长期应用核苷（酸）类药物治疗对慢乙肝患者肾功能的影响

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (9): 1029-1034.

长期应用核苷（酸）类药物治疗对慢乙肝患者肾功能的影响

霍娜，陆海英，王贵强，黄明杰，吴赤红，蔺小红

北京大学第一医院感染疾病科，北京 100034

收稿日期:2016-09-27 修回日期:2016-11-11 出版日期:2017-09-26 发布日期:2017-09-30
通讯作者: 陆海英，女，主任医师，副教授，主要从事病毒性肝炎的研究。 E-mail：luhaiying00@126.com
作者简介:霍娜，女，博士研究生，主要从事病毒性肝炎的研究。
基金资助:
国家十二五科技重大专项资助项目（2012ZX10002003）

Effects of nucleos(t)ide analogues on renal function in patients with chronic hepatitis B

HUO Na, LU Haiying, WANG Guiqiang, HUANG Mingjie, WU Chihong, LIN Xiaohong

Department of Infectious Disease, Peking University First Hospital, Beijing 100034, China

Received:2016-09-27 Revised:2016-11-11 Online:2017-09-26 Published:2017-09-30

摘要/Abstract

摘要：

目的: 总结长期应用核苷（酸）类药物抗病毒治疗对肾脏功能的影响。方法: 记录176例长期应用核苷（酸）类药物抗病毒治疗的慢乙肝患者［阿德福韦酯(ADV)+ 拉米夫定(LAM)治疗组28例，阿德福韦酯(ADV)+ 恩替卡韦(ETV)组20例，LAM组21例，ADV组26例，ETV组81例］的临床资料，并计算eGFR。采用Kruskal-Wallis检验、MannWhitney检验、χ2检验进行差异性比较分析。结果: ADV+LAM治疗组、ADV+ETV组、LAM组、ADV组、ETV组患者的eGFR分别为:(78.9±13.8)、（80.2±15.8）、（78.8±12.9）、（74.6±14.6）、（79.5±13.1） mL·min-1·1.73 m-2，P>0.05；eGFR<80 mL·min-1·1.73 m-2的病例数分别为14(50%)、12(60%)、10(47.6%)、20(69.2%)、47（58.0%），P>0.05；血清磷水平分别为（0.95±0.14）、（0.92±0.11）、（1.02±0.13）、（0.92±0.16）、（0.97±0.14） mmol/L；血清磷降低的病例数分别为15(53.6%)、13（65%）、6（28.6%）、13（50%）、39（48.1%），而且LAM组与ADV+ETV组相比，χ2 = 5.466 9，P=0.019 4。结论: 长期核苷（酸）类药物抗病毒治疗可影响肾脏功能，其中ADV的影响最明显，ETV次之，LAM最轻，而且监测eGFR和血清磷水平能更敏感地反映肾脏受损情况。

关键词: 肾小球滤过率估算值（eGFR）, 肾损害, 拉米夫定, 阿德福韦酯, 恩替卡韦

Abstract:

AIM: To summarize the effects of nucleoside (acid) drugs on renal function in accepting antiviral therapy chronic hepatitis B patients. METHODS: Clinical data of 176 cases of chronic hepatitis B patients treated with nucleoside (acid) antiviral therapy (28 cases in ADV+LAM treatment group, 20 cases in ADV+ETV group, 21 cases in LAM group, 26 cases in ADV group, 81 cases in group ETV) were recorded, estimated glomerular filtration rate (eGFR) was calculated. The Kruskal-Wallis test or Mann-Whitney test or chi square difference test were used for comparative analysis of differences.RESULTS:The eGFR of the patients in ADV+LAM treatment group, ADV+ETV group, LAM group, ADV group and ETV group were (78.9±13.8),（80.2±15.8）,（78.8±12.9）,（74.6±14.6）,（79.5±13.1） mL·min-1·1.73 m-2, respectively, P>0.05; the number of cases with eGFR less than 80 mL·min-1·1.73 m-2 were 14(50%), 12(60%), 10(47.6%), 20(69.2%), 47（58.0%）, respectively, P＞0.05. Serum phosphorus levels were （0.95±0.14）,（0.92±0.11）,（1.02±0.13）,（0.92±0.16）,（0.97±0.14）mmol/L, respectively, P>0.05； the number of cases with a decreased serum phosphorus level were 15(53.6%), 13（65%）, 6（28.6%）, 13（50%）, 39（48.1%）, respectively; Furthermore, there were statistically significant differences between LAM group and ADV+ETV group (χ2=5.466 9, P=0.019 4). CONCLUSION: Long-term antiviral therapy of nucleoside (acid) drugs may affect renal function, in which the effect of ADV is the most obvious, ETV is the second, and LAM is the mildest. The monitoring of eGFR and serum phosphorus level is more sensitive to reveal the damage of kidney.

