Early Administration of Tolvaptan Can Improve Survival in Patients with Cirrhotic Ascites

Overview

Journal J Clin Med

Specialty General Medicine

Date 2021 Jan 20

PMID 33466878

Citations 2

Authors

Atsushi Hosui

Takafumi Tanimoto

Toru Okahara

Munehiro Ashida

Kohsaku Ohnishi

Yuhhei Wakahara

Yukihiro Kusumoto

Toshio Yamaguchi

Yuka Sueyoshi

Motohiro Hirao

Takuya Yamada

Naoki Hiramatsu

Affiliations

Soon will be listed here.

Abstract

(1) Backgrounds and aim: Tolvaptan, a selective vasopressin type 2 receptor antagonist, was approved for ascites, and its short-term efficacy and safety have been confirmed. However, it is still unclear whether this novel drug may improve long-term survival rates in cirrhotic patients with ascites. (2) Patients and methods: A total of 206 patients who responded insufficiently to conventional diuretics and were hospitalized for refractory ascites for the first time were retrospectively enrolled in this study. Among them, the first 57 consecutive patients were treated with conventional diuretics (the conventional therapy group); the latter 149 consecutive patients were treated with tolvaptan in addition to the conventional therapy (the tolvaptan group). (3) Results: The exacerbation of renal function was significantly milder in the tolvaptan group than in the conventional therapy group. The prognostic factors for survival in the tolvaptan group were being male, having hyperbilirubinemia, having a high blood urea nitrogen (BUN), and receiving high-dose furosemide at the start of tolvaptan treatment. The one-year and three-year cumulative survival rates were 67.8 and 45.3%, respectively, in patients with low-dose furosemide (<40 mg/day) at the start of tolvaptan treatment. The prognosis was significantly better in the tolvaptan group with low-dose furosemide than in the conventional therapy group ( < 0.001). (4) Conclusion: Tolvaptan can improve survival in patients with cirrhotic ascites, especially when tolvaptan is started before high-dose furosemide administration.

Citing Articles

Special Issue "New Therapies of Liver Diseases".

Toniutto P J Clin Med. 2022; 11(7).

PMID: 35407406 PMC: 8999668. DOI: 10.3390/jcm11071798.

Management of Ascites in Patients with Cirrhosis: An Update.

Zaccherini G, Tufoni M, Iannone G, Caraceni P J Clin Med. 2021; 10(22).

PMID: 34830508 PMC: 8621554. DOI: 10.3390/jcm10225226.

References

Schuppan D, Afdhal N . Liver cirrhosis. Lancet. 2008; 371(9615):838-51. PMC: 2271178. DOI: 10.1016/S0140-6736(08)60383-9. View

Planas R, Montoliu S, Belen Balleste , Rivera M, Miquel M, Masnou H . Natural history of patients hospitalized for management of cirrhotic ascites. Clin Gastroenterol Hepatol. 2006; 4(11):1385-94. DOI: 10.1016/j.cgh.2006.08.007. View

Atsukawa M, Tsubota A, Kato K, Abe H, Shimada N, Asano T . Analysis of factors predicting the response to tolvaptan in patients with liver cirrhosis and hepatic edema. J Gastroenterol Hepatol. 2017; 33(6):1256-1263. DOI: 10.1111/jgh.14047. View

Uchida Y, Inao M, Tsuji S, Uemura H, Kouyama J, Naiki K . Furosemide as a factor to deteriorate therapeutic efficacy of tolvaptan in patients with decompensated cirrhosis. Hepatol Res. 2020; 50(12):1355-1364. DOI: 10.1111/hepr.13566. View

Runyon B . 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. DOI: 10.1002/hep.26359. View

Hiramine Y, Uojima H, Nakanishi H, Hiramatsu A, Iwamoto T, Kimura M . Response criteria of tolvaptan for the treatment of hepatic edema. J Gastroenterol. 2017; 53(2):258-268. DOI: 10.1007/s00535-017-1366-6. View

