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长期恩替卡韦治疗对慢性乙型肝炎患者肾功能的影响
Influence of long-term entecavir treatment on renal function in patients with chronic hepatitis B
文章发布日期:2020年06月08日  来源:  作者:张青,张飙,王培,等  点击次数:356次  下载次数:50次

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【摘要】:目的 探讨长期应用ETV抗病毒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2015年1月-2019年6月在淮安市第四人民医院接受ETV抗病毒治疗半年以上的CHB患者232例。按不同性别、年龄(<或≥65岁)、有无肝硬化和肾小球滤过率(eGFR)(<或≥90 ml·min-1·1.73 m-2)分组,探讨各个亚组的ETV治疗前后的肾功能指标[血尿素氮(BUN)、血肌酐(Scr)和eGFR]变化情况。并比较ETV抗病毒方案在抗病毒前后总体ALT、AST、Alb、HBsAg、HBV DNA和肾功能指标(BUN、Scr和eGFR)变化。采用全自动生化分析仪检测血生化指标,包括ALT、AST、Alb、BUN、Scr和eGFR,采用实时荧光定量PCR 法检测HBV DNA,采用罗氏电化学发光法检测血清HBsAg定量。正态分布的计量资料组间比较采用配对t检验,非正态分布的计量资料组间比较采用Wilcoxon秩和检验,采用二分类logistic回归分析筛选ETV抗病毒治疗后eGFR<90 ml·min-1·1.73 m-2的危险因素。结果 经半年以上ETV抗病毒治疗,患者ALT、AST、HBsAg和HBV DNA均下降(Z值分别为-9.496、-9.577,t值分别为5.013、20.777,P值均<0.05),Alb升高(t=-10.832,P<0.05);与基线比较,BUN和Scr升高(t值分别为-2.685、-2.376,P值均<0.05),eGFR下降(t=3.207,P<0.05);进一步对各个亚组进行分析的结果显示,eGFR≥90 ml·min-1·1.73 m-2、非老年、肝硬化和男性组BUN升高(t值分别为-3.403、-3.187、-2.267、-2.187,P值均<0.05),且Scr升高(t值分别为-3.716、-3.614、-2.291、-2.115,P值均<0.05),eGFR下降(t值分别为4.846、4.152、2.458、2.946,P值均<0.05),非肝硬化组eGFR降低(t=2.163,P<0.05),但BUN和Scr变化无统计学意义(P>0.05)。二分类logistic回归分析显示,随着葡萄糖水平的升高(OR=1.296, 95%CI: 1.052~1.597, P=0.015)和TC水平的下降(OR=0.436, 95%CI: 0.286~0.664, P<0.001),ETV治疗后eGFR<90 ml·min-1·1.73 m-2的风险升高。结论 ETV 抗病毒治疗可有效降低患者ALT、AST、HBsAg、HBV DNA,升高Alb,但可致eGFR≥90 ml·min-1·1.73 m-2、非老年和肝硬化患者BUN和Scr升高,eGFR下降,血葡萄糖和TC是ETV治疗后eGFR<90 ml·min-1·1.73 m-2的影响因素。
【Abstract】:Objective To investigate the influence of long-term entecavir (ETV) antiviral therapy on renal function in patients with chronic hepatitis B (CHB). Methods A retrospective analysis was performed for the clinical data of 232 CHB patients who received ETV antiviral therapy for more than half a year in Huai’an Fourth People’s Hospital from January 2015 to June 2019. The patients were divided into groups according to sex, age (<65 years or ≥65 years), presence or absence of liver cirrhosis, and estimated glomerular filtration rate (eGFR) (<90 ml/min/1.73 m2 or ≥90 ml/min/1.73 m2), and the changes in renal function markers [blood urea nitrogen (BUN), serum creatinine (SCr), and eGFR] after treatment were observed for each group. The changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), HBsAg, HBV DNA, and renal function markers (BUN, SCr, and eGFR) after ETV antiviral therapy were also observed. An automatic biochemical analyzer was used to measure biochemical parameters including ALT, AST, Alb, BUN, SCr, and eGFR; RT-qPCR was used to measure HBV DNA; Roche electrochemical luminescence was used to measure serum HBsAg quantification. The paired t-test was used for comparison of normally distributed continuous data between groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups; a binary logistic regression analysis was used to identify the risk factors for eGFR <90 ml/min/1.73 m2 after ETV antiviral therapy. Results After ETV antiviral therapy for more than half a year, there were significant reductions in ALT, AST, HBsAg, and HBV DNA (Z=-9.496 and -9.577, t=5.013 and 20.777, all P<0.05) and a significant increase in Alb (t=-10.832, P<0.05); compared with baseline, there were significant increases in BUN and SCr (t=-2.685 and -2.376, both P<0.05) and a significant reduction in eGFR (t=3.207, P<0.05). Further analysis of each subgroup showed that the eGFR ≥90 ml/min/1.73 m2 group, the non-elderly group, the liver cirrhosis group, and the male group had significant increases in BUN (t=-3.403, -3.187, -2.267, and -2.187, all P<0.05) and SCr (t=-3.716, -3.614, -2.291, and -2.115, all P<0.05) and a significant reduction in eGFR (t=4.846, 4.152, 2.458, and 2.946, all P<0.05), and the non-liver cirrhosis group had a significant reduction in eGFR (t=2.163, P<0.05) and had no significant changes in BUN and SCr (P>0.05). The binary logistic regression analysis showed that with the increase in glucose level (odds ratio [OR]=1.296, 95% confidence interval [Cl]: 1.052-1.597, P=0.015) and the reduction in total cholesterol (TC) (OR=0.436, 95% Cl: 0.286-0.664, P<0.001), the risk of eGFR <90 ml/min/1.73 m2 increased after ETV therapy. Conclusion ETV antiviral therapy can effectively reduce ALT, AST, HBsAg, and HBV DNA and increase Alb, but it can cause the increases in BUN and SCr and the reduction in eGFR in patients with eGFR >90 ml/min/1.73 m2, non-elderly patients, and patients with liver cirrhosis. Blood glucose and TC are influencing factors for eGFR <90 ml/min/1.73 m2 after ETV therapy.
【关键字】:乙型肝炎,慢性; 治疗学; 恩替卡韦; 肾功能不全
【Key words】:hepatitis B,Chronic; therapeutics; entecavir; renal insufficiency
【引证本文】:ZHANG Q, ZHANG B, WANG P, et al. Influence of long-term entecavir treatment on renal function in patients with chronic hepatitis B[J]. J Clin Hepatol, 2020, 36(7): 1491-1495. (in Chinese)
张青, 张飙, 王培, 等. 长期恩替卡韦治疗对慢性乙型肝炎患者肾功能的影响[J]. 临床肝胆病杂志, 2020, 36(7): 1491-1495.

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