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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2015; 21(41): 11584-11596
Published online Nov 7, 2015. doi: 10.3748/wjg.v21.i41.11584
Do vasopressin V2 receptor antagonists benefit cirrhotics with refractory ascites?
Hiroshi Fukui
Hiroshi Fukui, Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Kashihara, Nara 634-8522, Japan
Author contributions: Fukui H wrote this review.
Conflict-of-interest statement: The author has received fees for serving as a speaker and a moderator of several meetings from Otsuka Pharmaceutical Co., Ltd.
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:
Correspondence to: Hiroshi Fukui, MD, PhD, Professor emeritus, Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
Telephone: +81-744-223051 Fax: +81-744-247122
Received: May 8, 2015
Peer-review started: May 11, 2015
First decision: July 13, 2015
Revised: August 8, 2015
Accepted: September 15, 2015
Article in press: September 15, 2015
Published online: November 7, 2015

Hyponatremia is a frequent complication of advanced cirrhosis with ascites associated with increased morbidity and mortality. It is caused by an impairment in the renal capacity to eliminate solute-free water and is considered to be related to persistent secretion of vasopressin despite low serum osmolality. This nonosmotic release of vasopressin is mediated by the autonomic nervous system, which senses the underfilling of arterial vascular component. This reduction of effective arterial blood volume is closely related to the development of ascites. Although the short-time effects of vasopressin V2 receptor antagonists (vaptans) on hyponatremia and ascites have been repeatedly reported, their effects on the long-term management of cirrhotic ascites have not been established yet. Considering that their effects on water diuresis and their safety are limited by severe underfilling state of patients, cautious approaches with adequate monitoring are needed to advanced cirrhosis. Proper indication, adequate doses and new possibility of combination therapy should be explored in the future controlled study. As hyponatremia is frequent obstacle to ascites management, judicious combination with low-dose diuretics may decrease the incidence of refractory ascites. Although vaptans show much promise in the treatment of advanced cirrhosis, the problem of high cost should be solved for the future.

Keywords: Liver cirrhosis, Ascites, Hyponatremia, Pathophysiology, V2 receptor antagonist

Core tip: Dilutional hyponatremia is a frequent complication with high morbidity and mortality in advanced liver cirrhosis with ascites. It is attributable to disturbed water excretion related to enhanced vasopressin activity on the background of underfilling state in the splanchnic arterial circulation. V2 receptor antagonist is theoretically promising for the future treatment of hyponatremia and ascites. The present review aimed to summarize the pathophysiological backgrounds of ascites and hyponatremia and to introduce major results of all controlled trials. Although there existed several unsolved problems and controversies on the topic, discussions from the basic standpoints may light up the dark road.