagnosis to treatment[J]. Pol J Microbiol, 2020, 69( 4): 391- 399. DOI: 10.33073/pjm-2020-044.
    [2]
    WONG GL, LEMOINE M. The 2024 updated WHO guidelines for the prevention and management of chronic hepatitis B: Main changes and potential implications for the next major liver society clinical practice guidelines[J]. J Hepatol, 2025, 82( 5): 918- 925. DOI: 10.1016/j.jhep.2024.12.004.
    [3]
    JI D, CHEN Y, BI JF, et al. Entecavir plus Biejia-Ruangan compound reduces the risk of hepatocellular carcinoma in Chinese patients with chronic hepatitis B[J]. J Hepatol, 2022, 77( 6): 1515- 1524. DOI: 10.1016/j.jhep.2022.07.018.
    [4]
    ZHANG Q, CAI DC, HU P, et al. Low-level viremia in nucleoside analog-treated chronic hepatitis B patients[J]. Chin Med J, 2021, 134( 23): 2810- 2817. DOI: 10.1097/CM9.0000000000001793.
    [5]
    HAN JJ, GUO YF, ZHANG XY, et al. Prevalence and associated factors of low-level viremia in chronic hepatitis B patients after long-term therapy with nucleos(t)ide analogs[J]. Turk J Gastroenterol, 2023, 34( 1): 53- 61. DOI: 10.5152/tjg.2023.21978.
    [6]
    TAMAKI N, HUANG DQ, LEE HW, et al. Head-to-head comparison of long-term HCC risk of antivirals-treated versus untreated low-level viremia in HBV-compensated cirrhosis[J]. J Gastroenterol Hepatol, 2025, 40( 6): 1595- 1601. DOI: 10.1111/jgh.16986.
    [7]
    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.
    [8]
    PILKINGTON V, HUGHES SL, PEPPERRELL T, et al. Tenofovir alafenamide vs. tenofovir disoproxil fumarate: An updated meta-analysis of 14 894 patients across 14 trials[J]. AIDS, 2020, 34( 15): 2259- 2268. DOI: 10.1097/QAD.0000000000002699.
    [9]
    Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. 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.
    [10]
    NI ZZ. Health Statistics(4th ed.)[M]. Beijing: People's Medical Publishing House, 2000: 162.

    倪宗瓒. 卫生统计学(第四版)[M]. 北京: 人民卫生出版社, 2000: 162.
    [11]
    XIANG WY, LI SX, LYU RY. Clinical efficacy of sequential tenofovir amibufenamide therapy in chronic hepatitis B patients with low-level viremia after entecavir treatment[J]. China J Mod Med, 2024, 34( 8): 15- 20. DOI: 10.3969/j.issn.1005-8982.2024.08.003.

    向文耀, 李仕雄, 吕日英. 恩替卡韦治疗后慢性乙型肝炎低病毒血症患者序贯联合艾米替诺福韦治疗的效果研究[J]. 中国现代医学杂志, 2024, 34( 8): 15- 20. DOI: 10.3969/j.issn.1005-8982.2024.08.003.
    [12]
    CHON HY, AHN SH, KIM YJ, et al. Efficacy of entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide in treatment-naive hepatitis B patients[J]. Hepatol Int, 2021, 15( 6): 1328- 1336. DOI: 10.1007/s12072-021-10262-y.
    [13]
    MIAO L, JIA CH, CHEN HD, et al. Study on the influencing factors of liver fibrosis regression in patients with chronic hepatitis B achieving virological response after entecavir treatment[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.
    [14]
    CHEN H, FU JJ, LI L, et al. Risk factors of low-level viremia in chronic hepatitis B patients receiving Entecavir monotherapy: A retrospective cohort study[J]. J Gastroenterol Hepatol, 2024, 39( 1): 180- 184. DOI: 10.1111/jgh.16357.
    [15]
    BUTI M, TSAI N, PETERSEN J, et al. Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis B virus infection[J]. Dig Dis Sci, 2015, 60( 5): 1457- 1464. DOI: 10.1007/s10620-014-3486-7.
    [16]
    SU HY, WANG HL, ZHAN J, et al. Efficacy and safety of tenofovir alafenamide fumarate on the prevention of mother-to-child transmission of hepatitis B virus: A systematic review and Meta-analysis[J/CD]. Chin J Liver Dis Electron Version, 2024, 16( 1): 22- 28. DOI: 10.3969/j.issn.1674-7380.2024.01.005.

