托伐普坦治疗肝硬化低钠血症研究进展

doi:10.3969/j.issn.1672-5069.2018.03.048

摘要/Abstract

摘要： 托伐普坦是一种新型非肽类选择性血管精氨酸加压素V2受体拮抗剂,具有增加肾脏自由水排出、提高血清钠浓度的作用。因失代偿期肝硬化患者自由水排出障碍而常常致低钠血症。应用托伐普坦治疗肝硬化低钠血症可以有效地增加血钠浓度,减少肝性脑病、肝肾综合症、顽固性腹水等并发症的发生。本文简要概述了托伐普坦的作用机制,并介绍了其治疗肝硬化低钠血症的有效性及安全性,以更好地指导临床应用。

关键词: 肝硬化, 低钠血症, 托伐普坦, 精氨酸加压素

Abstract: Tolvaptan is a new type of non-peptide selective arginine vasopressin V2-receptor antagonist,which has the function of increasing renal solute-free water excretion and increasing serum sodium concentration. Due to the disorder of solute-free water excretion,decompensated cirrhotic patients are prone to hyponatremia. Application of tolvaptan in treatment of hyponatremia can effectively increase the concentration of sodium,reduce the risk of complications such as hepatic encephalopathy,hepatorenal syndrome,and refractory ascites. In this paper,we briefly summarized the mechanism of tolvaptan’s effects,the efficacy and safety in treatment of patients with hyponatremia.

Key words: Cirrhosis, Hyponatremia, Tolvaptan, Arginine vasopressin

柏梅综述, 梅浙川审校. 托伐普坦治疗肝硬化低钠血症研究进展[J]. 实用肝脏病杂志, 2018, 21(3): 481-484.

Bai Mei, Mei Zhechuan. Tolvaptan in treatment of cirrhotics with hyponatremia[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(3): 481-484.

