恩替卡韦与富马酸替诺福韦酯治疗对慢性乙型肝炎患者肾功能的影响

Effects of entecavir and tenofovir dipivoxil fumarate on renal function in patients with chronic hepatitis B

目的 观察无明显肾功能损害慢性乙型肝炎(chronic hepatitis B,CHB)患者采用恩替卡韦(entecavir, ETV)、富马酸替诺福韦酯(tenofovir disoproxil fumarate, TDF)单药治疗对肾功能的影响。方法 选取保定市第四中心医院2020年1月~2021年12月接受抗病毒治疗的CHB患者,根据患者基线肾小球滤过率估计值(estimated glomerular filtration rate, EGFR)水平分为eGFR> 90 ml/(min·1.73 m^(2))组(n=79)和60~90 ml/(min·1.73 m^(2))组(n=38),分别比较ETV和TDF治疗效果,并对治疗24和48周后的肾小球滤过率eGFR、尿视黄醇结合蛋白(retinol-binding protein, RBP)、α1微球蛋白(α1-microglobulin, α1-MG)和β2微球蛋白(β2-microglobulin, β2-MG)进行比较。结果 治疗前,eGFR> 90 ml/(min·1.73 m^(2))组和60~90 ml/(min·1.73 m^(2))组患者血清谷丙转氨酶(ALT)、乙型肝炎病毒表面抗原(HBSAG)、乙型肝炎病毒(HBV)DNA差异无统计学意义(P> 0.05)。治疗后,eGFR> 90 ml/(min·1.73 m^(2))组和60~90 ml/(min·1.73 m^(2))组不同治疗用药患者患者ALT、HBsAg均下降,与治疗前比较,差异有统计学意义(t=12.234、10.313、3.802、3.604,9.431、7.419、3.508、4.147,P<0.05)。治疗48周后,ALT、HBsAg水平及HBV DNA病毒应答率差异均无统计学意义(P> 0.05)。入组时两组eGFR、尿RBP、α1-MG和β2-MG比较,差异无统计学意义(P> 0.05)。治疗24和48周后,两组组间eGFR、尿RBP、β2-MG差异及与入组时比较差异均无统计学意义(P> 0.05)。eGFR> 90 ml/(min·1.73 m^(2))患者治疗前后及ETV、TDF治疗24周、48周后α1-MG差异无统计学意义(P> 0.05),eGFR60~90 ml/(min·1.73 m^(2))患者24周后α1-MG差异无统计学意义(P> 0.05),48周后TDF组α1-MG高于ETV组也高于入组时,差异有统计学意义(t=2.169、2.859,P<0.05)。结论 恩替卡韦与替诺福韦酯均可有效抑制慢性乙型肝炎患者HBV DNA复制,对于eGFR <90 ml/(min·1.73 m^(2))患者,建议选择恩替卡韦以减少对肾小管的早期损伤。

Objective To observe the effect of monotherapy with entecavir(ETV)and tenofovir disoproxil fumarate(TDF)on renal function in patients with chronic hepatitis B(CHB)without obvious impairment of renal function.Methods CHB patients who received antiviral treatment from January 2020 to December 2021 were divided into subgroups with eGFR>90 ml∕(min·73 m2)and 60~90 ml∕(min·73 m2)based on their baseline eGFR levels.The therapeutic effects of ETV and TDF were compared respectively in subgroups.The levels of glomerular filtration rate(eGFR),urinary retinol binding protein(RBP),a1-microglobulin(a 1-MG),andβ2-microglobulin(β2-MG)were compared after 24 and 48 weeks of treatment.Results Before treatment,there was no statistically significant difference in ALT,HBsAg,and HBV DNA between subgroup(P>0.05).After treatment,both ALT and HBsAg decreased(t=12.234,10.313,3.802,3.604,9.431,7.419,3.508,4.147,P<0.05).There was no statistically significant difference in ALT,HBsAg levels and HBV DNA viral response rate after 48 weeks of treatment with ETV and TDF(P>0.05).When comparing the eGFR,urinary RBP,α1-MG andβ2-MG of each group at the time of enrollment,there was no statistically significant difference(P>0.05).There was no statistically significant differences in eGFR,urinary RBP,andβ2-MG between each subgroup after 24 and 48 weeks of treatment and compared with the time of enrollment(P>0.05).There was no statistically significant difference inα1-MG levels in patients with eGFR>90 ml∕(min·1.73 m^(2))before and after treatment and after 24 weeks and 48 weeks of ETV and TDF treatment(P>0.05).There was no statistically significant difference inα1-MG levels in patients with eGFR60~90 ml∕(min·1.73 m^(2))after 24 weeks.After 48 weeks,theα1-MG concentration in the TDF group was higher than that in the ETV group and higher than at enrollment(t=2.169,2.859,P<0.05).Conclusion Both entecavir and tenofovir disoproxil can effectively inhibit HBV DNA replication in patients with chronic hepatitis B.For patients with eGFR<90 ml∕(min·1.73 m^(2)),it is recommended to choose entecavir to reduce early damage to renal tubules.