聚乙二醇干扰素α-2b联合恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者疗效研究*

doi:10.3969/j.issn.1672-5069.2024.05.008

摘要/Abstract

摘要： 目的观察比较聚乙二醇干扰素α-2b(Peg-IFN-α)联合恩替卡韦治疗血清HBeAg阳性的慢性乙型肝炎(CHB)患者的疗效。方法 2019年1月～2022年1月我院收治的279例血清HBeAg阳性的CHB患者,被分为3组,每组93例,分别给予恩替卡韦口服治疗、Peg-IFN-α皮下注射治疗或恩替卡韦联合Peg-IFN-α治疗,均持续治疗48 w,评估疗效。常规检测血清生化学、血清学和病毒学指标。结果在治疗48 w末,联合组HBeAg转阴率和HBeAg血清转换率分别为32.3%和21.5%,Peg-IFN-α治疗组分别为22.6%和15.1%,而恩替卡韦治疗组则无血清HBeAg转阴或HBeAg血清转换者,联合组尚有一些零星的病例发生HBsAg转阴(3.2%)或HBsAg血清转换(2.2%);联合组血清HBsAg和HBeAg水平分别为(1.9±0.3)lg s/co和(0.5±0.1)lg s/co,Peg-IFN-α治疗组分别为(2.2±0.2)lg s/co和(0.6±0.1)lg s/co,均显著低于恩替卡韦治疗组【分别为(3.6±0.2)lg s/co和(1.3±0.2)lg s/co,P＜0.05】,而联合组和恩替卡韦治疗组血清HBV DNA载量均显著低于Peg-IFN-α治疗组(P＜0.05);联合组血清ALT和AST水平分别为(30.9±4.5)U/L和(28.4±5.3)U/L,恩替卡韦治疗组分别为(31.5±3.6)U/L和(32.3±4.7)U/L,均显著低于Peg-IFN-α治疗组【分别为(48.1±4.2)U/L和(42.7±5.0)U/L,P＜0.05】。结论联合应用恩替卡韦和Peg-IFN-α治疗血清HBeAg阳性的CHB患者可能获得更好的血清学转换率,在优势人群可能获得功能性治愈,值得深入研究。

关键词: 慢性乙型肝炎, 聚乙二醇干扰素α-2b, 恩替卡韦, 治疗, 功能治愈

Abstract: Objective The aim of this study was to investigate antiviral efficacy of peginterferon alpha (Peg-IFN-α) and entecavir (ETV) combination in treatment of patients with serum HBeAg-positive chronic hepatitis B (CHB). Methods A total of 279 patients with serum HBeAg-positive CHB were enrolled in this study between January 2019 and January 2022, and were randomly divided into three groups, with 93 cases in each group. Oral entecavir, subcutaneous injection of Peg-IFN-α, or combination of entecavir and Peg-IFN-α were given, and antiviral regimen lasted for 48 weeks. Serum biochemical, serological and virological responses were routinely assessed. Results By end of 48 week treatment, serum HBeAg negative rate and seroconversion rate in combination group were32.3% and 21.5%, in Peg-IFN-α group were 22.6% and 15.1%, while in entecavir group, no serum HBeAg negative and no serum HBeAg conversion; also in combination group, 3.2% of patients had serum HBsAg negative and 2.2% of them had serum HBsAg seroconversion; serum HBsAg and HBeAg levels in combination group were (1.9±0.3)lg s/co and (0.5±0.1)lg s/co, in Peg-IFN-α group were (2.2±0.2)lg s/co and (0.6±0.1)lg s/co, both significantly lower than [(3.6±0.2)lg s/co and (1.3±0.2)lg s/co, P＜0.05] in entecavir group, while serum HBV DNA loads in combination and entecavir groups were much lower than in Peg-IFN-α group (P＜0.05); serum ALT and AST levels in combination group were (30.9±4.5)U/L and (28.4±5.3)U/L, in entecavir group were (31.5±3.6)U/L and (32.3±4.7)U/L, both significantly lower than [(48.1±4.2)U/L and (42.7±5.0)U/L, respectively, P＜0.05] in Peg-IFN-α-treated group. Conclusion Combination of entecavir and Peg-IFN-α in treatment of patients with serum HBeAg-positive CHB could gain satisfactory serum HBeAg negative and seroconversion rates, and in dominant population might obtain functional cure.

Key words: Hepatitis B, Peginterferon alpha, Entecavir, Therapy, Functional cure

彭麟, 杨春, 李兴泉. 聚乙二醇干扰素α-2b联合恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者疗效研究^*[J]. 实用肝脏病杂志, 2024, 27(5): 677-680.

Peng Lin, Yang Chun, Li Xingquan. Peginterferon alpha and entecavir combination in treatment of patients with serum HBeAg-positive chronic hepatitis B[J]. Journal of Practical Hepatology, 2024, 27(5): 677-680.

