核苷和核苷酸类药物对慢性乙型肝炎患者肾小球滤过率和血肌酐水平的影响

Effects of nucleos(t) ide analogues on estimated glomerular filtration rate and serum creatinine level in patients with chronic hepatitis B

目的研究核苷和核苷酸类药物(NAs)对慢性乙型肝炎(CHB)患者肾小球滤过率(e GFR)和血肌酐(Scr)的影响。方法收集2010年9月-2014年9月在大连医科大学附属第二医院感染科门诊及住院的CHB患者184例,根据应用NAs的不同将其分为3组,分别为阿德福韦酯(ADV)组(n=58)、替比夫定(LDT)组(n=62)和恩替卡韦(ETV)组(n=64),疗程均为104周。比较治疗前后各组e GFR、Scr水平的变化。计量资料组内治疗前后比较采用Wilcoxon秩和检验,多组间比较采用Kruskal-Wallis H秩和检验,计数资料组间比较采用χ2检验。结果 ETV组治疗52、104周后Scr、e GFR变化均不明显,与基线相比差异无统计学意义(P值均>0.05);与基线水平相比,ADV组治疗52、104周的Scr水平升高,e GFR水平降低,差异均有统计学意义(Z值分别为-3.020、-3.456、-4.623、-4.831,P值分别为0.018、0.008、0.004、<0.001);LDT组治疗52、104周的Scr水平较基线降低,e GFR较基线升高,差异均有统计学意义(Z值分别为-5.596、-5.687、-5.335、-5.162,P值分别为0.007、0.003、0.002、<0.001)。治疗104周后ADV组与LDT组e GFR水平的分布比较差异有统计学意义(χ2=21.039,P<0.001),其中LDT组中有77.78%(7/9)的患者e GFR水平转为≥90 ml·min-1·1.73 m-2,ADV组中有23.81%(10/42)的患者e GFR水平转为<90 ml·min-1·1.73 m-2。结论在治疗过程中观察到LDT治疗能提高e GFR,显著改善肾功能,而ADV治疗会导致e GFR降低,有潜在的肾毒性,且在NAs治疗CHB患者过程中e GFR比Scr更能早期反映出肾损伤。有关LDT提高e GFR保护肾功能的作用机制有待进一步研究。

Objective To investigate the effects of nucleos（t） ide analogues （NAs） on the estimated glomerular filtration rate （eGFR） and serum creatinine （Scr） in patients with chronic hepatitis B （CHB）. Methods A total of 184 patients with CHB who visited and were hos- pitalized in the Second Affiliated Hospital of Dalian Medical University from September 2010 to September 2014 were enrolled and divided into adefovir （ADV） group （58 patients） telbivudine （LDT） group （62 patients）, and entecavir （ETV） group （64 patients）, according to the NAs administered. The course of treatment was 104 weeks for all groups. The changes in eGFR and Scr level in each group after treat- ment were evaluated. The cbi - square test was applied for comparison of categorical data between groups ; the Wilcoxon rank sum test was applied for comparison of continuous data before and after treatment within one group, and Kruskal - Wallis H rank sum test was applied for comparison between groups. Results In the ETV group, there were no significant changes in Scr and eGFR after 52 and 104 weeks of treat- ment （ all P 〉0.05） ; in the ADV group, there was a significant increase in Scr level and a significant reduction in eGFR after 52 and 104 weeks of treatment （Z = - 3. 020, - 3. 456, - 4. 623, and - 4. 831, P = 0. 018, 0. 008, 0. 004, and 〈 0. 001, respectively） ; in the LDT group, there was a significant reduction in Scr level and a significant increase in eGFR after 52 and 104 weeks of treatment （Z = - 5. 596, - 5. 687, - 5. 335, and - 5. 162, P = 0.007, 0.003,0. 002, and 〈 0. 001, respectively）. After 104 weeks of treatment, the dis- tribution of eGFR showed a significant difference between the ADV group and the LDT group （X2 =21. 039, P 〈0. 001 ） ; in the LDT group, 77.78% （7/9） of all the patients achieved eGFR 〉190 ml· min-1 · 1.73 m-2, and in the ADV group, 23.81% （10/42） of all the patients achieved eGFR 〈90 ml · min- 1· 1.73 m-2. Conclusion During the treatment, LDT can increase eGFR and improve renal function significantly,while ADV may reduce eGFR, with potential nephrotoxicity. During the treatment for patients with CHB, eGFR may reflect renal injury much earlier than Scr. The mechanisms of action of LDT in increasing eGFR and protecting renal function await further investigation.