干扰素α-2b联合恩替卡韦与干扰素α-2b联合替诺福韦治疗HBeAg阳性慢性乙型肝炎患者疗效比较研究*

doi:10.3969/j.issn.1672-5069.2025.05.004

摘要/Abstract

摘要： 目的分析比较干扰素α-2b联合恩替卡韦(ETV)与干扰素α-2b联合替诺福韦治疗血清HBeAg阳性的慢性乙型肝炎(CHB)患者的疗效。方法 2022年1月～2023年12月我院收治的84例血清HBeAg阳性的CHB患者,被随机分为两组,每组42例,分别给予干扰素α-2b联合ETV或干扰素α-2b联合富马酸替诺福韦(TDF)治疗48 w。采用实时荧光定量PCR法检测血清HBV DNA载量,采用化学发光免疫分析法检测血清HBV标志物,使用全自动生化分析仪检测血生化指标,包括血肌酐(sCr)和β₂微球蛋白(β₂-MG),计算估算的肾小球滤过率(eGFR),使用肝脏瞬时弹性成像仪行肝脏硬度检测(LSM)。结果在治疗48 w末,干扰素α-2b联合TDF治疗组血清HBV DNA阴转率、HBeAg血清学转换率和ALT复常率分别为100.0%、40.5%和100.0%,与干扰素α-2b联合ETV治疗组的100.0%、40.5%和100.0%比,无显著性相差(P>0.05);血清ALT、AST和LSM分别为(31.4±4.9)IU/L、(28.4±4.5)IU/L和(6.9±0.8)kPa,与干扰素α-2b联合ETV治疗组【分别为(33.2±4.5)IU/L、(32.1±4.3)IU/L和(6.5±0.9)kPa】比,差异无统计学意义(P>0.05);两组sCr、血清β₂-MG和eGFR水平比较,差异均无统计学意义(P＞0.05)。结论应用干扰素α-2b联合ETV或TDF治疗血清HBeAg阳性的CHB患者的近期疗效均较好,但后续是否可以停止抗病毒治疗,仍需要观察。

关键词: 慢性乙型肝炎, 干扰素α-2b, 恩替卡韦, 替诺福韦, HBeAg, 治疗

Abstract: Objective The aim of this study was to compare antiviral efficacy of pegylated interferon (peg-IFN)-α2b and entecavir (ETV)or tenofovir combination in the treatment of patients with serum HBeAg-positive chronic hepatitis B (CHB). Methods 84 patients with serum HBeAg-positive CHB were enrolled in our hospital between January 2022 and December 2023, and were randomly assigned to receive peg-IFN-α2b and ETV combination in 42 patients or to receive peg-IFN-α2b and tenofovir disoproxil fumarate (TDF) combination for 48 weeks. Serum HBV DNA loads were detected by real-time fluorescence quantitative PCR, serum HBeAg and HBsAg levels were measured by chemiluminescence immunoassay, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (sCr), β₂-microglobulin (β₂-MG) levels were detected by automatic biochemical analyzer, with estimated glomerular filtration rate (eGFR) calculated by using modified formula of kidney disease. Liver stiffness measurement (LSM) was determined by liver transient elastography. Results By end of 48 weeks of antiviral treatment, serum HBV DNA loss, HBeAg seroconversion and serum ALT normalization rates in peg-IFN-α2b and TDF combination-treated patients were 100.0%, 40.5% and 100.0%, all not significantly different as compared to 100.0%, 40.5% and 100.0% (P>0.05) in peg-IFN-α2b and ETV combination-treated patients; serum ALT, AST and LSM levels were (31.4±4.9)IU/L, (28.4±4.5)IU/L and (6.9±0.8)kPa, all not significantly different compared to [(33.2±4.5)IU/L, (32.1±4.3)IU/L and (6.5±0.9) kPa, P>0.05] in peg-IFN-α2b and ETV combination-treated patients; there were no significant differences as respect to sCr, serum β₂-MG level and eGFR between the two groups (P＞0.05). Conclusion Both peg-IFN-α2b and ETV or TDF combination in the treatment of patients with serum HBeAg-positive CHB have a satisfactory short-term antiviral efficacy, but the long-term outcomes still needs further investigation.

Key words: Hepatitis B, Interferon-α2b, Entecavir, Tenofovir disoproxil fumarate, Hepatitis B virus e antigen, Therapy

丛东威, 刘丽娜, 高文娟, 黄超群. 干扰素α-2b联合恩替卡韦与干扰素α-2b联合替诺福韦治疗HBeAg阳性慢性乙型肝炎患者疗效比较研究^*[J]. 实用肝脏病杂志, 2025, 28(5): 655-658.

Cong Dongwei, Liu Lina, Gao Wenjuan, et al. Antiviral efficacy of pegylated interferon α-2b and entecavir or tenofovir in the treatment of patients with serum HBeAg-positive chronic hepatitis B[J]. Journal of Practical Hepatology, 2025, 28(5): 655-658.

