替比夫定联合阿德福韦酯对失代偿期乙型肝炎肝硬化患者肝肾功能的影响

Effect of telbivudine combined with adefovir dipivoxil on liver and kidney function in patients with decompensated hepatitis B cirrhosis

目的探讨替比夫定(LDT)联合阿德福韦酯(ADV)对失代偿期乙型肝炎(乙肝)肝硬化患者肝肾功能的影响。方法选取2017年1月至12月在肝病科就诊的100例乙肝肝硬化患者,用随机数字表法分为拉米夫定(LAM)+ADV组(50例)和LDT+ADV组(50例)。LAM+ADV组给予LAM+ADV进行治疗,LDT+ADV组给予LDT+ADV进行治疗,随访1年。观察并比较两组患者的肝功能、肾功能、肾损伤标志物以及乙肝病毒脱氧核糖核酸(HBV-DNA)转阴率。结果治疗前、治疗24周、治疗48周时比较,两组的丙氨酸氨基转移酶(ALT)、总胆红素(Tbil)、白蛋白(ALB)、尿素氮(BUN)、Child-Pugh评分无明显统计学差异(P>0.05)。治疗24周,LAM+ADV组肾小球滤过率(EGFR)为(100.5±9.3)ml·min^-1·1.73 m^-2,显著低于LDT+ADV组的(107.6±11.2)ml·min^-1·1.73 m^-2(P<0.05);血肌酐(Scr)为(90.9±8.5)μmol/L,显著高于LDT+ADV组的(79.4±7.1)μmol/L(P<0.05)。治疗48周,LAM+ADV组EGFR为(95.0±8.7)ml·min^-1·1.73 m^-2,显著低于LDT+ADV组的(117.8±12.0)ml·min^-1·1.73 m^-2(P<0.05);Scr为(108.7±9.2)μmol/L,显著高于LDT+ADV组的(70.6±6.4)μmol/L(P<0.05)。治疗48周,LAM+ADV组尿神经导向因子-1为(192.8±19.2)μg/L,显著高于LDT+ADV组的(187.6±17.1)μg/L(P<0.05)。治疗24周时,LDT+ADV组、LAM+ADV组HBV-DNA转阴率分别为82.0%和72.0%;治疗48周时,LDT+ADV组、LAM+ADV组HBV-DNA转阴率分别为94.0%和88.0%,差异均无统计学意义(P>0.05)。结论 LDT+ADV与LAM+ADV对失代偿期乙肝肝硬化患者治疗过程中,对肝功能及HBV-DNA转阴率的影响相差不大,但前者具有更好的肾保护功能,值得临床进一步研究。

Objective To investigate the effect of combination of telbivudine(LDT) and adefovir dipivoxil(ADV) on liver and kidney function in patients with decompensated hepatitis B cirrhosis.Methods A total of 100 patients with hepatitis B cirrhosis who were treated in Department of Hepatology from January to December 2017 were randomly divided into lamivudine(LAM)+ADV group and LDT+ADV group(n=50,each).LAM+ADV group was treated with LAM+ADV,LDT+ADV group was treated with LDT+ADV.All the patients were followed up for 1 year.The liver function,renal function,markers of renal injury and the negative rate of HBV-DNA were observed and compared between the two groups.Results There was no significant difference in alanine aminotransferases(ALT),total bilirubin(TBIL),albumin(ALB),urea nitrogen(BUN) and Child-Pugh score between the two groups before treatment,24-week and 48-week of treatment(all P>0.05). After 24-week of treatment,the glomerular filtration rate(EGFR) in LAM+ADV group was significantly lower than that in LDT+ADV group [(100.5±9.3) ml·min^-1·1.73 m^-2 vs(107.6±11.2) ml·min^-1·1.73 m^-2,P<0.05],and the serum creatinine(Scr) was significantly higher than that of LDT+ADV group [(90.9±8.5) μmol/L vs(79.4±7.1) μmol/L,P<0.05].At 48-week of treatment,the EGFR in LAM+ADV group was significantly lower than that in LDT+ADV group [(95.0±8.7) ml·min^-1·1.73 m^-2 vs(117.8±12.0)ml·min^-1·1.73 m^-2,P<0.05],and the Scr was significantly higher than that in LDT+ADV group [(108.7±9.2) μmol/L vs(70.6±6.4)μmol/L,P<0.05]. At 48-week of treatment,the urinary neurotransmitter-1(Netrin-1) in LAM+ADV group was significantly higher than that in LDT+ADV group [(192.8±19.2)μg/L vs(187.6±17.1)μg/L,P<0.05].At 24-week of treatment,the negative rate of HBV-DNA in LDT+ADV group and LAM+ADV group was 82.0% and 72.0%,respectively.At 48 weeks of treatment,the negative rate of HBV-DNA in LDT+ADV group and LAM+ADV group was 94.0% and 88.0%,respectively,and there was no significant difference between two groups at each time point(all P>0.05).Conclusion Both LDT + ADV and LAM + ADV have little effect on liver function and HBV-DNA negative conversion rate in the treatment of decompensated hepatitis B cirrhosis,but the former has better renal protection function,which is worthy of further clinical study.