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Journal of Gastroenterology

, Volume 53, Issue 2, pp 258–268 | Cite as

Response criteria of tolvaptan for the treatment of hepatic edema

  • Yasunari HiramineEmail author
  • Haruki Uojima
  • Hiroyuki Nakanishi
  • Akira Hiramatsu
  • Takuya Iwamoto
  • Mutsuumi Kimura
  • Hideto Kawaratani
  • Shuji Terai
  • Hitoshi Yoshiji
  • Hirofumi Uto
  • Isao Sakaida
  • Namiki Izumi
  • Kiwamu Okita
  • Kazuhiko Koike
Original Article—Liver, Pancreas, and Biliary Tract

Abstract

Background

Although tolvaptan is an effective treatment for hepatic edema, there are no established criteria for assessment of the therapeutic effect. The present study evaluates the association between body weight change and clinical symptoms to identify an effective indicator of tolvaptan response.

Methods

The study comprised 460 patients. The first data set contained 147 patients with hepatic edema who received tolvaptan in Kagoshima Kouseiren Hospital, a representative institution of this study. From these data, an optimal cutoff value of body weight change, which accurately indicated symptom reduction, was identified. The response rates obtained based on the cutoff value were evaluated by receiver-operating characteristic (ROC) analysis and kappa coefficients. The kappa coefficient was then validated internally using the bootstrap method and externally using the validation data set of 313 patients from four other hospitals.

Results

A cutoff value for body weight loss of 1.5 kg/week produced the largest area under the ROC curve (0.961; sensitivity, 89.8%; specificity, 92.0%) and a high kappa coefficient (0.831). The correlation between symptom reduction and body weight loss of 1.5 kg/week was evaluated internally and externally, and the cutoff value was validated.

Conclusions

The cutoff value of body weight change that most accurately reflected symptom reduction was 1.5 kg/week; this value is expected to be an effective indicator of response to tolvaptan in clinical practice.

Keywords

Tolvaptan Hepatic edema Body weight loss Cutoff value Clinical findings 

Abbreviations

ROC

Receiver-operating characteristic

AQP2

Aquaporin 2

AUC

Area under the ROC curve

ASI-7

Ascites Symptom Inventory-7

CLDQ

Chronic Liver Disease Questionnaire

Notes

Author contributions

YH, HU, HN, AH, TI, MK, ST, HY, KO, and KK conceived of the study and participated in its design and coordination. YH, HU, HN, AH, MK, HK, and TI conducted the data analysis. YH interpreted the findings and drafted the original manuscript. HU, HY, ST, KO, and KK edited the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

HN, ST, IS, NI, KO and KK have received honoraria from Otsuka Pharmaceutical Co., Ltd. The other authors declare that they have no conflict of interest.

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Copyright information

© Japanese Society of Gastroenterology 2017

Authors and Affiliations

  • Yasunari Hiramine
    • 1
    Email author
  • Haruki Uojima
    • 2
  • Hiroyuki Nakanishi
    • 3
  • Akira Hiramatsu
    • 4
  • Takuya Iwamoto
    • 5
  • Mutsuumi Kimura
    • 6
  • Hideto Kawaratani
    • 7
  • Shuji Terai
    • 8
  • Hitoshi Yoshiji
    • 7
  • Hirofumi Uto
    • 9
  • Isao Sakaida
    • 5
  • Namiki Izumi
    • 3
  • Kiwamu Okita
    • 10
  • Kazuhiko Koike
    • 11
  1. 1.Department of Internal MedicineKagoshima Kouseiren HospitalKagoshimaJapan
  2. 2.Department of Gastroenterology, Internal MedicineKitasato University School of MedicineSagamiharaJapan
  3. 3.Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
  4. 4.Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  5. 5.Department of Gastroenterology and HepatologyYamaguchi University Graduate School of MedicineYamaguchiJapan
  6. 6.Department of HepatologySapporo Kosei General HospitalSapporoJapan
  7. 7.Third Department of Internal MedicineNara Medical UniversityNaraJapan
  8. 8.Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental SciencesNiigata UniversityNiigataJapan
  9. 9.Center for Digestive and Liver DiseasesMiyazaki Medical Center HospitalMiyazakiJapan
  10. 10.Shunan Memorial HospitalYamaguchiJapan
  11. 11.Department of GastroenterologyThe University of TokyoTokyoJapan

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