恩替卡韦经治慢性乙型肝炎低病毒血症患者联合或序贯艾米替诺福韦治疗疗效研究*

doi:10.3969/j.issn.1672-5069.2025.03.004

摘要/Abstract

摘要： 目的探讨联合或序贯艾米替诺福韦(TMF)治疗恩替卡韦(ETV)经治的出现低病毒血症(LLV)的慢性乙型肝炎(CHB)患者的疗效。方法 2021年1月～2023年12月我院诊治的CHB患者89例,纳入患者均接受ETV治疗至少24个月以上,检测评估发现完全病毒学应答52例和LLV者37例,给予后者ETV联合TMF(n=14)、停用ETV,改用TMF(n=12)和继续ETV(n=11)治疗48 w。应用二元Logistic多因素回归分析ETV治疗的CHB患者发生LLV的影响因素。结果 LLV组年龄、血清ALT和AST水平分别为(36.0±5.2)岁、(54.2±7.0)U/L和(43.5±7.4)U/L,均显著小于或低于CVR组【分别为(38.9±5.8)岁、(143.0±6.8)U/L和(85.4±7.1)U/L,P<0.05】,而血清HBV DNA、HBeAg阳性率、HBsAg水平和LSM分别为(7.2±2.6)lg IU/ml、82.7%、6300.8(5123.9,8912.4)IU/ml和(8.6±1.0)kPa,均显著高于CVR组【分别为(5.4±1.4)lg IU/ml、40.5%、3002.0(2413.4,4512.4)IU/ml和(7.1±0.7)kPa,P<0.05】;多因素Logistic回归分析显示,血清HBV DNA高载量、HBeAg阳性和血清HBsAg定量水平高均是发生LLV的独立危险因素(P<0.05);在挽救抗病毒治疗48 w末,联合组血清HBV DNA全部转阴,血清ALT和LSM分别为(35.1±4.7)U/L和(6.9±0.6)kPa,均显著优于其他两组(P<0.05)。结论 ETV经治的CHB患者可能发生LLV,而采取ETV联合TMF挽救治疗能获得满意的抗病毒治疗效果,值得长期观察。

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

Abstract: Objective The purpose of this study was to investigate sequential or combined rescue antiviral therapy by tenofovir amibufenamide (TMF) in entecavir(ETV)-treated chronic hepatitis B (CHB) patients with low-level viremia(LLV). Methods Eighty-nine patients with CHB who had ETV treatment for at least 24 months were encountered in our hospital between January 2021 and December 2023, and high-sensitive PCR detection found complete virological response (CVR) in 52 cases and LLV in 37 cases. For rescue antiviral therapy, ETV and TMF combination was given in 14 patients, switching to TMF in 12 patients and continuation on ETV in 11 patients for 48 weeks. Multivariate Logistic regression analysis was applied to find risk factors for LLV occurrence. Results Baseline serum ALT and AST levels in patients with LLV were (36.0±5.2)yr, (54.2±7.0)U/L and (43.5±7.4)U/L, all much younger or lower than [(38.9±5.8)yr, (143.0±6.8)U/L and (85.4±7.1)U/L, respectively, P<0.05], while serum HBV DNA load, HBeAg positive rate, HBsAg level and liver stiffness measurement (LSM) were (7.2±2.6)lg IU/ml, 82.7%, 6300.8(5123.9, 8912.4)IU/ml and (8.6±1.0)kPa, all much higher than [(5.4±1.4)lg IU/ml, 40.5%, 3002.0(2413.4, 4512.4)IU/ml and (7.1±0.7)kPa, respectively, P<0.05] in those with CVR; multivariate Logistic regression analysis showed that high serum HBV DNA loads, serum HBeAg positive and high serum HBsAg levels were all the independent risk factors for occurrence of LLV (P<0.05) in CHB patients receiving ETV antiviral treatment; by end of 48 week rescue therapy, serum HBV DNA transferred to negative, serum ALT and LSM were (35.1±4.7)U/L and (6.9±0.6)kPa in patients with ETV and TMF combination treatment, much superior to in other two groups (P<0.05). Conclusion LLV could occur in CHB patients receiving ETV antiviral therapy, and combination of ETV and TMF is an efficacious choice for rescue therapy, which needs long-term clinical observation.

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

孔丽霞, 陈旭峰, 许艳, 周建飞, 孙舒. 恩替卡韦经治慢性乙型肝炎低病毒血症患者联合或序贯艾米替诺福韦治疗疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(3): 334-337.

Kong Lixia, Chen Xufeng, Xu Yan, et al. Sequential or combined rescue antiviral therapy by tenofovir amibufenamide in entecavir-treated chronic hepatitis B patients with low-level viremia[J]. Journal of Practical Hepatology, 2025, 28(3): 334-337.

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恩替卡韦经治慢性乙型肝炎低病毒血症患者联合或序贯艾米替诺福韦治疗疗效研究^*

Sequential or combined rescue antiviral therapy by tenofovir amibufenamide in entecavir-treated chronic hepatitis B patients with low-level viremia

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