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*

doi:10.3969/j.issn.1672-5069.2024.04.006

实用肝脏病杂志 ›› 2024, Vol. 27 ›› Issue (4): 515-518.doi: 10.3969/j.issn.1672-5069.2024.04.006

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^*

张全乐, 赵丹, 李杰, 刘三香, 刘刚, 李亚

061000 河北省沧州市沧州中西医结合医院消化科(张全乐,李杰,刘三香,刘刚,李亚);南京中医药大学附属医院消化科(赵丹)

收稿日期:2024-03-25 出版日期:2024-07-10 发布日期:2024-07-10
作者简介:张全乐,男,43岁,医学硕士,副主任医师。E-mail:zhangquanle@163.com ·
基金资助:
^*河北省沧州市重点研发计划指导项目(编号:204106049)

Rescue antiviral therapy of patients withlamivudine-resistant chronic hepatitis B: tenofovir or entecavir superior?

Zhang Quanle, Zhao Dan, Li Jie, et al

Department of Gastroenterology, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 061000, Hebei Province, China

Received:2024-03-25 Online:2024-07-10 Published:2024-07-10

摘要/Abstract

摘要： 目的探讨应用富马酸替诺福韦(TDF)与恩替卡韦(ETV)挽救治疗拉米夫定耐药的血清HBeAg阴性的慢性乙型肝炎(CHB)患者的临床疗效,并分析影响临床疗效的因素。方法 2017年1月～2021年12月我院收治的拉米夫定治疗耐药的血清HBeAg阴性的CHB患者50例,被随机分为TDF治疗组25例和ETV治疗组25例,前者常规剂量应用,后者加倍应用。两组均治疗48周,监测疗效。应用二分类变量的Logistic回归分析影响病毒学应答的因素。结果在治疗4周、12周、24周、36周和48周时,TDF治疗组血清HBV DNA累积转阴率分别为32%、60%、72%、80%和92%,显著高于ETV治疗组(分别为4%、24%、32%、40%和44%,均P<0.05);TDF治疗组血清ALT复常率分别为56%、68%、80%、84%和96%,与显著高于ETV治疗组(分别为16%、32%、52%、56%和72%,均P<0.05);在治疗48周时,TDF治疗组血清肌酐水平显著高于治疗前(85.4±13.9μmol/L对76.2±17.5μmol/L,P=0.0001),而ETV治疗组治疗前后血清肌酐水平无显著变化(76.6±12.9μmol/L对77.3±11.2μmol/L,P=0.769);Logistic回归分析显示,应用TDF治疗和血清HBV DNA载量为影响血清HBV DNA转阴的独立预测因素。结论 TDF挽救治疗拉米夫定耐药的CHB患者可能获得更好的疗效,但需要密切监测肾功能的变化。

关键词: 慢性乙型肝炎, 替诺福韦, 恩替卡韦, 拉米夫定, 耐药, 挽救治疗

Abstract: Objective This study was conducted to investigate clinical efficacy of tenofovir disoproxil fumarate (TDF) and entecavir (ETV) in rescue therapy of patients with lamivudine-resistant HBeAg-negative chronic hepatitis B (CHB). Methods Fifty patients with lamivudine-resistant HBeAg-negative CHB were enrolled in our hospital between January 2017 and December 2021, and we randomly assigned them to receive TDF (n=25) or ETV for rescue antiviral therapy for 48 weeks. Multivariate Logistic regression analysis was applied to predict impacting factors for virological response. Results by 4, 12, 24, 36 and 48 weeks of antiviral treatment, serum HBV DNA loss in TDF-treated patients were 32%, 60%, 72%, 80% and 92%, all much higher than 4%, 24%, 32%, 40% and 44% (all P<0.05) in ETV-treated patients; serum ALT normalization rates in TDF-treated patients were 56%, 68%, 80%, 84% and 96%, all much higher than 16%, 32%, 52%, 56% and 72% (P<0.05) in ETV-treated patients; by end of 48 week treatment, serum creatinine level in TDF-treated patients increased greatly as compared to that at presentation (85.4±13.9μmol/L vs. 76.2±17.5μmol/L, P=0.0001), while it didn’t change obviously in ETV-treated patients (76.6±12.9μmol/L vs. 77.3±11.2μmol/L, P=0.769); multivariate Logistic regression analysis showed that administration of TDF and serum HBV DNA loads were independent factors impacting virologcal response to rescue therapy. Conclusion Based on our findings, we recommend TDF rescue antiviral therapy for CHB patients with lamivudine-resistant, and surveillance of renal functions might be important during the antiviral procedure.

