替诺福韦补救治疗rtM204位点突变的慢性乙型肝炎患者效果研究

doi:10.3969/j.issn.1672-5069.2021.03.008

摘要/Abstract

摘要： 目的探讨应用替诺福韦补救治疗核苷(酸)类经治的rtM204位点突变的慢性乙型肝炎(CHB)患者的效果。方法 2016年4月～2019年2月我院收治的94例经阿德福韦酯或拉米夫定治疗失败的且经检测为rtM204位点突变的CHB患者,将患者分为两组,分别接受替诺福韦治疗47例和恩替卡韦治疗47例,观察18个月。采用实时荧光定量PCR法检测血清HBV DNA载量,使用全自动生化分析仪检测血肌酐(sCr),并计算内生肌酐清除率(Crcl),采用ELISA法检测血清HBsAg和HBeAg,使用流式细胞仪检测外周血T淋巴细胞CD3⁺和CD4⁺百分比。结果在治疗6 m、12 m和18 m,替诺福韦治疗组血清HBV DNA转阴率分别为66.0%、76.6%和93.6%,均显著高于恩替卡韦治疗组的38.3%、55.3%和78.7%(P均＜0.05);在治疗18 m,替诺福韦治疗组血清HBeAg转阴率为12.8%,显著高于恩替卡韦治疗组(0.0%,P＜0.05);在治疗6 m和18 m,替诺福韦组血清AST水平分别为(50.2±8.1)U/L和(31.7±6.9)U/L,显著低于恩替卡韦治疗组[(57.7±8.3)U/L和(38.4±7.1)U/L,P＜0.05];在治疗6 m、12 m和18 m,替诺福韦治疗组外周血CD3⁺细胞百分比分别为(31.6±5.2)%、(38.1±5.7)%和(40.2±6.2)%,与恩替卡韦治疗组比,无显著性差异[(32.1±5.5)%、(37.6±5.8)%和(39.1±5.9)%,P＞0.05],CD4⁺细胞百分比分别为(28.6±3.9)%、(31.2±5.3)%和(36.1±5.7)%,与恩替卡韦治疗组比,无显著性差异[(29.3±3.7)%、(32.4±5.9)%和(34.5±5.3)%,P＞0.05],Crcl分别为(103.4±39.3)mL/min、(101.2±30.2)mL/min和(97.6±23.8)mL/min,与恩替卡韦治疗组比,无显著性差异【(106.7±40.1)mL/min、(103.5±31.6)mL/min和(99.5±25.4)mL/min,P＞0.05】。结论应用替诺福韦补救治疗rtM204位点突变的CHB患者可快速抑制病毒复制,稳定肝功能,可能比应用恩替卡韦效果好。

关键词: 慢性乙型肝炎, rtM204突变, 替诺福韦, 补救治疗

Abstract: Objective The aim of this study was to investigate the efficacy of tenofovir rescue therapy for patients with chronic hepatitis B (CHB) and rtM204 mutation.Methods 94 patients with CHB who had failed to adefovir or lamivudine therapy with confirmed rtM204 mutation were enrolled in our hospital between April 2016 and February 2019, and were randomly divided into two groups, receiving tenofovir in 47 cases, or entecavir in 47 cases for rescue therapy for 18 months. Serum HBV DNA, HBsAg and HBeAg, and creatinine clearance (Crcl) were obtained. The peripheral blood CD3⁺ and CD4⁺ cell percentages were detected by FCM.Results At the end of 6, 12 and 18 month observation, serum HBV DNA loss in tenofovir-treated patients were 66.0%, 76.6% and 93.6%, all significantly higher than 38.3%, 55.3% and 78.7%(all P＜0.05) in entecavir-treated patients; at the end of 18 month, serum HBeAg negative rate in tenofovir-treated patients was 12.8%, much higher than that in entecavir-treated patients (0.0%, P＜0.05); at the end of 6 month and 18 month, serum AST levels in tenofovir-treated patients were (50.2±8.1)U/L and (31.7±6.9)U/L, significantly lower than [(57.7±8.3)U/L and (38.4±7.1)U/L, P＜0.05] in entecavir-treated patients; at 6 month, 12 month and 18 month observation, the percentages of CD3⁺ cells in tenofovir-treated patients were (31.6±5.2)%, (38.1±5.7)% and (40.2±6.2)%, not significantly different compared to [(32.1±5.5)%, (37.6±5.8)% and (39.1±5.9)%, P＞0.05], that of CD4⁺ cells were(28.6±3.9)%, (31.2±5.3)% and (36.1±5.7)%, not significantly different compared to [(29.3±3.7)%, (32.4±5.9)% and (34.5±5.3)%, P＞0.05], and Crcl were (103.4±39.3)mL/min, (101.2±30.2)mL/min and (97.6±23.8)mL/min, not significantly different compared to [(106.7±40.1)mL/min, (103.5±31.6)mL/min and (99.5±25.4)mL/min, respectively, P＞0.05] in entecavir-treated patients.Conclusion The administration of tenofovir for rescue therapy of patients with rtM204 mutation thanks to failed antiviral treatment might have a better efficacy, superior to entecavir, and warrants further and long-term investigation.

Key words: Hepatitis B, Tenofovir, rtM204 mutation, Rescue therapy

徐文婷, 张继红, 韦冬珏, 李巍. 替诺福韦补救治疗rtM204位点突变的慢性乙型肝炎患者效果研究[J]. 实用肝脏病杂志, 2021, 24(3): 335-338.

Xu Wenting, Zhang Jihong, Wei Dongjue, et al. Efficacy of tenofovir rescue therapy for patients with chronic hepatitis B and rtM204 mutation[J]. Journal of Practical Hepatology, 2021, 24(3): 335-338.

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