Prospective Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2016; 22(21): 5104-5113
Published online Jun 7, 2016. doi: 10.3748/wjg.v22.i21.5104
Usefulness of portal vein pressure for predicting the effects of tolvaptan in cirrhotic patients
Ai Nakagawa, Masanori Atsukawa, Akihito Tsubota, Chisa Kondo, Tomomi Okubo, Taeang Arai, Norio Itokawa, Yoshiyuki Narahara, Katsuhiko Iwakiri
Ai Nakagawa, Masanori Atsukawa, Chisa Kondo, Tomomi Okubo, Taeang Arai, Norio Itokawa, Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba 270-1694, Japan
Akihito Tsubota, Core Research Facilities for Basic Science, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo 105-8471, Japan
Yoshiyuki Narahara, Katsuhiko Iwakiri, Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, Tokyo 113-8603, Japan
Author contributions: Nakagawa A, Atsukawa M, Kondo C, Okubo T, Arai T and Itokawa N designed the study and measured porta vein pressure; Atsukawa M and Tsubota A contributed equally to the preparation of this manuscript; Tsubota A, Narahara Y and Iwakiri K supervised the study; all authors have read and approved the final version to be published.
Institutional review board statement: The protocol was approved by the Ethics Review Board of Nippon Medical School Chiba Hokusoh Hospital (approval No. 526012). All patients and their families received a sufficient explanation of the aim and contents of this study before the entry.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Informed consent statement: All patients and their families received a sufficient explanation of the aim and contents of this study before the entry. Patients who provided written informed consent participated in this study. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with Helsinki Declaration of 1975, as revised in 2008.
Data sharing statement: No additional data are available.
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: Masanori Atsukawa, MD, PhD, Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, 1715, Kamakari, Inzai, Chiba 270-1694, Japan. momogachi@yahoo.co.jp
Telephone: +81-4-76991111 Fax: +81-4-769911111908
Received: February 23, 2016
Peer-review started: February 23, 2016
First decision: March 7, 2016
Revised: March 19, 2016
Accepted: March 30, 2016
Article in press: March 30, 2016
Published online: June 7, 2016
Abstract

AIM: To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention.

METHODS: We herein conducted this study to clarify the influencing factors in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient (HVPG) value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response.

RESULTS: Subjects comprised patients with a median age of 65 (range, 40-82) years. According to the Child-Pugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were -1.0 kg (P = 2.04 × 10-6) and -1.3 kg (P = 1.83 × 10-5), respectively. The median HVPG value was 240 (range, 105-580) mmH2O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mmH2O in predicting treatment response. The response rate was 87.5% (7/8) in patients with HVPG of 190 mmH2O or less, whereas it was only 12.5% (2/16) in those with HVPG of greater than 190 mmH2O (P = 7.46 × 10-4). We compared each characteristics factors between responders and non-responders. As a result, HVPG (P = 0.045) and serum hyaluronic acid (P = 0.017) were detected as useful factors.

CONCLUSION: The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.

Keywords: Tolvaptan, V2 receptor antagonist, Portal vein pressure, Hepatic venous pressure gradient, Decompensated chirrosis

Core tip: To clarify the factors influencing the effect of tolvaptan, a V2 receptor antagonist, in patients with decompensated liver cirrhosis complicated by liquid retention, we conducted this study. As a result, hepatic venous pressure gradient (HVPG) was the only significant factor that influenced the weight loss effect of tolvaptan. The response rate was 87.5% (7/8) in patients with HVPG of 190 mmH2O or less, whereas it was only 12.5% (2/16) in those with HVPG of greater than 190 mmH2O. The present study suggests that tolvaptan in the treatment of liquid retention related to decompensated liver cirrhosis could be more effective for patients with lower portal vein pressure.