阿德福韦酯分别联合恩替卡韦或替诺福韦治疗rtA181V/T单位点突变的慢性乙型肝炎患者疗效初步研究

Rescued therapy of patients with chronic hepatitis B and rtA181V/T mutation by adefovir dipivoxiland entecavir or tenofovir combination

目的研究应用阿德福韦酯(ADV)分别联合替诺福韦(TDF)或恩替卡韦(ETV)治疗rtA181V/T单位点突变的慢性乙型肝炎(CHB)患者的疗效。方法2017年1月~2020年1月我院感染病科收治的50例rtA181V/T单位点突变的CHB患者被随机分为ADV联合TDF治疗25例和ADV联合ETV治疗25例,治疗观察48 w。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生化指标,包括β2-微球蛋白(β2-MG)和视黄醇结合蛋白(RBP),并计算估算的肾小球滤过率(eGFR)和内生肌酐清除率(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淋巴细胞亚群。结果在治疗24 w和48 w,ADV联合TDF治疗组血清HBV DNA转阴率分别为100.0%和100.0%,与ADV联合ETV治疗组(分别为96.0%和96.0%)比,无显著性差异(P>0.05);血清AST水平分别为(49.2±5.5)U/L和(30.4±4.0)U/L,显著低于ADV联合ETV治疗组【分别为(55.3±7.0)U/L和(43.2±6.8)U/L,P<0.05】,血清ALT水平分别为(40.3±6.1)U/L和(39.1±4.3)U/L,显著低于ADV联合ETV治疗组【分别为(65.1±7.5)U/L和(45.3±6.1)U/L,P<0.05】,血清HBV DNA水平分别为(0.8±0.2)lg IU/mL和(2.0±0.4)lg IU/mL,显著低于ADV联合ETV治疗组【分别为(2.9±0.3)lg IU/mL和(1.2±0.2)lg IU/mL,P<0.05】;外周血CD4^(+)细胞百分比分别为(45.2±3.6)%和(48.3±4.2)%,CD4^(+)/CD8^(+)细胞比值分别为(1.4±0.2)和(1.8±0.1),显著高于ADV联合ETV治疗组【分别为(42.4±3.1)%和(45.0±3.2)%,和(1.2±0.1)和(1.5±0.1),P<0.05】;在观察期内,两组肾功能指标无显著性变化。结论应用ADV联合TDF治疗rtA181V/T单位点突变的CHB患者近期效果较好,能够快速抑制病毒复制,稳定肝功能,对肾功能影响较小。

Objective The aim of this study was to investigate the short-term efficacy of adefovir dipivoxil(ADV)and entecavir(ETV)or tenofovir(TDF)combination rescued therapy in patients with chronic hepatitis B and rtA181V/T mutation.Methods Fifty patients with CHB and rtA181V/T mutation were admitted to the Department of Infectious Diseases in our hospital between January 2017 and January 2020,and were divided randomly into two groups,receiving ADV and TDF or ADV and ETV treatment,with 25 cases in each.Serum HBV DNA loads was assayed by real-time fluorescent quantitative PCR.Serum β2-microglobulin(β2-MG),retinol-binding protein(RBP)and serum creatinine(sCr)were detected,and creatinine clearance(Crcl)and estimaated glomerular filtration rate(eGFR)were calculated.Peripheral blood T lymphocytes were performed by flow cytometry.Results At the end of 24-week and 48-week,serum HBV DNA negative rate in patients receiving ADV and TDF combination treatment were 100.0% and 100.0%,not significantly different compared to 96.0% and 96.0%,respectively,in ADV and ETV combination-treated patients(P>0.05);serum AST levels were(49.2±5.5)U/L and(30.4±4.0)U/L,significantly lower than[(55.3±7.0)U/L and(43.2±6.8)U/L,respectively,P<0.05],serum ALT levels were(40.3±6.1)U/L and(39.1±4.3)U/L,significantly lower than[(65.1±7.5)U/L and(45.3±6.1)U/L,P<0.05],and serum HBV DNA loads were(0.8±0.2)lg IU/mL and(2.0±0.4)lg IU/mL,significantly lower than[(2.9±0.3)lg IU/mL and(1.2±0.2)lg IU/mL,respectively,P<0.05]in ADV and ETV combination-treated patients;the percentages of peripheral blood CD4^(+)cells were(45.2±3.6)% and(48.3±4.2)%,and the ratios of CD4^(+)/CD8^(+)cells were(1.4±0.2)and(1.8±0.1),significantly higher than[(42.4±3.1)% and(45.0±3.2)%,and(1.2±0.1)and(1.5±0.1),respectively,P<0.05]in ADV and ETV combination-treated patients;there was no significant changes of renal function tests in the two groups.Conclusion The short-term efficacy of ADV and TDF combination therapy in patients with CHB and rtA181V/T mutation is good,with the rapid inhibition of viral replication and stable liver function tests without side effects.