替诺福韦酯与恩替卡韦治疗慢性乙型肝炎患者疗效和血清成纤维细胞生长因子-23水平变化

doi:10.3969/j.issn.1672-5069.2021.02.013

摘要/Abstract

摘要： 目的探讨替诺福韦酯与恩替卡韦治疗慢性乙型肝炎(CHB)患者的疗效和血清成纤维细胞生长因子-23(FGF-23)水平的变化。方法 2018年1月～2019年1月我院就诊的150例CHB患者被随机分为两组,每组75例,分别给予恩替卡韦或替诺福韦治疗,观察48 w。采用ELISA法测定血清β2-微球蛋白(β2-MG)、FGF-23和胱抑素-C(Cys-C水平),使用ABI7300荧光定量PCR分析仪检测血清HBV DNA水平。结果在治疗观察结束时,替诺福韦治疗组血清HBV DNA转阴率为100.0 %,显著高于恩替卡韦治疗组的93.3 %(P<0.05),而两组血清HBeAg转阴率和血清谷丙转氨酶(ALT)复常率比较,无统计学差异(分别为10.1%对8.0%和96.0%对93.3%,P>0.05);替诺福韦治疗组血清HBV DNA水平为(0.9 ± 0.5)Ig IU/mL,与恩替卡韦治疗组的(1.3 ± 0.6)Ig IU/mL比,无统计学差异(P>0.05),两组血清ALT和AST水平比较,也无统计学差异(P>0.05);替诺福韦治疗组血清β2-MG水平为(1.6 ± 0.5)mg/L,显著高于恩替卡韦治疗组【(1.4 ± 0.5)mg/L,P<0.05】,血清FGF-23水平为(382.2 ± 61.3)pg/mL,显著高于恩替卡韦治疗组【(363.2 ± 53.3)pg/mL,P<0.05】,血清Cys-C水平为(3.0 ± 0.8)mg/L,显著高于恩替卡韦治疗组【(2.8 ± 0.8)mg/L,P<0.05】。结论恩替卡韦和替诺福韦酯治疗CHB患者均能获得良好的近期疗效,但替诺福韦治疗能升高血清β2-MG、FGF-23和Cys-C水平,其意义和对远期疗效的影响还需要进一步评估。

关键词: 慢性乙型肝炎, 替诺福韦酯, 恩替卡韦, 成纤维细胞生长因子-23, 治疗

Abstract: Objective The aim of this study was to investigate the short-term efficacy of tenofovir dipivoxil and entecavir in treating patients with chronic hepatitis B (CHB) and serum fibroblast growth factor-23 (FGF-23) level changes.Methods 150 patients with CHB were recruited in our hospital between January 2018 and January 2019, and were divided into two groups, with 75 in each, receiving entecavir or tenofovir for 48 weeks. Serum cytokine levels in the two groups before and after 48 weeks of treatment were detected by ELISA.Results At the end of 48-week treatment, serum HBV DNA loss in the tenofovir-treated group was 100.0 %, which was significantly higher than 93.3% (P<0.05) in the entecavir-treated group, However, there were no statistical significant differences as respect to serum HBeAg negative or serum alanine aminotransferase normalization between the two groups (10.1% vs. 8.0% and 96.0% vs. 93.3%, respectively, P>0.05); serum HBV DNA level in tenofovir-treated group was(0.9 ± 0.5)Ig IU/mL, not significantly different compared to(1.3 ± 0.6)Ig IU/mL in entecavir-treated group (P>0.05), and there were no significant differences with respect to serum ALT and AST levels between the two groups (P>0.05); serum β2-microglobulin, FGF-23 and cystatin-C levels in tenofovir-treated group were(1.6 ± 0.5)mg/L, (382.2 ± 61.3)pg/mL and (3.0 ± 0.8)mg/L, all significantly higher than 【(1.4 ± 0.5)mg/L,(363.2 ± 53.3)pg/mL and(2.8 ± 0.8)mg/L, respectively, P<0.05】 in the entecavir-treated group.Conclusion The oral administration of entecavir or tenofovir disoproxil in the treatment of patients with CHB could obtain short-term response as serum HBV DNA loss and serum ALT normalization, while the implication of elevated serum β2-MG, FGF-23 and Cys-C levels needs further investigation.

Key words: Hepatitis B, Tenofovir disoproxil, Entecavir, Fibroblast growth factor-23, Therapy

贺宇峰, 钟晓妮, 黄建溶, 赖思奇. 替诺福韦酯与恩替卡韦治疗慢性乙型肝炎患者疗效和血清成纤维细胞生长因子-23水平变化[J]. 实用肝脏病杂志, 2021, 24(2): 200-203.

He Yufeng, Zhong Xiaoni, Huang Jianrong, et al. Short-term efficacy of tenofovir dipivoxil and entecavir in the treatment of patients with chronic hepatitis B[J]. Journal of Practical Hepatology, 2021, 24(2): 200-203.

