替诺福韦酯治疗对慢性乙型肝炎患者血清FGF-23、β_2-MG、Cys-C及RBP水平的影响
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摘要
目的:研究替诺福韦酯治疗对慢性乙型肝炎患者血清成纤维细胞生长因子-23(FGF-23)、β_2-微球蛋白(β_2-MG)、胱抑素-C(Cys-C)及视黄醇结合蛋白(RBP)水平的影响。方法:抽取2015年1月至2016年1月在本院治疗的80例慢性乙型肝炎患者作为研究对象,予服用替诺福韦酯,300 mg/次,1次/d,治疗12个月,抽取40例健康体检者作为对照组。观察患者在不同时间点HBV-DNA水平、HBV-DNA不可检测率、HBe Ag转阴率及血清中FGF-23、β_2-MG、Cys-C及RBP浓度水平变化情况。结果:与治疗前相比较,经过替诺福韦酯治疗后,患者HBV-DNA水平明显下降(P<0.05),HBV-DNA不可检测率明显上升(P<0.05),HBe Ag转阴率明显升高(P<0.05);治疗后6个月、12个月,病例组患者血清中FGF-23、β_2-MG、Cys-C及RBP浓度水平明显高于对照组(均P<0.05);病例组患者血清中FGF-23浓度水平与β_2-MG、Cys-C及RBP浓度水平呈正相关(r:0.566,0.643,0.604,P<0.05),β_2-MG、Cys-C、RBP指标之间也呈正相关(P<0.05)。FGF-23、β_2-MG、Cys-C及RBP指标异常组和对照组比较,BNU、Ccr、GFR、P水平差异具有统计学意义(t值分别为:5.581,6.947,3.330,4.921,均P<0.05),Scr比较差异无统计学意义(P>0.05)。结论:替诺福韦酯对乙型肝炎患者FGF-23、β_2-MG、Cys-C及RBP水平具有升高作用,通过监测这些指标的变化,有助于调整替诺福韦酯治疗方案,预防或减少肾功能不全和低磷性骨病的发生。
AIM:To study the effect of Tenofovir disoproxil fumarate on serum growth factor-23(FGF-23),beta 2-micro-globulin(β_2-MG),cystatin-C(Cys-C)and retinol binding protein(RBP) l level in patients with chronic hepatitis B.METH-ODS:Eighty patients with chronic hepatitis B admitted to our hospital from January in 2015 to January 2016 were included as the treatment group,which was given 12 months of treatment of tenofovir(300 mg/time,1 time/d).Another forty healthy subjects were selected as the control group.Levels of HBV-DNA,HBV-DNA non-detectable rate,HBe Ag negative conversion rate and serum levels of FGF-23,β_2-MG,Cys-C and RBP at different time points were observed and compared.RESULTS:Compared with before treatment,the level of HBV-DNA decreased significantly(P<0.05),HBV-DNA non-detectable and the negative rate of HBe Ag increased significantly(P<0.05)after treatment;the serum level of FGF-23,β_2-MG,Cys-C,and RBP levels were significantly increased than those of the control group(P<0.05)after six-month and twelve-month treatment;the serum concentration of FGF-23 was positively correlated with the level of β_2-MG,Cys-C and RBP concentrations(r:0.566,0.643,0.604,P<0.05),β_2-MG,Cys-C and RBP index also showed positive correlation(P<0.05).Compared with the control group,group of abnormal FGF-23,β_2-MG,Cys-C and RBP presented statistical significance regarding level of BNU,Ccr,GFR,P(t=5.581,6.947,3.330,4.921,P<0.05),yet no significant difference of Scr was observed(P>0.05).CONCLUSION:Tenofovir can increase the levels of FGF-23,β_2-MG,Cys-C and RBP of patients with chronic hepatitis B.Monitoring these indicators can be referential for adjusting treatment to prevent or reduce the occurrence of renal insufficiency and low phosphorus bone disease.
