Treatment of Refractory Ascites

  • Makoto Segawa
  • Isao SakaidaEmail author


In Japan, the primary therapeutic options for refractory ascites include pharmacotherapy with diuretics, paracentesis with albumin infusion, peritoneovenous shunt using Denver shunt, cell-free and concentrated ascites reinfusion therapy (CART), transjugular intrahepatic portosystemic shunt (TIPS), and liver transplantation.

Recently, the novel diuretic tolvaptan (vasopressin V2 receptor antagonist) has been shown to be effective in the treatment of refractory ascites or hyponatremia in patients with liver cirrhosis. However, a positive effect on the prognosis has not been reported. Patients with diuretic-resistant ascites are often treated by paracentesis with albumin infusion or CART. Although TIPS is effective in controlling refractory ascites, it frequently causes hepatic encephalopathy and requires technical skills to perform. Liver transplantation is the only definitive therapy for refractory ascites; however, it cannot always be performed due to the shortage of donors in Japan.


Tolvaptan Paracentesis Peritoneovenous shunt (Denver shunt) Cell-free and concentrated ascites reinfusion therapy (CART) Transjugular intrahepatic portosystemic shunt (TIPS) 


  1. 1.
    Doggrell SA. Tolvaptan (Otsuka). Curr Opin Investig Drugs. 2004;5(9):977–83.PubMedGoogle Scholar
  2. 2.
    Okita K, Kawazoe S, Hasebe C, et al. Dose-finding trial of tolvaptan in liver cirrhosis patients with hepatic edema: a randomized, double-blind, placebo-controlled trial. Hepatol Res. 2014;44(1):83–91.CrossRefGoogle Scholar
  3. 3.
    Sakaida I, Kawazoe S, Kajimura K, et al. Tolvaptan for improvement of hepatic edema: a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Hepatol Res. 2014;44(1):73–82.CrossRefGoogle Scholar
  4. 4.
    Sakaida I, Nakajima K, Okita K, et al. Can serum albumin level affect the pharmacological action of tolvaptan in patients with liver cirrhosis? A post hoc analysis of previous clinical trials in Japan. J Gastroenterol. 2015;50(10):1047–53.CrossRefGoogle Scholar
  5. 5.
    Sakaida I, Okita K. Correlation between changes in bodyweight and changes in ascites volume in liver cirrhosis patients with hepatic edema in short-term diuretic therapy. Hepatol Res. 2014;44(7):735–9.CrossRefGoogle Scholar
  6. 6.
    Ohki T, Sato K, Yamada T, et al. Efficacy of tolvaptan in patients with refractory ascites in a clinical setting. World J Hepatol. 2015;7(12):1685–93.CrossRefGoogle Scholar
  7. 7.
    Zhang X, Wang SZ, Zheng JF, et al. Clinical efficacy of tolvaptan for treatment of refractory ascites in liver cirrhosis patients. World J Gastroenterol. 2014;20(32):11400–5.CrossRefGoogle Scholar
  8. 8.
    Ginés P, Arroyo V, Quintero E. Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study. Gastroenterology. 1987;93(2):234–41.CrossRefGoogle Scholar
  9. 9.
    Tsien CD, Rabie R, Wong F. Acute kidney injury in decompensated cirrhosis. Gut. 2013;62(1):131–7.CrossRefGoogle Scholar
  10. 10.
    Angeli P, Ginès P, Wong F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol. 2015;62(4):968–74.CrossRefGoogle Scholar
  11. 11.
    Iwamoto T, Maeda M, Hisanaga T, et al. Predictors of the effect of tolvaptan on prognosis of cirrhosis. Intern Med. 2016;55(20):2911–6.Google Scholar
  12. 12.
    Goto A, Terai S, Nakamura M, et al. Re-response to tolvaptan after furosemide dose reduction in a patient with refractory ascites. Clin J Gastroenterol. 2015;8(1):47–51.CrossRefGoogle Scholar
  13. 13.
    Sakaida I. Tolvaptan for the treatment of liver cirrhosis oedema. Expert Rev Gastroenterol Hepatol. 2014;8(5):461–70.CrossRefGoogle Scholar
