艾米替诺福韦与丙酚替诺福韦挽救治疗低病毒血症的慢性乙型肝炎患者临床研究*

doi:10.3969/j.issn.1672-5069.2025.05.007

摘要/Abstract

摘要： 目的观察应用艾米替诺福韦(TMF)和丙酚替诺福韦(TAF)挽救治疗经治的出现低病毒血症(LLV)的慢性乙型肝炎(CHB)患者的临床疗效。方法 2022年1月～2024年1月我院收治的既往经恩替卡韦(ETV)治疗至少12个月应答不完全的CHB患者68例,采用随机数字表法将患者分为观察组和对照组,每组34例,停止ETV治疗后分别转换为TMF治疗或TAF治疗,两组均持续治疗观察48w。使用超声肝脏瞬时弹性成像设备行肝硬度检测(LSM),采用电化学发光法检测血清HBV标志物,采用电化学发光法检测血清透明质酸(HA)、层黏连蛋白(LN)、Ⅳ型胶原(Ⅳ-C)和Ⅲ型前胶原(PCⅢ),采用荧光探针PCR法检测血清HBV DNA载量,使用贝克曼BX800全自动生化分析仪检测血生化指标。结果在治疗48 w末,观察组LSM及血清HA、LN、Ⅳ-C和PCⅢ水平分别为(6.8±1.2)KPa、(171.2±25.9)ng/mL、(147.5±42.3)ng/mL、(174.3±46.3)ng/mL和(56.8±12.4)ng/mL,与对照组【分别(6.9±1.2)KPa、(175.2±34.6)ng/mL、(148.2±46.3)ng/mL、(175.4±42.1)ng/mL和(55.5±19.5)ng/mL】比,无显著性差异(P>0.05);观察组血清总胆红素、丙氨酸氨基转移和天冬氨酸氨基转移酶水平分别为(16.4±1.4)μmol/L、(40.3±4.8)U/L和(32.4±5.1)U/L,与对照组【分别为(17.3±1.2)μmol/L、(41.8±4.5)U/L和(36.9±4.9)U/L】比,差异无显著性统计学意义(P>0.05);两组血清HBV DNA载量和ALT水平均恢复正常,两组生化和病毒学应答率比较,无显著性差异(P>0.05)。结论对于ETV经治的出现LLV的CHB患者,给予TAF或TMF挽救治疗均可获得较好的临床疗效,都获得了完全病毒学应答,其长期疗效还有待于继续观察。

关键词: 乙型肝炎, 恩替卡韦, 低病毒血症, 艾米替诺福韦, 丙酚替诺福韦, 挽救治疗

Abstract: Objective The aim of this study was to investigate clinical efficacy of tenofovir amibufenamide (TMF) and tenofovir alafenamide fumarate (TAF) in rescue treatment of entecavir (ETV)-treated patients with chronic hepatitis B(CHB) and low-level viremia (LLV). Methods 68 patients with CHB were enrolled in our hospital between January 2022 and January 2024, the enrolled patients were all ETV-treated for at least 12 months, showing poor virological response with LLV and were randomly assigned to receive TMF or TAF for 48 weeks. Liver stiffness measurement (LSM) was evaluated by ultrasonic liver transient elastography, serum HBV markers, biochemical parameters and HBV DNA loads were routinely detected. Serum laminin(LN),collagen type Ⅳ(Ⅳ-C), precollagen-Ⅲ (PC-Ⅲ)and hyaluronic acid(HA)levels were assayed by ELISA. Results By end of 48 week treatment, LSM as well as serum HA, LN, Ⅳ-C and PCⅢ levels in TMF-treated patients were (6.8±1.2)KPa, (171.2±25.9)ng/mL, (147.5±42.3)ng/mL, (174.3±46.3)ng/mL and (56.8±12.4)ng/mL, all not significantly different as compared to [(6.9±1.2)KPa, (175.2±34.6)ng/mL, (148.2±46.3)ng/mL, (175.4±42.1)ng/mL and (55.5±19.5)ng/mL, respectively] in TAF-treated patients (P>0.05); serum bilirubin, ALT and AST levels in TMF-treated patients were (16.4±1.4)μmol/L, (40.3±4.8)U/L and (32.4±5.1)U/L, all not significantly different as compared to [(17.3±1.2)μmol/L, (41.8±4.5)U/L and (36.9±4.9)U/L, respectively] in TAF-treated patients (P>0.05); virological and biochemical response rates in the two groups were not significantly different as serum HBV DNA transferred to negative and serum ALT level returned to normal(P>0.05) in all patients. Conclusion As for patients with CHB and poor response to ETV treatment, rescue antiviral therapy with TMF or TAF is both satisfactory, with complete virological response, and the long-term efficacy should be followed-up in the future.