AIM:To study the effect of Tenofovir disoproxil fumarate on serum growth factor-23(FGF-23),beta 2-micro-globulin(β_2-MG),cystatin-C(Cys-C)and retinol binding protein(RBP) l level in patients with chronic hepatitis B.METH-ODS:Eighty patients with chronic hepatitis B admitted to our hospital from January in 2015 to January 2016 were included as the treatment group,which was given 12 months of treatment of tenofovir(300 mg/time,1 time/d).Another forty healthy subjects were selected as the control group.Levels of HBV-DNA,HBV-DNA non-detectable rate,HBe Ag negative conversion rate and serum levels of FGF-23,β_2-MG,Cys-C and RBP at different time points were observed and compared.RESULTS:Compared with before treatment,the level of HBV-DNA decreased significantly(P<0.05),HBV-DNA non-detectable and the negative rate of HBe Ag increased significantly(P<0.05)after treatment;the serum level of FGF-23,β_2-MG,Cys-C,and RBP levels were significantly increased than those of the control group(P<0.05)after six-month and twelve-month treatment;the serum concentration of FGF-23 was positively correlated with the level of β_2-MG,Cys-C and RBP concentrations(r:0.566,0.643,0.604,P<0.05),β_2-MG,Cys-C and RBP index also showed positive correlation(P<0.05).Compared with the control group,group of abnormal FGF-23,β_2-MG,Cys-C and RBP presented statistical significance regarding level of BNU,Ccr,GFR,P(t=5.581,6.947,3.330,4.921,P<0.05),yet no significant difference of Scr was observed(P>0.05).CONCLUSION:Tenofovir can increase the levels of FGF-23,β_2-MG,Cys-C and RBP of patients with chronic hepatitis B.Monitoring these indicators can be referential for adjusting treatment to prevent or reduce the occurrence of renal insufficiency and low phosphorus bone disease.
引文
[1]Agarwal K,Fung SK,Nguyen TT,et al.Twenty-eight day safety,antiviral activity,and pharmacokinetics of tenofovir alafenamide for treatment of chronic hepatitis B infection[J].J Hepatol,2015,62(3):533-540.
[2]杨晓艳,孙长宇,袁翔,等.阿德福韦酯治疗慢性乙型肝炎致低磷血症的临床分析[J].临床肝胆病杂志,2015,31(12):2047-2050.
[3]何佳,宁会彬,曾艳丽,等.血清中β2微球蛋白、视黄醇结合蛋白、胱抑素C在替诺福韦或恩替卡韦单药治疗慢性乙型肝炎早期肾功能变化中的意义[J].中华肝脏病杂志,2016,24(9):643-646.
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[5]吕莹,陈晓蓉.PEG-IFNα-2a治疗HBe Ag阳性慢性乙型肝炎48周应答不佳患者序贯替诺福韦酯24周疗效分析[J].临床肝胆病杂志,2016,32(11):2066-2069.
[6]Buti M,Gane E,Seto WK,et al.Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBe Ag-negative chronic hepatitis B virus infection:a randomised,double-blind,phase 3,non-inferiority trial[J].Lancet Gastroenterol Hepatol,2016,1(3):196-206.
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[8]李晴,王巍,刘琳,等.CKD患者血清FGF-23和血钙、血磷水平与左心功能关系的研究[J].北京医学,2015,37(1):54-56.
[9]史东艳,闫彩凤.成纤维细胞生长因子23与维生素D的相互调节研究进展[J].山东医药,2014,54(24):101-103.
[10]向代军,张洪瑞,白洁,等.血清胱抑素C与β2微球蛋白在慢性肾病新分期中的检测与意义[J].检验医学与临床,2014,11(6):721-722.
[11]张明,王喜青,李成,等.半胱氨酸蛋白酶抑制剂C在糖尿病患者肾脏功能评价中的应用[J].标记免疫分析与临床,2016,23(6):600-602.
[12]刘红,陆晨,刘颖,等.慢性肾脏病患者血、尿视黄醇结合蛋白和血、尿胱抑素C的表达及其临床意义[J].中国综合临床,2014,30(5):464-466.
[13]骆佩怡,唐正运,刘伟东.替诺福韦酯单用治疗慢性乙型肝炎的临床疗效研究[J].中国全科医学,2015,18(34):4216-4219.
