盐酸达拉他韦联合阿舒瑞韦对代偿期丙型肝炎肝硬化患者肾功能的影响

Influence of daclatasvir hydrochloride combined with asunaprevir on renal function in patients with compensated hepatitis C cirrhosis

目的观察盐酸达拉他韦抗病毒联合阿舒瑞韦抗病毒治疗对代偿期丙型肝炎肝硬化患者肾功能的影响。方法纳入2017年5月-2017年9月在第四军医大学唐都医院传染科就诊的HCV基因1b型感染所致的代偿期丙型肝炎肝硬化初治患者44例,所有患者均接受盐酸达拉他韦(60 mg,1次/d)联合阿舒瑞韦(100 mg,2次/d)口服抗病毒治疗,疗程24周。比较基线、治疗4周和24周时患者HCV RNA阴转率、ALT复常率、尿素氮、肌酐和估算肾小球滤过率(eGFR)的变化。其中eGFR分别采用简化的肾脏病饮食改良(MDRD)和慢性肾脏病流行病学合作研究(CKD-EPI)两种方法进行计算。对于符合正态分布的计量资料组间比较采用方差分析,进一步两两比较采用SNK-q检验。结果治疗24周时患者的HCV RNA阴转率和ALT复常率分别为100%(44/44)和97.50%(39/40)。治疗过程中,患者尿素氮水平在24周[(4.91±1.41)mmol/L]较基线[(4.43±1.09)mmol/L]显著升高,差异具有统计学意义(q=2.322,P=0.025)。但患者肌酐水平在治疗4周和24周时与基线比较差异均无统计学意义(P值均>0.05),同时,无论MDRD法还是CKD-EPI法计算的eGFR水平在治疗4周和24周时与基线比较差异亦均无统计学意义(P值均>0.05)。但在采用MDRD法计算的基线eGFR水平<90 ml·min^(-1)·1.73m^(-2)的14例患者中,治疗24周时eGFR水平[(89.65±15.85)ml·min^(-1)·1.73 m^(-2)]较此14例患者的基线水平[(82.81±7.16)ml·min^(-1)·1.73 m^(-2)]明显升高,差异具有统计学意义(q=2.303,P=0.038)。结论盐酸达拉他韦联合阿舒瑞韦对代偿期丙型肝炎肝硬化患者肾功能无明显影响,有待扩大样本进一步研究。

Objective To investigate the influence of daclatasvir hydrochloride combined with asunaprevir on renal function in patients with compensated hepatitis C cirrhosis. Methods A total of 44 previously untreated patients with compensated hepatitis C cirrhosis caused by hepatitis C virus genotype 1 b infection who visited Department of Infectious Diseases in Tangdu Hospital,Fourth Military Medical University,from May 2017 to September 2017 were enrolled. All patients were given oral daclatasvir hydrochloride（ 60 mg,once a day） combined with asunaprevir（ 100 mg,twice a day） as the antiviral therapy,and the course of treatment was 24 weeks. The changes in HCV RNA clearance rate,alanine aminotransferase（ ALT） normalization rate,blood urea nitrogen,creatinine,and estimated glomerular filtration rate（ eGFR）were measured from baseline to weeks 4 and 24 of treatment were observed,and eGFR was calculated using the Modification of Diet In Renal Disease（ MDRD） and Chronic Kidney Disease Epidemiology Collaboration（ CKD-EPI） equations. The chi-squared test was used for comparison of normally distributed continuous data between groups,and the SNK-q test was used for further comparison between two groups. Results At week 24 of treatment,the HCV RNA clearance rate was 100%（ 44/44） and the ALT normalization was 97. 50%（ 39/40）. There was a significant increase in blood urea nitrogen from baseline（ 4. 43 ± 1. 09 mmol/L） to week 24 of treatment（ 4. 91 ± 1. 41 mmol/L）（ q = 2. 322,P = 0. 025）,while there was no significant change in creatinine from baseline to week 4 or 24 of treatment（ both P〈0. 05）. There was no significant change in eGFR calculated using either MDRD or CKD-EPI equation from baseline to week 4 or 24 of treatment（ both P〈0. 05）. As for the 14 patients with a baseline eGFR of 90 ml/min/1. 73 m^2 calculated using the MDRD equation,they had a significant increase in eGFR from baseline（ 82. 81 ± 7. 16 ml/min/1. 73 m^2） to week 24 of treatment（ 89. 65 ± 15. 85 ml/min/1. 73 m^2）（ q = 2. 303,P = 0. 038）. Conclusion Daclatasvir hydrochloride combined with asunaprevir has no significant influence on renal function in patients with compensated hepatitis C cirrhosis,and there is a need for more studies with a large sample size.