参考文献

[1] Ginès P,Guevara M.Hyponatremia in cirrhosis:pathogenesis,clinical significance,and management. Hepatology,2008,48(3):1002-1010.
[2] Sinha VK,Ko B.Hyponatremia in cirrhosis—pathogenesis,treatment,and prognostic significance. Adv Chron Kid Dis,2015,22(5):361-367.
[3] Angeli P,Wong F,Watson H,et al.Hyponatremia in cirrhosis:results of a patient population survey.Hepatology,2006,44(6):1535-1542.
[4] Habib S,Boyer TD.Vasopressin v2-receptor antagonists in patients with cirrhosis,ascites and hyponatremia. Therap Adv Gastroenterol,2012,5(3):189-197.
[5] 向慧玲. 肝硬化低钠血症与Vaptans.世界华人消化杂志,2010,18(12):1244-1249.
[6] Ginès P,Cárdenas A.The management of ascites and hyponatremia in cirrhosis. Semin Liver Dis,2008,28(1):43-58.
[7] Kuiper JJ,de Man RA, van Buuren HR. Review article:management of ascites and associated complications in patients with cirrhosis. Aliment Pharm Ther,2007,26(suppl 2):183-193.
[8] Koealski HJ,Abelmann WH.The cardiac output at rest in Laennec’s cirrhosis. J Clin Invest,1905,32(10):1025-33.
[9] Cornel C,Sieber,Robertoj,et al.Nitric oxide mediates hyporeactivity to vasopressors in mesenteric vessels of portal hypertensive rats.Gastroenterology,1992,103(1):235-239.
[10] Sieber CC,Carloslopez-Talavera J,Groszmann RJ.Role of nitric oxide in the in vitro splanchnic vascular hyporeactivityin ascitic cirrhotic rats.Gsatroenterology,1993,104(6):1750-1754.
[11] Pizcueta P,Pique J,Fernandez M,et al.Modulation of the hyperdynamic circulation of cirrhotic rats by nitric oxide inhibition. Gastroenterology,1992,103(6):1909-1915.
[12] Pizcueta MP,Pique JM,Bosch J,et al.Effects of inhibiting nitric oxide biosynthesis on the systemic and splanchnic circulation of rats with portal hypertension.Br J Pharmacol,1992,105(1):184-190.
[13] Boyer TD.Tolvaptan and hyponatremia in a patient with cirrhosis. Hepatology,2010,51(2):699-702.
[14] Facciorusso A.Role of vaptans in the management of hydroelectrolytic imbalance in liver cirrhosis. World J Hepatol,2014,6(11):793.
[15] Fernández-Esparrach G,Sánchez-Fueyo A,Ginès P,et al.A prognostic model for predicting survival in cirrhosis with ascites. J Hepatol,2001,34(1):46-52.
[16] Biggins SW,Rodriguez HJ,Bacchetti P,et al.Serum sodium predicts mortality in patients listed for liver transplantation. Hepatology,2005,41(1):32-39.
[17] Gaglio P,Marfo K,Chiodo J.Hyponatremia in cirrhosis and end-stage liver disease:treatment with the vasopressin v2-receptor antagonist tolvaptan. Dig Dis Sci,2012,57(11):2774-2785.
[18] Thuluvath PJ, Maheshwari A,Wong F,et al.Oral v2 receptor antagonist(rwj-351647) in patients with cirrhosis and ascites:a randomized,double-blind,placebo-controlled,single ascending do-se study. Aliment Pharmacol Therap,2006,24(6):973-982.
[19] 陈平, 吴云林. 托伐普坦治疗肝硬化腹水合并低钠血症临床研究进展.内科理论与实践,2015,10(4):256-258.
[20] Rangaraian B,Binoy V,Hingmire SS,et al.Tolvaptan.South Asian J Cancer,2014,3(3):182-184.
[21] Zhang X.Clinical efficacy of tolvaptan for treatment of refractory ascites in liver cirrhosis patients. World J Gastroenterol,2014,20(32):11400.
[22] Chung SH,Jun DW,Kim KT,et al.Aquaporin-2 urinary excretion in cirrhosis: relationship to vasopressin and nitric oxide. Dig Dis Sci,2010,55(4):1135-1141.
[23] Nemerovski C,Hutchinson DJ.Treatment of hypervolemic or euvolemic hyponatremia associated with heart failure,cirrhosis,or the syndrome of inappropriate antidiuretic hormone with tolvaptan:a clinical review. Clin Ther,2010,32(6):1015-1032.
[24] Grant P.Cost effectiveness of tolvaptan.BMJ,2011,342:d1947.
[25] Cyr PL,Slawsky KA,Olchanski N,et al.Effect of serum sodium concentration and tolvaptan treatment on length of hospitalization in patients with heart failure. Am J Health Syst Pharm,2011,68(4):328-333.
[26] 阚晓,崔蕾,潘家超,等. 托伐普坦治疗肝硬化失代偿期患者稀释性低钠血症. 中华传染病杂志,2013,31(11):658-662.
[27] Fukui H. Do vasopressin v2 receptor antagonists benefit cirrhotics with refractory ascites World J Gastroenterol,2015,21(41):11584.
[28] Gheorghiade M,Gottlieb SS,Udelson JE,et al.Vasopressin v2 receptor blockade with tolvaptan versus fluid restriction in the treatment of hyponatremia. Am J Cardiol,2006,97(7):1064-1067.
[29] Cárdenas A,Ginès P,Marotta P,et al.Tolvaptan,an oral vasopressin antagonist,in the treatment of hyponatremia in cirrhosis. J Hepatol,2012,56(3):571-578.
[30] Schrier RW,Gross P,Gheorghiade M,et al.Tolvaptan,a selective oral vasopressin v2-receptor antagonist,for hyponatremia. New Engl J Med,2006,355(20):2099-2112.
[31] Yan L,Xie F,Lu J,et al.The treatment of vasopressin v2-receptor antagonists in cirrhosis patients with ascites:a meta-analysis of randomized controlled trials. Bmc Gastroenterol,2015,15(1):1-13.
[32] John S,Thuluvath PJ.Hyponatremia in cirrhosis:pathophysiology and management. World J Gastroenterol,2015,21(11):3197-3205.
[33] European association for the study of the liver. Easl clinical practice guidelines on the management of ascites,spontaneous bacterial peritonitis,and hepatorenal syndrome in cirrhosis. J Hepatol,2010,53(3):397-417.
[34] 郭皓,吴利娟,金哲,等. 血管加压素V2受体拮抗剂托伐普坦治疗肝硬化并低钠血症和肝性水肿的系统评价. 世界华人消化杂志,2016,24(6):938-946.
[35] 张翔云,杜闪闪,祖冬妮,等. 托伐普坦治疗低钠血症疗效及安全性的Meta分析.重庆医科大学学报,2016,41(9):964-970.