    苏红艳, 王慧铃, 战军, 等. 富马酸丙酚替诺福韦用于预防乙型肝炎病毒母婴传播有效性和安全性的系统评价[J/CD]. 中国肝脏病杂志(电子版), 2024, 16( 1): 22- 28. DOI: 10.3969/j.issn.1674-7380.2024.01.005.
    [17]
    CHAN HLY, FERRET MAB, AGARWAL K, et al. Maintenance of high levels of viral suppression and improved safety profile of tenofovir alafenamide(TAF) relative to tenfovir disoproxil fumarate(TDF) in chronic hepatitis B patients treated for 5 years in 2 ongoing phase 3 studies[J]. Hepatology, 2020, 72( Suppl1): 490A.
    [18]
    DIAO YT, TANG J, WANG XR, et al. Metabolic syndrome, nonalcoholic fatty liver disease, and chronic hepatitis B: A narrative review[J]. Infect Dis Ther, 2023, 12( 1): 53- 66. DOI: 10.1007/s40121-022-00725-6.
    [19]
    WU Y, LI YW, ZHOU DB. Therapeutic efficacy of switching to tenofovir alafenamide fumarate in entecavir-treated chronic hepatitis B patients with low-level viremia[J]. Chin Hepatol, 2025, 30( 7): 963- 966. DOI: 10.3969/j.issn.1008-1704.2025.07.018.

    吴钰, 李永伟, 周德兵. 恩替卡韦经治慢性乙型肝炎伴低病毒血症患者换用富马酸丙酚替诺福韦治疗的效果[J]. 肝脏, 2025, 30( 7): 963- 966. DOI: 10.3969/j.issn.1008-1704.2025.07.018.
    [20]
    ZHANG RJ. Clinical study on sequential treatment with tenofovir alafenamide for chronic hepatitis B patients treated with Entecavir[D]. Shantou: Shantou University, 2022. DOI: 10.27295/d.cnki.gstou.2022.000595.

    张若锦. 恩替卡韦经治慢性乙型肝炎患者序贯富马酸丙酚替诺福韦治疗的临床研究[D]. 汕头: 汕头大学, 2022. DOI: 10.27295/d.cnki.gstou.2022.000595.
    [21]
    CHENG HL, HU XD, XIA B, et al. Clinical effect of tenofovir alafenamide fumarate on chronic hepatitis B patients with low viral load after entecavir treatment[J]. J Clin Hepatol, 2022, 38( 3): 537- 540. DOI: 10.3969/j.issn.1001-5256.2022.03.009.

    程海林, 胡旭东, 夏冰, 等. 富马酸丙酚替诺福韦对恩替卡韦经治后低病毒载量的慢性乙型肝炎患者的临床疗效[J]. 临床肝胆病杂志, 2022, 38( 3): 537- 540. DOI: 10.3969/j.issn.1001-5256.2022.03.009.
    [22]
    KONG LX, CHEN XF, XU Y, et al. Sequential or combined rescue antiviral therapy by tenofovir amibufenamide in entecavir-treated chronic hepatitis B patients with low-level viremia[J]. J Pract Hepatol, 2025, 28( 3): 334- 337. DOI: 10.3969/j.issn.1672-5069.2025.03.004.

    孔丽霞, 陈旭峰, 许艳, 等. 恩替卡韦经治慢性乙型肝炎低病毒血症患者联合或序贯艾米替诺福韦治疗疗效研究[J]. 实用肝脏病杂志, 2025, 28( 3): 334- 337. DOI: 10.3969/j.issn.1672-5069.2025.03.004.
    [23]
    LI SL, LIU L, CHEN Y, et al. Intestinal barrier function index changes in patients with compensated hepatitis B cirrhosis and high serum viral loads undergoing tenofovir alafenamide fumarate or entecavir therapy[J]. J Pract Hepatol, 2024, 27( 5): 749- 752. DOI: 10.3969/j.issn.1672-5069.2024.05.026.

