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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Relationship between response to lusutrombopag and splenic volume
Haruki Uojima, Yoshitaka Arase, Norio Itokawa, Masanori Atsukawa, Takashi Satoh, Koji Miyazaki, Hisashi Hidaka, Ji Hyun Sung, Makoto Kako, Kota Tsuruya, Tatehiro Kagawa, Katsuhiko Iwakiri, Ryouichi Horie, Wasaburo Koizumi
Haruki Uojima, Ji Hyun Sung, Makoto Kako, Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan
Haruki Uojima, Hisashi Hidaka, Wasaburo Koizumi, Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Kanagawa 252-0375, Japan
Yoshitaka Arase, Kota Tsuruya, Tatehiro Kagawa, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa 259-1193, Japan
Norio Itokawa, Department of Internal Medicine, Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Chiba 270-1694, Japan
Masanori Atsukawa, Katsuhiko Iwakiri, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo 113-8603, Japan
Takashi Satoh, Ryouichi Horie, Division of Hematology, Department of Medical Laboratory Sciences, Kitasato University School of Allied Health Sciences, Kanagawa 252-0375, Japan
Takashi Satoh, Ryouichi Horie, Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences, Kanagawa 252-0375, Japan
Koji Miyazaki, Department of Transfusion and Cell Transplantation, Kitasato University School of Medicine, Kanagawa 252-0375, Japan
Author contributions: Uojima H, Arase Y, Itokawa N, Atsukawa M, Satoh T, Miyazaki K, Hidaka H, Sung JH, Kako M, Tsuruya K, Kagawa T, Iwakiri K, Horie R, and Koizumi W contributed equally to this work; Uojima H, Arase Y, and Itokawa N collected and analyzed the data; Uojima H drafted the manuscript; Hidaka H designed and supervised the study; Atsukawa M, Satoh T, Miyazaki K, Kako M, Tsuruya K, Kagawa T, Iwakiri K, Horie R, and Koizumi W offered technical or material support; all authors discussed the results and commented on the manuscript.
Institutional review board statement: The study was reviewed and approved by the Tokushukai Group Ethical Committee’s institutional review board.
Informed consent statement: This study is a retrospective observational study. Informed consent was obtained from all individual participants included in the study by the opt-out method of our hospital website.
Conflict-of-interest statement: We declare no conflicts of interest.
Data sharing statement: The technical appendix, statistical code, and dataset are available from the corresponding author (email: kiruha@kitasato-u.ac.jp).
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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/
Corresponding author to: Haruki Uojima, MD, PhD, Doctor, Department of Gastroenterology, Shonankamakura General Hospital, 1370-1 Okamoto, Kamakura, Kanagawa 247-8533, Japan. kiruha@kitasato-u.ac.jp
Telephone: +81-467-461717 Fax: +81-467-450190
Received: September 12, 2018
Peer-review started: September 12, 2018
First decision: October 14, 2018
Revised: October 20, 2018
Accepted: November 9, 2018
Article in press: November 9, 2018
Published online: December 14, 2018
ARTICLE HIGHLIGHTS
Research background
Lusutrombopag is an oral, small-molecule thrombopoietin (TPO) receptor agonist (TPO-RA) used for the treatment of thrombocytopenic patients with chronic liver diseases. TPO in the peripheral blood in advanced-stage liver disease was been reduced severely. Therefore, patients with inadequate TPO production due to chronic liver disease are the principal targets of lusutrombopag.
Research motivation
The response to lusutrombopag is unpredictable, assuming that the drug exerts more dramatic effects in thrombocytopenia associated with severe liver disease prior to invasive surgery.
Research objectives
The study aimed to assess the correlation between the clinical characteristics of patients with chronic liver disease and the efficacy of lusutrombopag treatment.
Research methods
This multicenter retrospective study was conducted at four locations in Japan. This study enrolled thrombocytopenic patients who received oral lusutrombopag. We evaluated the response to lusutrombopag compared to baseline clinical characteristics in patients with chronic liver disease.
Research results
Splenic volume and body weight were lower in the responder group than in the non-responder group. Using a logistic regression model to assess the relationship between response to lusutrombopag and clinical characteristics, multivariate analysis confirmed that splenic volume was an independent factor that predicted the response of platelet counts (P = 0.025, odds ratio: 11.2; 95%CI: 1.354-103.0). Splenic volume was negatively correlated to changes in platelet count (r = -0.524, P = 0.001).
Research conclusions
Splenic volume influences change in platelet counts after administration of lusutrombopag in patients with chronic liver disease. Larger spleen size appears to reduce the effect of lusutrombopag in terms of platelet count. Splenic volume should be taken into consideration when administering lusutrombopag to ensure that patients receive the optimal treatment. This is the first report to assess the factors that affect the response to lusutrombopag in patients with chronic liver disease. There are multiple factors which can cause thrombocytopenia in patients with chronic liver disease. These factors include anti-platelet antibodies, levels or activity of thrombopoietin, and bone marrow suppression of thrombopoiesis due to myelodysplastic syndromes and/or direct myelosuppressive effects of HCV infection. In this study, the evaluation of influences of these factors was lacking. Therefore, further studies are warranted.
Research perspectives
Splenic volume should be taken into consideration when administering lusutrombopag to ensure that patients receive optimal treatment. It is not clear whether or not the combination therapy improves the long-term prognosis of these patients. Therefore, future long-term observational studies are warranted. Further studies are desired to assess multiple factors include anti-platelet antibodies, levels or activity of thrombopoietin, and bone marrow suppression of thrombopoiesis due to myelodysplastic syndromes and/or direct myelosuppressive effects of HCV infection.