[14]Murakami E,Tsuge M,Hiraga N,et al.Effect of tenofovir disoproxil fumarate on drug-resistant HBV clones[J].J Infect,2015,72(1):91-102.
[15]李静,徐彤彤,余帆.联合检测血清IMD、FGF23及Cys C对高血压早期肾功能损伤的评估价值[J].广东医学,2015,53(7):1098-1102.
[16]赵康路,郭秋芳,叶卫江.单用或联合使用阿德福韦酯引起尿β2-微球蛋白改变的研究[J].浙江临床医学,2016,18(2):253-255.
[17]官丽倩,张仁芳.替诺福韦酯相关性肾毒性的研究进展[J].世界临床药物,2014,35(7):444-447.
[2]杨晓艳,孙长宇,袁翔,等.阿德福韦酯治疗慢性乙型肝炎致低磷血症的临床分析[J].临床肝胆病杂志,2015,31(12):2047-2050.
[3]何佳,宁会彬,曾艳丽,等.血清中β2微球蛋白、视黄醇结合蛋白、胱抑素C在替诺福韦或恩替卡韦单药治疗慢性乙型肝炎早期肾功能变化中的意义[J].中华肝脏病杂志,2016,24(9):643-646.
[4]王贵强,王福生,成军,等.慢性乙型肝炎防治指南(2015年版)[J].中国肝脏病杂志电子版,2015,9(3):1-18.
[5]吕莹,陈晓蓉.PEG-IFNα-2a治疗HBe Ag阳性慢性乙型肝炎48周应答不佳患者序贯替诺福韦酯24周疗效分析[J].临床肝胆病杂志,2016,32(11):2066-2069.
[6]Buti M,Gane E,Seto WK,et al.Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBe Ag-negative chronic hepatitis B virus infection:a randomised,double-blind,phase 3,non-inferiority trial[J].Lancet Gastroenterol Hepatol,2016,1(3):196-206.
[7]Murakami E,Wang T,Park Y,et al.Implications of efficient hepatic delivery by tenofovir alafenamide(GS-7340)for hepatitis B virus therapy[J].Antimicrob Agents Chemother,2015,59(6):3563-3569.
[8]李晴,王巍,刘琳,等.CKD患者血清FGF-23和血钙、血磷水平与左心功能关系的研究[J].北京医学,2015,37(1):54-56.
[9]史东艳,闫彩凤.成纤维细胞生长因子23与维生素D的相互调节研究进展[J].山东医药,2014,54(24):101-103.
[10]向代军,张洪瑞,白洁,等.血清胱抑素C与β2微球蛋白在慢性肾病新分期中的检测与意义[J].检验医学与临床,2014,11(6):721-722.
[11]张明,王喜青,李成,等.半胱氨酸蛋白酶抑制剂C在糖尿病患者肾脏功能评价中的应用[J].标记免疫分析与临床,2016,23(6):600-602.
[12]刘红,陆晨,刘颖,等.慢性肾脏病患者血、尿视黄醇结合蛋白和血、尿胱抑素C的表达及其临床意义[J].中国综合临床,2014,30(5):464-466.
[13]骆佩怡,唐正运,刘伟东.替诺福韦酯单用治疗慢性乙型肝炎的临床疗效研究[J].中国全科医学,2015,18(34):4216-4219.
[14]Murakami E,Tsuge M,Hiraga N,et al.Effect of tenofovir disoproxil fumarate on drug-resistant HBV clones[J].J Infect,2015,72(1):91-102.
[15]李静,徐彤彤,余帆.联合检测血清IMD、FGF23及Cys C对高血压早期肾功能损伤的评估价值[J].广东医学,2015,53(7):1098-1102.
[16]赵康路,郭秋芳,叶卫江.单用或联合使用阿德福韦酯引起尿β2-微球蛋白改变的研究[J].浙江临床医学,2016,18(2):253-255.
[17]官丽倩,张仁芳.替诺福韦酯相关性肾毒性的研究进展[J].世界临床药物,2014,35(7):444-447.