Key words: Hepatitis B, Entecavir, Low-level viremia, Tenofovir amibufenamide, Tenofovir alafenamide fumarate, Rescue therapy

袁铃, 姜霞, 孙美杰, 岳冬黎, 张晓玲. 艾米替诺福韦与丙酚替诺福韦挽救治疗低病毒血症的慢性乙型肝炎患者临床研究^*[J]. 实用肝脏病杂志, 2025, 28(5): 667-670.

Yuan Ling, Jiang Xia, Sun Meijie. Clinical efficacy of tenofovir amibufenamide and tenofovir alafenamide fumarate in rescue treatment of ETV-treated patients with chronic hepatitis B and low-level viremia[J]. Journal of Practical Hepatology, 2025, 28(5): 667-670.

参考文献

[1] Shanshan W, Xinfang D, Shuihong Y,et al. Pathological changes of liver one year later in CHB patients with negative HBV DNA. Infect Agent Cancer, 2019,10(14):48.
[2] World Health Organization. Hepatitis B [Internet] Geneva: World Health Organization. 2019. [cited 2024 Dec 6] . Available from:https://www.who.int/news-room/fact-sheets/detail/hepatitis-b.
[3] Liu Y, Liu H, Hu Z,et al. Hepatitis B virus virions produced under nucleos(t)ide analogue treatment are mainly not infectious because of irreversible DNA chain termination. Hepatology, 2020, 71(2):463-476.
[4] Su CW, Wu CY, Lin JT,et al. Nucleos(t)ide analogue continuous therapy associated with reduced adverse outcomes of chronic hepatitis B. J Chin Med Assoc, 2020 ,83(2):125-133.
[5] Yamashige D, Hosaka T, Suzuki F, et al. Effectiveness of tenofovir alafenamide for chronic hepatitis B patients with a poor response to the previously used nucleos(t)ide analogs. J Gastroenterol, 2021, 56(11):1008-1021.
[6] Woo HY, Park JY, Bae SH,et al. Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response. Clin Mol Hepatol, 2020, 26(3):352-363.
[7] Buti M, Roade L, Riveiro-Barciela M,et al. Optimal management of chronic hepatitis B patients receiving nucleos(t)ide analogues. Liver In, 2020, 40 (Suppl 1):15-21.
[8] Charlton MR, Alam A, Shukla A,et al. An expert review on the use of tenofovir alafenamide for the treatment of chronic hepatitis B virus infection in Asia. J Gastroenterol, 2020, 55(9):811-823.
[9] 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(2015年版). 实用肝脏病杂志,2016,19(3):389-400.
[10] Said M, Eletreby R, Omar H,et al. Fibro-indices versus liver stiffness for prediction of significant fibrosis in hepatitis B virus-infected Egyptian patients; a single-center experience. Expert Rev Gastroenterol Hepatol, 2020 ,14(3):221-227.
[11] Bâldea V, Sporea I, Tudor A,et al. Virtual touch quantification using acoustic radiation force impulse imaging technology versus transient elastography for the noninvasive assessment of liver fibrosis in patients with chronic hepatitis B or C using liver biopsy as the gold standard. J Gastrointestin Liver Dis, 2020, 29(2):181-190.
[12] Peng CW, Jeng WJ. Understanding more about hepatitis flare in chronic hepatitis B patients. Clin Gastroenterol Hepatol, 2020, 18(1):266-267.
[13] Cao G, Jing W, Liu J,et al. Countdown on hepatitis B elimination by 2030: the global burden of liver disease related to hepatitis B and association with socioeconomic status. Hepatol Int, 2022, 16(6):1282-1296.