Key words: estimated glomerular filtration rate, renal damage, lamivudine, adefovir, entecavir

中图分类号:

R749

霍娜，陆海英，王贵强，黄明杰，吴赤红，蔺小红. 长期应用核苷（酸）类药物治疗对慢乙肝患者肾功能的影响[J]. 中国临床药理学与治疗学, 2017, 22(9): 1029-1034.

HUO Na, LU Haiying, WANG Guiqiang, HUANG Mingjie, WU Chihong, LIN Xiaohong. Effects of nucleos(t)ide analogues on renal function in patients with chronic hepatitis B[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(9): 1029-1034.

参考文献

［1］Lai CL, Chien RN, Leung NW, et al. A one-year trial of lamivudine for chronic hepatitis B［J］. N Engl J Med, 1998,339(2):61-68.
［2］Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Long-term therapy with adefovirdipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years［J］. Gastroenterology, 2006,131(6):1743-1751.
［3］Lai CL, Gane E, Liaw YF, et al. Telbivudine versus lamivudine in patients with chronichepatitis B［J］. N Engl J Med, 2007, 357(25):2576-2588.
［4］Lai CL, Shouval D, Lok AS, et al. Entecavir versus lamivudine for patients withHBeAg-negative chronic hepatitis B［J］. N Engl J Med, 2006, 354(10):1011-1020.
［5］中华医学会肝病分会中华医学感染病学分会.慢性乙型肝炎防治指南［J］. 中国肝病学杂志, 2011, 19（1）：13-33.
［6］苏超，张桂霞，王瑞峰，等. CKD-EPI方程估算中国慢性肾脏病患者肾小球滤过率的适用性评价［J］.中华疾病控制杂志, 2013, 17(7):621-624.
［7］Perrillo R, Hann HW, Mutimer D, et al. Adefovirdipivoxil added to ongoing lamivudine inchronic hepatitis B with YMDD mutant hepatitis B virus［J］.Gastroenterology, 2004,126(1):81-90.
［8］Shimohata H,Sakai S,Ogawa Y, et al. Osteomalacia due to Fanconi's syndrome and renal failure caused by long-term low-doseadefovir dipivoxil［J］.Clin Exp Nephrol, 2013,17(1):147-148.
［9］Tanaka M, Setoguchi T, Ishidou Y, et al. Pathological femoral fractures due to osteomalacia associated withadefovir dipivoxiltreatment for hepatitis B: a case report［J］.Diagn Pathol, 2012，7:108.
［10］Li L, Dong GF, Zhang X, et al. Adefovir dipivoxil-induced Fanconi syndrome and hypophosphatemic osteomalacia associated with muscular weakness in a patient withchronic hepatitis B［J］.Nan Fang Yi Ke Da Xue Xue Bao,2011,31(11):1956.
［11］Sun XF, Zhang HB, Li XP, et al. A case ofadefovirdipivoxilinduced hypophosphataemicosteomalacia and literature review［J］. Zhonghua Nei Ke Za Zhi, 2011, 50(9):754-757.
［12］Gara N,Zhao X,Collins MT, et al. Renal tubular dysfunction during long-term adefovir or tenofovir therapy inchronic hepatitis B［J］.Aliment Pharmacol Ther, 2012, 35(11):1317-1325.
［13］Qi X,Wang JY,Mao RC, et al. Impact of nucleos(t)ide analogues on the estimated glomerular filtration rate in patients withchronic hepatitis B: a prospective cohort study in China［J］.J Viral Hepat,2015,22(1):46-54.
［14］Amarapurkar DN,Patel N.Increased eGFR withtelbivudinein combination therapy ofchronic hepatitis Binfection［J］.Indian J Gastroenterol,2014,33(1):89-91.
［15］Qi X,Wang J,Chen L, et al. Impact of nucleos(t)ide analogue combination therapy on the estimated glomerular filtration rate in patients with chronic hepatitis B［J］.Medicine (Baltimore),2015,94(15):e646.
［16］Wang X,Zhang C,Zhu Y, et al. Efficacy of 2years ofentecavirplus adefovir therapy in patients withchronic hepatitis Bwho had failed on prior nucleos(t)ide analog treatment［J］.Antiviral Res, 2014, 103:71-77.

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