Jaber B, Almarzouqi L, Borgi L, Seabra V, Balk E, Madias N . Short-term efficacy and safety of vasopressin receptor antagonists for treatment of hyponatremia. Am J Med. 2011; 124(10):977.e1-9. PMC: 3187567. DOI: 10.1016/j.amjmed.2011.04.028. View

Gines P, Cardenas A, Arroyo V, Rodes J . Management of cirrhosis and ascites. N Engl J Med. 2004; 350(16):1646-54. DOI: 10.1056/NEJMra035021. View

Sakaida I, Kawazoe S, Kajimura K, Saito T, Okuse C, Takaguchi K . Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Hepatol Res. 2013; 44(1):73-82. DOI: 10.1111/hepr.12098. View

10.

Londono M, Cardenas A, Guevara M, Quinto L, De Las Heras D, Navasa M . MELD score and serum sodium in the prediction of survival of patients with cirrhosis awaiting liver transplantation. Gut. 2007; 56(9):1283-90. PMC: 1954951. DOI: 10.1136/gut.2006.102764. View

11.

Kawaratani H, Fukui H, Moriya K, Noguchi R, Namisaki T, Uejima M . Predictive parameter of tolvaptan effectiveness in cirrhotic ascites. Hepatol Res. 2016; 47(9):854-861. DOI: 10.1111/hepr.12826. View

12.

Fukui H . Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia. World J Hepatol. 2015; 7(3):425-42. PMC: 4381167. DOI: 10.4254/wjh.v7.i3.425. View

13.

Salerno F, Guevara M, Bernardi M, Moreau R, Wong F, Angeli P . Refractory ascites: pathogenesis, definition and therapy of a severe complication in patients with cirrhosis. Liver Int. 2010; 30(7):937-47. DOI: 10.1111/j.1478-3231.2010.02272.x. View

14.

Kogiso T, Sagawa T, Kodama K, Taniai M, Tokushige K . Impact of continued administration of tolvaptan on cirrhotic patients with ascites. BMC Pharmacol Toxicol. 2018; 19(1):87. PMC: 6299627. DOI: 10.1186/s40360-018-0277-3. View

15.

Schrier R, Gross P, Gheorghiade M, Berl T, Verbalis J, Czerwiec F . Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006; 355(20):2099-112. DOI: 10.1056/NEJMoa065181. View

16.

Sakaida I, Yamashita S, Kobayashi T, Komatsu M, Sakai T, Komorizono Y . Efficacy and safety of a 14-day administration of tolvaptan in the treatment of patients with ascites in hepatic oedema. J Int Med Res. 2013; 41(3):835-47. DOI: 10.1177/0300060513480089. View

17.

Okita K, Kawazoe S, Hasebe C, Kajimura K, Kaneko A, Okada M . Dose-finding trial of tolvaptan in liver cirrhosis patients with hepatic edema: A randomized, double-blind, placebo-controlled trial. Hepatol Res. 2013; 44(1):83-91. DOI: 10.1111/hepr.12099. View

18.

Sakaida I, Terai S, Kurosaki M, Okada M, Hirano T, Fukuta Y . Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study). J Gastroenterol. 2020; 55(8):800-810. PMC: 7376514. DOI: 10.1007/s00535-020-01691-x. View

19.

Hanai T, Shiraki M, Nishimura K, Ohnishi S, Imai K, Suetsugu A . Sarcopenia impairs prognosis of patients with liver cirrhosis. Nutrition. 2014; 31(1):193-9. DOI: 10.1016/j.nut.2014.07.005. View

20.

Mandai S, Furukawa S, Kodaka M, Hata Y, Mori T, Nomura N . Loop diuretics affect skeletal myoblast differentiation and exercise-induced muscle hypertrophy. Sci Rep. 2017; 7:46369. PMC: 5394462. DOI: 10.1038/srep46369. View