聚乙二醇干扰素α-2a与替比夫定对慢性乙型肝炎患者肾功能影响的比较

Influence of pegylated interferonα- 2a versus telbivudine on renal function in patients with chronic hepatitis B

目的观察聚乙二醇干扰素(PEG-IFN)α^(-2)a与替比夫定(Ld T)治疗对慢性乙型肝炎(CHB)患者肾功能的影响。方法回顾性分析2007年7月^(-2)013年3月于第四军医大学唐都医院进行Ⅳ期临床试验的初治HBe Ag阳性CHB患者临床资料,共纳入患者92例,其中39例皮下注射PEG-IFNα^(-2)a(PEG-IFNα^(-2)a组),180μg/周;53例接受Ld T抗病毒治疗(Ld T组),600 mg/d。比较基线、治疗24周和48周时患者HBV DNA阴转率、ALT复常率、血清肌酐、尿素氮和估算肾小球滤过率(e GFR)的变化,其中e GFR分别采用慢性肾病流行病学合作研究(CKD-EPI)和简化的肾病饮食改良(MDRD)2种方法进行计算。对于符合正态分布的计量资料2组间比较采用独立样本t检验,不符合正态分布的计量资料2组间比较采用Wilcoxon秩和检验,组内治疗前后比较采用重复测量数据的方差分析,在进行重复测量数据方差分析前对资料进行Mauchly球形检验;计数资料组间比较采用χ~2检验。结果治疗过程中,PEG-IFNα^(-2)a组血清肌酐水平在24周[(0.68±0.11)mg/dl]和48周[(0.67±0.11)mg/dl]均较基线明显降低[(0.75±0.11)mg/dl],差异均有统计学意义(P值均<0.000 1),e GFR水平在24周[(128.30±10.98)ml·min^(-1)·1.73m^(-2)(CKD-EPI法)/(143.9±25.82)ml·min^(-1)·1.73m^(-2)(MDRD法)]和48周[(128.00±10.17)ml·min^(-1)·1.73m^(-2)(CKD-EPI法)/(144.30±24.68)ml·min^(-1)·1.73 m^(-2)(MDRD法)]均较基线水平[(123.10±9.64)ml·min^(-1)·1.73 m^(-2)(CKD-EPI法)/(127.40±20.16)ml·min^(-1)·1.73 m^(-2)(MDRD法)]明显升高,差异均有统计学意义(P值均<0.000 1)。Ld T组患者治疗24周时血清肌酐[(0.73±0.13)mg/dl]及e GFR水平[(122.30±11.22)ml·min^(-1)·1.73 m^(-2)(CKD-EPI法)/(128.10±20.67)ml·min^(-1)·1.73 m^(-2)(MDRD法)]与基线水平[血清肌酐:(0.74±0.13)mg/dl;e GFR:(121.50±11.21)ml·min^(-1)·1.73 m^(-2)(CKDEPI法)/(126.40±20.96)ml·min^(-1)·1.73 m^(-2)(MDRD法)]比较差异均无统计学意义(P值均>0.05),48周时血清肌酐(0.68±0.12 mg/dl)较基线明显降低,e GFR[(125.30±11.55)ml·min^(-1)·1.73 m^(-2)(CKD-EPI法)/(138.0±25.94)ml·min^(-1)·1.73 m^(-2)(MDRD法)]较基线明显升高,差异均有统计学意义(P值均<0.000 1)。治疗48周时,Ld T组的HBV DNA阴转率和ALT复常率均高于PEG-IFNα^(-2)a组(HBV DNA阴转率:60.4%vs 38.5%;ALT复常率:75.5%vs 33.3%),差异均有统计学意义(χ~2值分别为6.17、16.34,P值分别为0.037、<0.000 1)。结论 PEG-IFNα^(-2)a和Ld T对CHB患者肾功能均无明显影响。

Objective To investigate the influence of pegylated interferonα- 2a（ PEG- IFNα- 2a） versus telbivudine（ Ld T） on renal function in patients with chronic hepatitis B（ CHB）. Methods The clinical data of 92 previously untreated HBe Ag- positive CHB patients who participated in the CHB IV clinical trial in Tangdu Hospital of Fourth Military Medical University from July 2007 to March 2013 were analyzed retrospectively,and among these patients,39 received subcutaneous injection of PEG- IFNα- 2a 180 μg / week（ PEG- IFNα- 2a group） and 53 received antiviral therapy with Ld T 600 mg / d（ Ld T group）. The HBV DNA clearance rate,alanine aminotransferase（ ALT）normalization rate,serum creatinine,urea nitrogen,and estimated glomerular filtration rate（ e GFR） at baseline and weeks 24 and 48 of treatment were calculated and analyzed,and e GFR was calculated by Chronic Kidney Disease Epidemiology Collaboration（ CKD- EPI） or Modification of Diet in Renal Disease（ MDRD）. The independent samples t- test was used for comparison of normally distributed continuous data between the two groups,and the Wilcoxon rank sum test was used for comparison of continuous data with non- normal distribution between the two groups; the repeated measures analysis of variance was used for comparison of data before and after treatment within one group,and Mauchly＇s test of sphericity was performed for data before the repeated measures analysis of variance; the chi- square test was used for comparison of categorical data between the two groups. Results In the PEG- IFNα- 2a group,serum creatinine decreased significantly at weeks 24 and 48 of treatment compared with the baseline value（ 0. 68 ± 0. 11 mg / dl and 0. 67 ± 0. 11 mg / dl vs 0. 75 ± 0. 11 mg / dl,P〈0. 000 1）,and e GFR increased significantly at week 24 [128. 30 ± 10. 98 ml / min /1. 73 m2（ CKD- EPI） or 143. 90 ± 25. 82 ml/min/1. 73m2（ MDRD） ]and week 48 [128. 00 ± 10. 17 ml/min/1. 73 m2（ CKD- EPI） or 144. 30 ± 24. 68 ml/min/1. 73 m2（ MDRD） ] compared with the baseline value [123. 10 ± 9. 64 ml / min /1. 73 m2（ CKD- EPI） or 127. 40 ± 20. 16 ml/min/1. 73 m2（ MDRD） ]（ P〈0. 000 1）. In the Ld T group,serum creatinine（ 0. 73 ± 0. 13 mg / dl） and e GFR [122. 30 ± 11. 22 ml / min /1. 73 m2（ CKD- EPI） or 128. 10 ± 20. 67 ml/min /1. 73 m2（ MDRD） ]at week 24 showed significant differences from those at baseline [serum creatinine： 0. 74 ± 0. 13 mg/dl; e GFR：121. 50 ± 11. 21 ml / min /1. 73 m2（ CKD- EPI） or 126. 40 ± 20. 96 ml/min/1. 73 m2（ MDRD） ]（ P〈0. 05）; compared with the baseline values,serum creatinine at week 48（ 0. 68 ± 0. 12 mg / dl） decreased significantly（ P〈0. 000 1）,while e GFR [125. 30 ± 11. 55 ml / min /1. 73 m2（ CKD- EPI） or 138. 00 ± 25. 94 ml/min/1. 73 m2（ MDRD） ]increased significantly（ P〈0. 000 1）. At week 48 of treatment,the Ld T group had significantly higher HBV DNA clearance rate and ALT normalization rate than the PEG- IFNα- 2a group（ HBV DNA seroconversion rate： 60. 4% vs 38. 5%,χ-2= 6. 17,P = 0. 037; ALT normalization rate： 75. 5% vs 33. 3%; χ-2= 16. 34,P〈0. 000 1）. Conclusion PEG- IFNα- 2a and Ld T do not influence renal function in CHB patients.