  14. 14.
    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):571–8.CrossRefGoogle Scholar
  15. 15.
    Dahl E, Gluud LL, Kimer N, et al. Meta-analysis: the safety and efficacy of vaptans (tolvaptan, satavaptan and lixivaptan) in cirrhosis with ascites or hyponatraemia. Aliment Pharmacol Ther. 2012;36(7):619–26.CrossRefGoogle Scholar
  16. 16.
    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.CrossRefGoogle Scholar
  17. 17.
    Runyon BA. AASLD. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012. Hepatology. 2013;57(4):1651–3.CrossRefGoogle Scholar
  18. 18.
    Fukui H, Saito H, Ueno Y, et al. Evidence-based clinical practice guidelines for liver cirrhosis 2015. J Gastroenterol. 2016;51(7):629–50.CrossRefGoogle Scholar
  19. 19.
    Bernardi M, Caraceni P, Navickis RJ, et al. Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials. Hepatology. 2012;55(4):1172–81.CrossRefGoogle Scholar
  20. 20.
    Leveen HH, Christoudias G, Ip M, et al. Peritoneo-venous shunting for ascites. Ann Surg. 1974;180(4):580–91.CrossRefGoogle Scholar
  21. 21.
    Martin LG. Percutaneous placement and management of the Denver shunt for portal hypertensive ascites. AJR Am J Roentgenol. 2012;199(4):W449–53.CrossRefGoogle Scholar
  22. 22.
    Stanley MM, Ochi S, Lee KK, et al. Peritoneovenous shunting as compared with medical treatment in patients with alcoholic cirrhosis and massive ascites. Veterans Administration Cooperative Study on Treatment of Alcoholic Cirrhosis with Ascites. N Engl J Med. 1989;321(24):1632–8.CrossRefGoogle Scholar
  23. 23.
    Ginès P, Arroyo V, Vargas V, et al. Paracentesis with intravenous infusion of albumin as compared with peritoneovenous shunting in cirrhosis with refractory ascites. N Engl J Med. 1991;325(12):829–35.CrossRefGoogle Scholar
  24. 24.
    Rosemurgy AS, Zervos EE, Clark WC, et al. TIPS versus peritoneovenous shunt in the treatment of medically intractable ascites: a prospective randomized trial. Ann Surg. 2004;239(6):883–9; discussion 889–91.CrossRefGoogle Scholar
  25. 25.
    Graziotto A, Rossaro L, Inturri P, et al. Reinfusion of concentrated ascitic fluid versus total paracentesis. A randomized prospective trial. Dig Dis Sci. 1997;42(8):1708–14.CrossRefGoogle Scholar
  26. 26.
    Bernardi M, Rimondi A, Gasbarrini A, et al. Ascites apheresis, concentration and reinfusion for the treatment of massive or refractory ascites in cirrhosis. J Hepatol. 1994;20(2):289–95.CrossRefGoogle Scholar
  27. 27.
    Takamatsu S, Miyazaki H, Katayama K, et al. Current status of CART for refractory ascites. Kan Tan Sui. 2003;46(5):663–9. (in Japanese)Google Scholar
  28. 28.
    Patidar KR, Sydnor M, Sanyal AJ. Transjugular intrahepatic portosystemic shunt. Clin Liver Dis. 2014;18(4):853–76.CrossRefGoogle Scholar
  29. 29.
    Salerno F, Camma C, Enea M, et al. Transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis of individual patient data. Gastroenterology. 2007;133:825–34.CrossRefGoogle Scholar
  30. 30.
    Bai M, Qi XS, Yang ZP, et al. TIPS improves liver transplantation-free survival in cirrhotic patients with refractory ascites: an updated meta-analysis. World J Gastroenterol. 2014;20:2704–14.CrossRefGoogle Scholar
  31. 31.
    Campbell MS, Brensinger CM, Sanyal AJ, et al. Quality of life in refractory ascites: transjugular intrahepatic portal-systemic shunting versus medical therapy. Hepatology. 2005;42:635–40.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Kampo MedicineYamaguchi University HospitalUbeJapan
  2. 2.Department of Gastroenterology and HepatologyYamaguchi University Graduate School of MedicineUbeJapan

Personalised recommendations