[14] Polaris Observatory Collaborators. Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study. Lancet Gastroenterol Hepatol, 2023 ,8(10):879-907.
[15] Wang Y, Li XY, Wu LL,et al. Dynamic prediction of liver cirrhosis risk in chronic hepatitis B patients using longitudinal clinical data. Eur J Gastroenterol Hepatol, 2020, 32(1):120-126.
[16] Flemming JA, Terrault NA. Tenofovir vs entecavir for hepatocellular carcinoma prevention in patients with chronic hepatitis B: One of these things is not like the other. JAMA Oncol, 2019, 5(1):17-18.
[17] Li Q, Huang C, Xu W,et al. Accuracy of FibroScan in analysis of liver fibrosis in patients with concomitant chronic hepatitis B and nonalcoholic fatty liver disease. Medicine (Baltimore), 2020, 99(23):e20616.
[18] He T, Li J, Ouyang Y,et al. FibroScan detection of fatty liver/liver fibrosis in 2266 cases of chronic hepatitis B. J Clin Transl Hepatol, 2020, 8(2):113-119.
[19] Hagiwara S, Nishida N, Ida H,et al. Switching from entecavir to tenofovir alafenamide versus maintaining entecavir for chronic hepatitis B. J Med Virol,2019, 91(10):1804-1810.
[20] Uchida Y, Nakao M, Yamada S,et al. Superiority of tenofovir alafenamide fumarate over entecavir for serum HBsAg level reduction in patients with chronic HBV infection: A 144-week outcome study after switching of the nucleos(t)ide analog. PLoS One, 2022, 17(2):e0262764.
[21] Li L, Zhou J, Li Y, et al. Effectiveness and safety of tenofovir amibufenamide and its comparison with tenofovir alafenamide in patients with chronic hepatitis B: results from a retrospective real-world study. Front Pharmacol, 2023, 14:1165990.
[22] Peng WT, Jiang C, Yang FL,et al. Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: A real-world study. World J Gastroenterol, 2023, 29(44):5907-5918.
[23] 金晶晶,金丹丹.健脾清热方辅助治疗对慢性乙型肝炎患者肝功能、免疫功能和血清HBsAg水平的影响.中华医院感染学杂志,2024,34(14):2108-2112.
[24] 张全乐,赵丹,李杰,等.富马酸替诺福韦与恩替卡韦挽救治疗拉米夫定耐药的HBeAg阴性慢性乙型肝炎患者疗效分析.实用肝脏病杂志,2024,27(4):515-518.
[25] Ogawa E, Nomura H, Nakamuta M, et al. Tenofovir alafenamide after switching from entecavir or nucleostide combination therapy for patients with chronic hepatitis B. Liver Int, 2020, 40(7):1578-1589.
[26] Li ZB, Li L, Niu XX, et al. Switching from entecavir to tenofovir alafenamide for chronic hepatitis B patients with low-level viraemia. Liver Int, 2021, 41(6):1254-1264.
[27] Yuan BH, Li RH, Huo RR,et al. Lower risk of hepatocellular carcinoma with tenofovir than entecavir treatment in subsets of chronic hepatitis B patients: an updated meta-analysis. J Gastroenterol Hepatol, 2022, 37(5):782-794.
[28] 何振文,徐刚,孟华,等. 艾米替诺福韦再治疗低病毒血症的慢性乙型肝炎患者临床疗效研究. 实用肝脏病杂志,2024,27(6):828-831.

艾米替诺福韦与丙酚替诺福韦挽救治疗低病毒血症的慢性乙型肝炎患者临床研究^*

Clinical efficacy of tenofovir amibufenamide and tenofovir alafenamide fumarate in rescue treatment of ETV-treated patients with chronic hepatitis B and low-level viremia

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