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Clinical Drug Investigation
Published in: Clinical Drug Investigation 10/2016

01-10-2016 | Original Research Article

Potential Effectiveness of Tolvaptan to Improve Ascites Unresponsive to Standard Diuretics and Overall Survival in Patients with Decompensated Liver Cirrhosis

Authors: Tomoharu Yamada, Takamasa Ohki, Yuki Hayata, Yuki Karasawa, Satoshi Kawamura, Daisaku Ito, Kentaro Kojima, Michiharu Seki, Nobuo Toda, Kazumi Tagawa

Published in: Clinical Drug Investigation | Issue 10/2016

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Abstract

Background and Objective

After tolvaptan was approved for the treatment of cirrhosis patients with ascites, only a few studies have reported its efficacy in the real clinical setting, and no studies have reported its contribution to overall survival. This study clarified the clinical outcomes of tolvaptan treatment in terms of improving ascites unresponsive to standard diuretics (AUS) and overall survival.

Methods

We retrospectively enrolled 80 decompensated cirrhosis patients with AUS who were administered tolvaptan from October 2012 to December 2014. The patients were divided into two groups according to ascites improvement. We compared laboratory results and overall survival and analyzed factors that affected overall survival.

Results

Of the 80 patients, 59 (73.8 %) were male and the median age was 70 years. Thirty-nine (48.8 %) patients were Child–Pugh class C, and 36 (45.0 %) had advanced hepatocellular carcinoma (HCC). Tolvaptan was effective in 48 (60.0 %) patients with an average 3.8 kg weight reduction and ineffective in 32 (40.0 %) patients. The cumulative survival rate differed significantly between the two groups (p < 0.0001), with 87.5 and 68.0 % survival at 30 and 90 days, respectively, in the effective group, and 50.0 and 30.5 % survival, respectively, in the ineffective group. Multivariate analysis showed that improvement in AUS, advanced HCC, total bilirubin level, blood urea nitrogen level, and the presence of hyponatremia were independent predictors of overall survival.

Conclusions

Tolvaptan could possibly improve overall survival in decompensated cirrhosis patients with AUS as long as it was demonstrated to be effective in these patients.
Literature
1.
D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44(1):217–31.CrossRefPubMed
2.
3.
Sola E, Watson H, Graupera I, Turon F, Barreto R, Rodriguez E, et al. Factors related to quality of life in patients with cirrhosis and ascites: relevance of serum sodium concentration and leg edema. J Hepatol. 2012;57(6):1199–206.CrossRefPubMed
4.
Arroyo V, Colmenero J. Ascites and hepatorenal syndrome in cirrhosis: pathophysiological basis of therapy and current management. J Hepatol. 2003;38(Suppl 1):S69–89.CrossRefPubMed
5.
Planas R, Montoliu S, Balleste B, Rivera M, Miquel M, Masnou H, et al. Natural history of patients hospitalized for management of cirrhotic ascites. Clin Gastroenterol Hepatol. 2006;4(11):1385–94.CrossRefPubMed
6.
Runyon BA, Committee APG. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009;49(6):2087–107.CrossRefPubMed
7.
8.
Decaux G, Soupart A, Vassart G. Non-peptide arginine-vasopressin antagonists: the vaptans. Lancet. 2008;371(9624):1624–32.CrossRefPubMed
9.
Zmily HD, Daifallah S, Ghali JK. Tolvaptan, hyponatremia, and heart failure. Int J Nephrol Renovasc Dis. 2011;4:57–71.PubMedPubMedCentral
10.
Sakaida I, Kawazoe S, Kajimura K, Saito T, Okuse C, Takaguchi 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.CrossRefPubMed
11.
Kogiso T, Tokushige K, Hashimoto E, Ikarashi Y, Kodama K, Taniai M, et al. Safety and efficacy of long-term tolvaptan therapy for decompensated liver cirrhosis. Hepatol Res. 2016;46(3):E194–200.CrossRefPubMed
12.
Sakaida I, Nakajima K, Okita K, Hori M, Izumi T, Sakurai M, 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.CrossRefPubMedPubMedCentral
13.
Ohki T, Sato K, Yamada T, Yamagami M, Ito D, Kawanishi K, et al. Efficacy of tolvaptan in patients with refractory ascites in a clinical setting. World J Hepatol. 2015;7(12):1685–93.CrossRefPubMedPubMedCentral
14.
Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329–38.CrossRefPubMed
15.
Yamamura Y, Nakamura S, Itoh S, Hirano T, Onogawa T, Yamashita T, et al. OPC-41061, a highly potent human vasopressin V2-receptor antagonist: pharmacological profile and aquaretic effect by single and multiple oral dosing in rats. J Pharmacol Exp Ther. 1998;287(3):860–7.PubMed
16.
Wu CC, Yeung LK, Tsai WS, Tseng CF, Chu P, Huang TY, Lin YF, Lu KC. Incidence and factors predictive of acute renal failure in patients with advanced liver cirrhosis. Clin Nephrol. 2006;65(1):28–33.CrossRefPubMed
17.
Sakaida I, Yamashita S, Kobayashi T, Komatsu M, Sakai T, Komorizono Y, et al. 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.CrossRefPubMed
Metadata
Title
Potential Effectiveness of Tolvaptan to Improve Ascites Unresponsive to Standard Diuretics and Overall Survival in Patients with Decompensated Liver Cirrhosis
Authors
Tomoharu Yamada
Takamasa Ohki
Yuki Hayata
Yuki Karasawa
Satoshi Kawamura
Daisaku Ito
Kentaro Kojima
Michiharu Seki
Nobuo Toda
Kazumi Tagawa
Publication date
01-10-2016
Publisher
Springer International Publishing
Published in
Clinical Drug Investigation / Issue 10/2016
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI
https://doi.org/10.1007/s40261-016-0434-7

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