Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 28, 2015; 7(12): 1685-1693
Published online Jun 28, 2015. doi: 10.4254/wjh.v7.i12.1685
Efficacy of tolvaptan in patients with refractory ascites in a clinical setting
Takamasa Ohki, Koki Sato, Tomoharu Yamada, Mari Yamagami, Daisaku Ito, Koki Kawanishi, Kentaro Kojima, Michiharu Seki, Nobuo Toda, Kazumi Tagawa
Takamasa Ohki, Koki Sato, Tomoharu Yamada, Mari Yamagami, Daisaku Ito, Koki Kawanishi, Kentaro Kojima, Michiharu Seki, Nobuo Toda, Kazumi Tagawa, Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo 101-8643, Japan
Author contributions: All authors contributed to this paper.
Ethics approval: This is a retrospective study. We have no statement about institutional review board.
Informed consent: For this type of retrospective study formal consent is not required.
Conflict-of-interest: We have no conflict of interests.
Data sharing: Technical appendix, statistical code, and dataset available from the corresponding author at following e-mail address (anb72547@nifty.com). Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Takamasa Ohki, MD, PhD, Department of Gastroenterology, Mitsui Memorial Hospital, 1 Kandaizumicho, Chiyoda-ku, Tokyo 101-8643, Japan. anb72547@nifty.com
Telephone: +81-3-38629111
Received: March 5, 2015
Peer-review started: March 6, 2015
First decision: April 17, 2015
Revised: May 11, 2015
Accepted: June 9, 2015
Article in press: June 11, 2015
Published online: June 28, 2015
Processing time: 115 Days and 23.1 Hours
Abstract

AIM: To elucidate the efficacies of tolvaptan (TLV) as a treatment for refractory ascites compared with conventional treatment.

METHODS: We retrospectively enrolled 120 refractory ascites patients between January 1, 2009 and September 31, 2014. Sixty patients were treated with oral TLV at a starting dose of 3.75 mg/d in addition to sodium restriction (> 7 g/d), albumin infusion (10-20 g/wk), and standard diuretic therapy (20-60 mg/d furosemide and 25-50 mg/d spironolactone) and 60 patients with large volume paracentesis in addition to sodium restriction (less than 7 g/d), albumin infusion (10-20 g/wk), and standard diuretic therapy (20-120 mg/d furosemide and 25-150 mg/d spironolactone). Patient demographics and laboratory data, including liver function, were not matched due to the small number of patients. Continuous variables were analyzed by unpaired t-test or paired t-test. Fisher’s exact test was applied in cases comparing two nominal variables. We analyzed factors affecting clinical outcomes using receiver operating characteristic curves and multivariate regression analysis. We also used multivariate Cox’s proportional hazard regression analysis to elucidate the risk factors that contributed to the increased incidence of ascites.

RESULTS: TLV was effective in 38 (63.3%) patients. The best cut-off values for urine output and reduced urine osmolality as measures of refractory ascites improvement were > 1800 mL within the first 24 h and > 30%, respectively. Multivariate regression analysis indicated that > 25% reduced urine osmolality [odds ratio (OR) = 20.7; P < 0.01] and positive hepatitis C viral antibodies (OR = 5.93; P = 0.05) were positively correlated with an improvement of refractory ascites, while the total bilirubin level per 1.0 mg/dL (OR = 0.57; P = 0.02) was negatively correlated with improvement. In comparing the TLV group and controls, only the serum sodium level was significantly lower in the TLV group (133 mEq/L vs 136 mEq/L; P = 0.02). However, there were no significant differences in the other parameters between the two groups. The cumulative incidence rate was significantly higher in the control group with a median incidence time of 30 d in the TLV group and 20 d in the control group (P = 0.01). Cox hazard proportional multivariate analysis indicated that the use of TLV (OR = 0.58; P < 0.01), uncontrolled liver neoplasms (OR = 1.92; P < 0.01), total bilirubin level per 1.0 mg/dL (OR = 1.10; P < 0.01), and higher sodium level per 1.0 mEq/L (OR = 0.94; P < 0.01) were independent factors that contributed to incidence.

CONCLUSION: Administration of TLV results in better control of refractory ascites and reduced the incidence of additional invasive procedures or hospitalization compared with conventional ascites treatments.

Keywords: Refractory ascites; Tolvaptan; Paracentesis; Decompensated cirrhosis

Core tip: Tolvaptan (TLV) was effective in 38 (63.3%) refractory ascites patients. The best cut-off values for urine output and reduced urine osmolality as measures of refractory ascites improvement were > 1800 mL within the first 24 h and > 30%, respectively. The cumulative incidence rate was significantly higher in the control group with a median incidence time of 30 d in the TLV group and 20 d in the control group. Administration of TLV results in better control of refractory ascites and reduced the incidence of additional invasive procedures or hospitalization compared with conventional ascites treatments.