Key words: Hepatitis B, Lamivudine-resistance, Tenofovir, Entecavir, Rescue therapy

张全乐, 赵丹, 李杰, 刘三香, 刘刚, 李亚. 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^*[J]. 实用肝脏病杂志, 2024, 27(4): 515-518.

Zhang Quanle, Zhao Dan, Li Jie, et al. Rescue antiviral therapy of patients withlamivudine-resistant chronic hepatitis B: tenofovir or entecavir superior?[J]. Journal of Practical Hepatology, 2024, 27(4): 515-518.

参考文献

[1] 中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南(2022年版).实用肝脏病杂志,2023,26(3)S18-39.
[2] 肝脏硬度评估小组.瞬时弹性成像技术诊断肝纤维化专家意见.中华肝脏病杂志,2013,21(6):420-425.
[3] Nguyen MH, Wong G, Gane E, et al.Hepatitis B virus: advances in prevention, diagnosis, and therapy.Clin Microbiol Rev,2020,33(2):e00046-19.
[4] Alexopoulou A, Karayiannis P. HBeAg negative variants and their role in the natural history of chronic hepatitis B virus infection. World J Gastroenterol,2014,20(24): 7644-7652.
[5] Guvenir M, Arikan A.Hepatitis B virus: from diagnosis to treatment.Pol J Microbiol,2020,69(4):391-399.
[6] Lee J, Tsai KN, Ou JJ.Mechanisms of hepatitis B virus-induced hepatocarcinogenesis.Recent Results Cancer Res,2021,217:47-70.
[7] Li H, Yan L, Shi Y, et al. Hepatitis B virus infection: overview.Adv Exp Med Biol,2020,1179:1-16.
[8] Jeng WJ, Papatheodoridis GV, Lok ASF.Hepatitis B. Lancet,2023,401(10381):1039-1052.
[9] Lee HW, Lee JS, Ahn SH.Hepatitis B virus cure: targets and future therapies. Int J Mol Sci,2020,22(1):213.
[10] Fanning GC, Zoulim F, Hou J, et al.Therapeutic strategies for hepatitis B virus infection:towards a cure.Nat Rev Drug Discov,2019,18(11):827-844.
[11] Maepa MB, Bloom K, Ely A, et al.Hepatitis B virus: promising drug targets and therapeutic implications.Expert Opin Ther Targets,2021,25(6):451-466.
[12] Oh JM, Kyun J, Cho SW. Long-term lamivudine therapy for chronic hepatitis B in patients with and without cirrhosis. Pharmacotherapy,2002,22:1226-1234.
[13] Sherman M, Yurdaydin C, Sollano J, et al. Entecavir for treatment of lamivudine-refractory,HBeAg-positive chronic hepatitis B. Gastroenterology,2006,130(7):2039-2049.
[14] Kim HJ, Park JH, Park DI, et al. Rescue therapy for lamivudine-resistant chronic hepatitis B: comparison between entecavir 1.0 mg monotherapy, adefovir monotherapy and adefovir add-on lamivudine combination therapy. J Gastroenterol Hepatol,2010,25(8):1374-1380.
[15] Yang DH, Xie YJ, Zhao NF, et al.Tenofovir disoproxil fumarate is superior to lamivudine plus adefovir in lamivudine-resistant chronic hepatitis B patients.World J Gastroenterol, 2015,21(9):2746-2753.
[16] Meng Z, Chen Y, Lu M.Advances in targeting the Innate and adaptive immune systems to cure chronic hepatitis B virus infection.Front Immunol, 2020,10:3127.
[17] Liaw YF, Chien RN. Finite nucleos(t)ide analogue therapy in hepatitis B e antigen-negative chronic hepatitis B: From an “option” to an “active recommendation”. Kaohsiung J Med Sci, 2022,38:295-301.
[18] Marcellin P, Gane EJ, Flisiak R, et al. Long term treatment with tenofovir disoproxil fumarate for chronic hepatitis B infection is safe and well tolerated and associated with durable virologic response with no detectable resistance: 8 year results from two phase 3 trials. Hepatology, 2014,60:313A-317A.
[19] Van Bömmel F, Berg T.Risks and benefits of discontinuation of nucleos(t)ide analogue treatment: A treatment concept for patients with HBeAg-negative chronic hepatitis B. Hepatol Commun,2021,5(10):1632-1648.
[20] Ezinga M, Wetzels JF, Bosch ME, et al.Long-term treatment with tenofovir: prevalence of kidney tubulardysfunction andits association with tenofovir plasma concentration. Antivir Ther,2014,19(8):765-771.

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^*

Rescue antiviral therapy of patients withlamivudine-resistant chronic hepatitis B: tenofovir or entecavir superior?

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