替比夫定与阿德福韦酯联用对慢性乙型肝炎患者肾功能的影响

Effect of telbivudine combined with adefovir on renal function in patients with chronic hepatitis B

目的探讨替比夫定（LdT）与阿德福韦酯（ADV）联用对慢性乙型肝炎（CHB）患者肾功能的影响。方法研究对象为就诊于浙江中医药大学附属第一医院、因LAM耐药联合应用ADV后出现肾功能损伤的CHB患者，研究设计为随机对照试验。用随机数字表法将患者分为继续应用原治疗方案组（LAM＋ADV组）和以LdT替换LAM组（LdT＋ADV组），比较2组患者入组时和治疗第24、48周HBVDNA、丙氨酸转氨酶（ALT）、血清肌酐（Set）、肾小球滤过率估算值（eGFI~）、尿B2微球蛋白（tJl32一MG）和血清肌酸激酶（sCK）水平。结果共79例患者纳入研究，LAM＋ADV组41例，LdT＋ADV组38例。2组患者的性别分布、年龄、体重及人组时各指标检测结果的差异均无统计学意义（均P〉0．05）。48周治疗期间2组均未出现病毒学突破者。2组患者治疗不同时点ALT水平差异均无统计学意义（均P〉0．05）。LAM＋ADV组患者第24、48周Scr水平均高于人组时[（117±11）、（122±12）μmol／L比（113±12）μmol／L]，第48周与入组时比较差异有统计学意义（P〈0．05）；LdT＋ADV组第24、48周Ser水平均低于入组时[（104±10）、（99±9）μmol／L比（109±10）μmol／L，均P〈0．05）。LAM＋ADV组第24、48周eGFR水平均低于入组时[（68．9±12．2）、（66．1±7．6）ml·min-1·1．73m2比（70．9±8．1）m1．min-1·1．73m2]，第48周与入组时比较差异有统计学意义（P〈0．05）；LdT＋ADV组第24、48周eGFR水平均高于入组时[（75．1±11．4）、（79．6±31．1）ml·min-1·1．73m。比（71．4±10．6）ml·min-1·1．73m2，均P〈0．05）。LAM＋ADV组第24、48周Uβ2-MG水平均高于入组时[4611（23920，740）、4719（24109，967）μg/L比4601（23807，611）μg/L]，第48周与入组时比较差异有统计学意义（P〈0．05）。LdT＋ADV组第24、48周Uβ2-MG水平均低于入组时[3251（12890，220）、1950（10119，73）ug/L比4109（24703、633）ug／L]，第48周与人组时比较差异有统计学意义（P〈0．05）。LAM＋ADV组入组时和第24、48周sCK水平[（99±31）、（99±36）、（96±37）U／L]差异无统计学意义（均P〉0．05）。LdT＋ADV组第24、48周sCK水平均高于人组时[（107±38）、（130±56）U／L比（97±31）U／L]。第48周与入组时比较差异有统计学意义（P〈0．05）。2组患者治疗第48周与入组时比较，Set、eGFR、Uβ2-MG和sCK水平差异均有统计学意义（均P〈0．05）。结论LdT＋ADV方案具有改善CHB患者。肾功能的作用，但在治疗过程中应密切关注患者sCK水平的变化。

Objective To explore the effect of combination of telbivudine （LdT） and adefovir dipivoxil （ADV） on renal function in patients with chronic hepatitis B （CHB）. Methods The CHB patients with renal injury due to lamivudine （LAM） resistance and combination with ADV, who visited in First Affiliated Hospital of Zhejiang Chinese Medical University were enrolled into this study. The randomized controlled trial was performed in this study. The patients were divided into two groups by table of random number： the LAM ± ADV group （ original treatment was continued ） and the LdT ± ADV group （LAM was replaced with LdT）. The levels of HBV DNA, alanine aminotransferase （ALT）, serum creatinine （Scr）, estimated glomerular filtration rate （eGFR）, urinary beta 2-microspheres （Ut32-MG）, and serum creatine kinase （sCK） were compared between the 2 groups at baseline, 24 and 48 weeks of treatments. Results A total of 79 patients were enrolled into the study. There were 41 patients in the LAM ± ADV group and 38 in the LdT ± ADV group. The differences of sex distribution, age, body weight and the basal level between the 2 groups were not statistically significant （ all P 〉 0.05 ）. There were no HBV DNA breakthrough in patients during 48 weeks of treatment in both groups. The differences of ALT levels at different time points in patients in the 2 groups were not statistically significant （ all P 〉 0.05 ）. In the LAM ± ADV group, the Scr levels at 24 and 48 weeks of treatment were higher than those at baseline [ （ 117 _± 11）, （ 122 ± 12） ixmol/L vs. （ 113 ± 12） ixmol/L]. The difference between the baseline and 48 weeks of treatment was statistically significant （P 〈 0.05）. The levels of Scr in the LdT ± ADV group at 24 and 48 weeks of treatment were lower than those at baseline [ （ 104 ± 10）, （99 ± 9 ） p^mol/L vs. （ 109 ± 10） Ixmol/L] （ all P 〈 0.05 ）. The levels of eGFR in the LAM ± ADV group at 24 and 48 weeks of treatment were lower than those at baseline[ （68.9 ±12.2）, （66.1 ±7.6）ml ·min-1 1.73 m2 vs. （70.9 ± 8.1 ） ml·min-1·1.73 m-2 ]. The difference between the baseline and 48 weeks of treatment was statistically significant （P 〈 0.05）. The levels of eGFR in the LdT ± ADV group at 24 and 48 weeks of treatment were higher than those at baseline [ （75.1 ± 11.4）, （79.6 ± 31.1） ml ·min-1· 1.73 m-2 vs. （71.4 ± 10.6） ml · min-1· 1.73 m-2 ] （ all P 〈 0.05 ）. The levels of UI32-MG in the group of LAM ± ADV at 24 and 48 weeks of treatment were higher than those at baseline [ 4 611 （23 920, 740）, 4 719 （24 109, 967 ） p,g/L vs. 4 601 （23 807, 611 ） Ixg/L ]. The difference between the baseline and 48 weeks of treatment was statistically significant （P 〈 0.05 ）. The levels of Uβ2- MG in the LdT ± ADV group at 24 and 48 weeks of treatment were lower than those at baseline [ 3 251 （ 12 890,220）, 1 950 （ 10 119, 73） ug/L vs. 4 109 （24 703, 633 ） ug/L ]. The difference between the baseline and 48 weeks of treatment was statistically significant （P 〈 0.05）. The difference of sCK levels between the baseline and 24 and 48 weeks of treatments [ （99 ± 31 ）, （99 ± 36）, （96 ± 37 ） ] were not statistically significant （all P 〉 0.05 ）. The sCK levels in the LdT ± ADV group at 24 and 48 weeks of treatments were higher than those at baseline[ （ 107 ±38）, （ 130 ± 56） U/L vs. （ 97 ± 31 ） U/L ]. The difference between the baseline and 48 weeks of treatment was statistically significant （P 〈 0.05 ）. The differences of Scr, eGFR, UI32-MG, and sCK levels at baseline and 48 weeks of treatment in the 2 groups were statistically significant （ all P 〈 0.05）. Conclusions The therapeutic regimen of telbivudine combination with adefovir dipivoxil can improve the renal function in patients with CHB. The change of sCK level should be monitor closely during the treatment.