    李双玲, 刘丽, 陈艺, 等. 富马酸丙酚替诺福韦与恩替卡韦治疗高血清病毒载量的代偿期乙型肝炎肝硬化患者效果比较研究[J]. 实用肝脏病杂志, 2024, 27( 5): 749- 752. DOI: 10.3969/j.issn.1672-5069.2024.05.026.
    [24]
    XIANG WY, ZHU KY, ZHU Q, et al. Comparison of efficacy and safety of Entecavir and Tenofovir profol fumarate in the treatment of chronic hepatitis B with high viral load[J]. Chin Hepatol, 2025, 30( 3): 371- 375. DOI: 10.14000/j.cnki.issn.1008-1704.2025.03.026.

    项伟艳, 朱扣云, 朱琦, 等. 恩替卡韦和富马酸丙酚替诺福韦治疗高病毒载量慢性乙型肝炎的疗效和安全性比较[J]. 肝脏, 2025, 30( 3): 371- 375. DOI: 10.14000/j.cnki.issn.1008-1704.2025.03.026.
    [25]
    MA SP, YU YQ, WU XP, et al. Changes in renal function in chronic hepatitis B patients treated initially with entecavir versus tenofovir alafenamide fumarate and related influencing factors[J]. J Clin Hepatol, 2025, 41( 1): 44- 51. DOI: 10.12449/JCH250107.

    马仕鹏, 余燕青, 邬小萍, 等. 恩替卡韦与富马酸丙酚替诺福韦初治慢性乙型肝炎患者的肾功能变化比较及影响因素分析[J]. 临床肝胆病杂志, 2025, 41( 1): 44- 51. DOI: 10.12449/JCH250107.
    [26]
    EKE AC, BRUMMEL SS, ALIYU MH, et al. Lipid and glucose profiles in pregnant women with HIV on tenofovir-based antiretroviral therapy[J]. Clin Infect Dis, 2025, 80( 3): 594- 601. DOI: 10.1093/cid/ciae441.
    [27]
    KAUPPINEN KJ, AHO I, SUTINEN J. Switching from tenofovir alafenamide to tenofovir disoproxil fumarate improves lipid profile and protects from weight gain[J]. AIDS, 2022, 36( 10): 1337- 1344. DOI: 10.1097/QAD.0000000000003245.
    [28]
    ORKIN C, ERON JJ, ROCKSTROH J, et al. Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients[J]. AIDS, 2020, 34( 5): 707- 718. DOI: 10.1097/QAD.0000000000002463.
    [29]
    DENG HC, CUI NN, LI B, et al. The correlation between healthy lifestyle scores and the risk of dyslipidemia, hypertension and diabetes among elderly population[J]. Acta Med Univ Sci Technol Huazhong, 2023, 52( 2): 245- 251. DOI: 10.3870/j.issn.1672-0741.2023.02.018.

    邓海潮, 崔宁宁, 李冰, 等. 老年人群健康生活方式评分与血脂异常、高血压和糖尿病风险的相关性研究[J]. 华中科技大学学报(医学版), 2023, 52( 2): 245- 251. DOI: 10.3870/j.issn.1672-0741.2023.02.018.
    [30]
    PENG WT, GU HM, JIANG C, et al. Comparison of tenofovir alafenamide and entecavir for hepatitis B virus-related acute-on-chronic liver failure[J]. J Cent South Univ(Med Sci), 2022, 47( 2): 194- 201. DOI: 10.11817/j.issn.1672-7347.2022.210578.

    彭文婷, 顾慧敏, 蒋川, 等. 富马酸丙酚替诺福韦与恩替卡韦治疗乙型肝炎病毒相关慢加急性肝衰竭的效果对比[J]. 中南大学学报(医学版), 2022, 47( 2): 194- 201. DOI: 10.11817/j.issn.1672-7347.2022.210578.
    [31]
    HUANG YJ, LEE SW, TUNG CF, et al. HBV relapse after discontiniuation of tenofovir alafenamide or entecavir in non-cirrhotic hepatitis B e antigen-negative patients[J]. Dig Dis, 2025, 43( 3): 336- 344. DOI: 10.1159/000544870.
    [32]
    ARNOUK S, WHITSETT M, PAPADOPOULOS J, et al. Successful treatment of tenofovir alafenamide-induced lactic acidosis: A case report[J]. J Pharm Pract, 2023, 36( 5): 1260- 1263. DOI: 10.1177/08971900221105042.
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