参考文献

[1] Gish RG, Given BD, Lai CL, et al. Chronic hepatitis B: virology, natural history, current management and a glimpse at future opportunities. Antiviral Res, 2015, 121(1):47-58.
[2] Lok AS, McMahon BJ, Brown RS, et al. Antiviral therapy for chronic hepatitis B viral infection in adults: a systematic review and meta-analysis. Hepatology, 2016, 63(1):284-306.
[3] Adjei CA, Stutterheim SE, Naab F, et al. Barriers to chronic hepatitis B treatment and care in Ghana: a qualitative study with people with hepatitis B and healthcare providers. PLoS One, 2019, 14(12):225-228.
[4] Chan HL, Fung S, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol, 2016, 1(3):185-195.
[5] Choi J, Kim HJ, Lee J, et al. Risk of hepatocellular carcinoma in patients treated with entecavir vs tenofovir for chronic hepatitis B: a Korean nationwide cohort study. JAMA Oncol, 2019, 5(1):30-36.
[6] 王贵强, 王福生, 成军, 等. 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.
[7] Kostyusheva A, Kostyushev D, Brezgin S, et al. Clinical implications of hepatitis B virus RNA and covalently closed circular DNA in monitoring patients with chronic hepatitis B today with a gaze into the future: the field is unprepared for a sterilizing cure. Genes, 2018, 9(10):483.
[8] Ahn SH, Marcellin P, Ma X, et al. Hepatitis B surface antigen loss with tenofovir disoproxil fumarate plus peginterferon alfa-2a: week 120 analysis. Dig Dis Sci, 2018, 63(12):3487-3497.
[9] Kim YM, Shin HP, Lee JI, et al. Real-world single-center experience with entecavir and tenofovir disoproxil fumarate in treatment-naïve and experienced patients with chronic hepatitis B. Saudi J Gastroen, 2018, 24(6):326-335.
[10] Iida-Ueno A, Enomoto M, Kozuka R, et al. Switching to tenofovir disoproxil fumarate vs continuing treatment in patients with chronic hepatitis B who maintain long-term virological response to entecavir therapy: a randomized trial. J Med Virol, 2019, 91(7):1295-1300.
[11] Buti M, Gane E, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatiti B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroen Hepatol, 2016, 1(3):196-206.
[12] 李传杰, 徐静, 王亮亮, 等. 恩替卡韦治疗慢性乙型肝炎患者血清HBsAg变化与病毒学应答的相关性研究. 实用肝脏病杂志, 2019, 22(6):928-929.
[13] Huang YS, Sun HY, Chang SY, et al. Long-term virological and serologic responses of chronic hepatitis B virus infection to tenofovir disoproxil fumarate-containing regimens in patients with HIV and hepatitis B coinfection. Hepatol Int, 2019, 13(4):431-439.
[14] Marcellin P, Ahn SH, Ma X, et al. Combination of tenofovir disoproxil fumarate and peginterferon α-2a increases loss of hepatitis B surface antigen in patients with chronic hepatitis B. Gastroen, 2016, 150(1):134-144.
[15] Childs-Kean LM, Egelund EF, Jourjy J, et al. Tenofovir alafenamide for the treatment of chronic hepatitis B monoinfection. Pharmacology, 2018, 38(10):1051-1057.
[16] Liang RY, Xu JH, Si CW, et al. A randomized, double-blind, double-dummy, controlled, multicenter study of Qingzhong (tenofovir disoproxil fumarate) versus viread for the treatment of chronic hepatitis B: first-stage results at week 48. Medicine, 2019, 98(33):167-168.
[17] Papatheodoridis GV, Rigopoulou EI, Papatheodoridi M, et al. Daring-B: discontinuation of effective entecavir or tenofovir disoproxil fumarate long-term therapy before HBsAg loss in non-cirrhotic HBeAg-negative chronic hepatitis B. Antivir Ther, 2018, 23(8):677-685.
[18] 杨蕊西, 刘茗心, 陈泠忻, 等. 替诺福韦酯挽救治疗HBV DNA聚合酶区204位点突变的经治慢性乙型肝炎患者疗效和安全性分析. 实用肝脏病杂志, 2019, 22(3):349-352.
[19] Hsu YC, Wei MT, Nguyen MH, et al. Tenofovir alafenamide as compared to tenofovir disoproxil fumarate in the management of chronic hepatitis B with recent trends in patient demographics. Expert Rev, 2017, 11(11):999-1008.
[20] 卢婷, 李成忠. 替诺福韦酯挽救治疗对核苷(酸)类药物耐药的慢性乙型肝炎研究进展.实用肝脏病杂志, 2016, 19(3):369-372.
[21] Papatheodoridis G, Dalekos G, Sypsa V, et al. Page-B predicts the risk of developing hepatocellular carcinoma in Caucasians with chronic hepatitis B on 5-year antiviral therapy. J Hepatol, 2016, 64(4):800-806.
[22] Song JE, Lee CH, Kim BS, et al. Efficacy of long-term tenofovir disoproxil fumarate therapy in chronic hepatitis B patients with partial virologic response in real practice. Korean J Intern Med, 2019, 34(4):802-810.
[24] Tsai HJ, Chuang YW, Lee SW, et al. Using the chronic kidney disease guidelines to evaluate the renal safety of tenofovir disoproxil fumarate in hepatitis B patients. Aliment Pharmacol Ther, 2018, 47(12):1673-1681.
[25] Cressey TR, Harrison L, Achalapong J, et al. Tenofovir exposure during pregnancy and postpartum in women receiving tenofovir disoproxil fumarate for the prevention of mother-to-child transmission of hepatitis B virus. Anti Agen Chem, 2018, 62(12):1686-1688.