参考文献

[1] Veronese P, Dodi I, Esposito S, et al. Prevention of vertical transmission of hepatitis B virus infection. World J Gastroenterol, 2021,27(26):4182-4193.
[2] Chang ML, Liaw YF. HepatitisB flare in hepatitis B e antigen-negative patients: a complicated cascade of innate and adaptive immune responses. Int J Mol Sci,2022,23(3):1552-1553.
[3] 刘嘉城,吴超,李婕.不确定期慢性乙型肝炎病毒感染者的诊疗新进展.中华肝脏病杂志,2024,32(4):370-374.
[4] Hirode G, Choi HSJ, Chen CH,et al. Off-therapy response after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis b: an international, multicenter, multiethnic cohort (retract-B study). Gastroenterology,2022,162(3):757-771.
[5] 姚光弼,张定凤,王宝恩,等.恩替卡韦抗乙型肝炎病毒剂量和疗效的研究.中华肝脏病杂志, 2005, 13(7):484-487.
[6] Wu F, Lu R, Liu Y,et al. Efficacy and safety of peginterferon alpha monotherapy in Chinese inactive chronic hepatitis B virus carriers. Liver Int, 2021,41(9):2032-2045.
[7] 曾文,袁静,刘映霞,等.聚乙二醇干扰素alpha-2a联合恩替卡韦治疗高病毒载量HBeAg阳性慢性乙型肝炎的临床研究.中华实验和临床病毒学杂志, 2013, 27(2):115-118.
[8] 吴凤萍,鲁瑞,刘怡欣,等.核苷(酸)类似物序贯联合聚乙二醇干扰素α治疗血清HBsAg低水平的慢性乙型肝炎患者疗效分析.实用肝脏病杂志, 2021,24(5):677-680.
[9] 中华医学会感染病学分会,中华医学会肝病学分会.慢性乙型肝炎防治指南(2019年版).实用肝脏病杂志, 2020, 23(1):1-24.
[10] Huang D, Wu D, Wang P,et al. End-of-treatment HBcrAg and HBsAb levels identify durable functional cure after Peg-IFN-based therapy in patients with CHB. J Hepatol, 2022,77(1):42-54.
[11] Gehring AJ, Mendez P, Richter K,et al. Immunological biomarker discovery in cure regimens for chronic hepatitis B virus infection, J Hepatol, 2022,77(2):525-538.
[12] 郑志恒,李维筠,回振宇,等.聚乙二醇干扰素α-2a联合恩替卡韦治疗慢性乙型肝炎患者疗效及血清Pygo2和GP73水平变化.实用肝脏病杂志, 2021, 24(1):19-22.
[13] Aliabadi E, Urbanek-Quaing M, Maasoumy B,et al. Impact of HBsAg and HBcrAg levels on phenotype and function of HBV-specific T cells in patients with chronic hepatitis B virus infection. Gut, 2022,71(11):2300-2312.
[14] Chen P, Wei W, Jin L,et al. Efficacy and safety of tenofovir alafenamide fumarate in nucleoside analogue treatment-naïve patients with chronic hepatitis B. Exp Ther Med, 2021,22(5):1325-1326.
[15] Hu Q, Qi X, Yu Y,et al. The efficacy and safety of adding on or switching to peginterferon α-2b in HBeAg-positive chronic hepatitis B patients with long-term entecavir treatment: a multicentre randomised controlled trial. Aliment Pharmacol Ther, 2022,56(9):1394-1407.
[16] van Bommel 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.
[17] Huang Q, Zhou B, Cai D,et al. Rapid Turnover of hepatitis B virus covalently closed circular DNA indicated by monitoring emergence and reversion of signature-mutation in treated chronic hepatitis B patients. Hepatology, 2021,73(1):41-52.
[18] Yoshida K, Enomoto M, Tamori A,et al. Combination of entecavir or tenofovir with pegylated interferon-α for long-term reduction in hepatitis B surface antigen levels: simultaneous, sequential, or add-on combination therapy. Int J Mol Sci, 2021,22(3):1456-1457.
[19] Kim S, Yoo S, Lee JI,et al. Anti-HBc IgG levels: a predictor of HBsAg seroclearance in chronic hepatitis b patients with nucleos(t)ide analogue-induced HBeAg seroclearance. Dig Dis Sci,2022,67(1):321-328.
[20] Zhang Q, Li G, Yu Y,et al. Histological response to combination therapy with nucleos(t)ide analogs and peginterferon alpha in treatment-naïve chronic hepatitis B patients. J Viral Hepat,2019,26(1):59-68.

聚乙二醇干扰素α-2b联合恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者疗效研究^*

Peginterferon alpha and entecavir combination in treatment of patients with serum HBeAg-positive chronic hepatitis B

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