参考文献

[1] Huang DQ, Tran A, Yeh ML, et al. Antiviral therapy substantially reduces HCC risk in patients with chronic hepatitis B infection in the indeterminate phase. Hepatology, 2023, 78(5):1558-1568.
[2] Bonino F, Colombatto P, Brunetto MR. HBeAg-negative/anti-HBe-positive chronic hepatitis B: a 40-year-old history. Viruses, 2022, 14(8):1691-1698.
[3] 张丹,江建新.重组细胞因子基因衍生蛋白与干扰素α-2b分别联合恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者疗效研究.实用肝脏病杂志,2023,26(1):27-30.
[4] 王春莹,屈耀宁,乔炜,等.恩替卡韦治疗慢性乙型肝炎患者血清HBV cccDNA和HBV pgRNA水平变化.实用肝脏病杂志,2022,25(5):641-644.
[5] van Bömmel F, Stein K, Heyne R, et al. A multicenter randomized-controlled trial of nucleos(t)ide analogue cessation in HBeAg-negative chronic hepatitis B. J Hepatol, 2023, 78(5):926-936.
[6] 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.实用肝脏病杂志,2024,27(5):677-680.
[7] 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.
[8] 中国肝炎防治基金会中华医学会感染病学分会中华医学会肝病学分会和中国研究型医院学会肝病专业委员会.瞬时弹性成像技术诊断肝纤维化专家共识(2018年更新版).中华肝脏病杂志,2019,27(3):182-191.
[9] Chan HLY, Buti M, Lim YS, et al. Long-term treatment with tenofovir alafenamide for chronic hepatitis B results in high rates of viral suppression and favorable renal and bone safety. Am J Gastroenterol, 2024, 119(3):486-496.
[10] Choi WM, Yip TC, Wong GL, et al. Hepatocellular carcinoma risk in patients with chronic hepatitis B receiving tenofovir- vs. entecavir-based regimens: Individual patient data meta-analysis. J Hepatol, 2023, 78(3):534-542.
[11] Landovitz RJ, Hanscom BS, Clement ME, et al. Efficacy and safety of long-acting cabotegravir compared with daily oral tenofovir disoproxil fumarate plus emtricitabine to prevent HIV infection in cisgender men and transgender women who have sex with men 1 year after study unblinding: a secondary analysis of the phase 2b and 3 HPTN 083 randomised controlled trial. Lancet HIV, 2023, 10(12):767-778.
[12] Song G, Yang R, Jin Q, et al. HBV pregenome RNA as a predictor of spontanous HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients. BMC Gastroenterol, 2023, 23(1):381-388.
[13] Ghany MG, Buti M, Lampertico P, et al. Guidance on treatment endpoints and study design for clinical trials aiming to achieve cure in chronic hepatitis B and D: Report from the 2022 AASLD-EASL HBV-HDV Treatment Endpoints Conference. Hepatology, 2023, 78(5):1654-1673.
[14] Erken R, Loukachov VV, de Niet A,et al. A prospective five-year follow-up after peg-interferon plus nucleotide analogue treatment or no treatment in HBeAg negative chronic hepatitis B patients. J Clin Exp Hepatol, 2022, 12(3):735-744.
[15] Wang WX, Jia R, Gao YY,et al. Quantitative anti-HBc combined with quantitative HBsAg can predict HBsAg clearance in sequential combination therapy with PEG-IFN-α in NA-suppressed chronic hepatitis B patients. Front Immunol, 2022, 13(1):e894410.
[16] Papatherodoridis G, Lampertico P. HCC risk in patients who are HBeAg-positive and have chronic hepatitis B under long-term nucleos(t)ide analogue therapy: New insights from Asia. Hepatology, 2024, 80(2):260-262.
[17] Butt SRR, Satnarine T, Ratna P, et al. Asystematic review on current trends in the treatment of chronic hepatitis B to predict disease remission and relapse. Cureus, 2022, 14(12):e32247.
[18] Lian J, Kuang W, Jia H,et al. Pegylated interferon-α-2b combined with tenofovir disoproxil fumarate, granulocyte-macrophage colony-stimulating factor, and hepatitis B vaccine treatment for naïve HBeAg-positive chronic hepatitis B patients: A prospective, multicenter, randomized controlled study. J Med Virol, 2022, 94(11):5475-5483.
[19] Brakenhoff SM, de Knegt RJ, Oliveira J, et al. Levels of antibodies to hepatitis B core antigen are associated with liver inflammation and response to peginterferon in patients with chronic hepatitis B. J Infect Dis, 2022, 227(1):113-122.
[20] Kumar K, Jindal A, Gupta E,et al. Long term HBsAg responses to peg-interferon alpha-2b in HBeAg negative chronic hepatitis B patients developing clinical relapse after stopping long-term nucleos(t)ide analogue therapy. J Clin Exp Hepatol, 2024, 14(1):e101272.

干扰素α-2b联合恩替卡韦与干扰素α-2b联合替诺福韦治疗HBeAg阳性慢性乙型肝炎患者疗效比较研究^*

Antiviral efficacy of pegylated interferon α-2b and entecavir or tenofovir in the treatment of patients with serum HBeAg-positive chronic hepatitis B

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