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Response criteria of tolvaptan for the treatment of hepatic edema

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

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.

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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

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Author information

Authors and Affiliations

  1. Department of Internal Medicine, Kagoshima Kouseiren Hospital, 22-25 Tenpozancho, Kagoshima, 890-0061, Japan

    Yasunari Hiramine

  2. Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0375, Japan

    Haruki Uojima

  3. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1 Kyonancho, Musashino-shi, Tokyo, 180-8610, Japan

    Hiroyuki Nakanishi & Namiki Izumi

  4. Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Akira Hiramatsu

  5. Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube-shi, Yamaguchi, 755-8505, Japan

    Takuya Iwamoto & Isao Sakaida

  6. Department of Hepatology, Sapporo Kosei General Hospital, 8-5 Kitasanzyo-higashi, Chuo-ku, Sapporo, Hokkaido, 060-0033, Japan

    Mutsuumi Kimura

  7. Third Department of Internal Medicine, Nara Medical University, 840 Shijocho, Kashihara-shi, Nara, 634-8521, Japan

    Hideto Kawaratani & Hitoshi Yoshiji

  8. Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan

    Shuji Terai

  9. Center for Digestive and Liver Diseases, Miyazaki Medical Center Hospital, 2-16 Takamatsu-cho, Miyazaki, 880-0003, Japan

    Hirofumi Uto

  10. Shunan Memorial Hospital, 1-10-1 Ikunoyaminami, Kudamatsu-shi, Yamaguchi, 744-0033, Japan

    Kiwamu Okita

  11. Department of Gastroenterology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Kazuhiko Koike

Authors
  1. Yasunari Hiramine
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  2. Haruki Uojima
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  3. Hiroyuki Nakanishi
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  4. Akira Hiramatsu
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  7. Hideto Kawaratani
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  8. Shuji Terai
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  10. Hirofumi Uto
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  11. Isao Sakaida
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  12. Namiki Izumi
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  14. Kazuhiko Koike
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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.

Corresponding author

Correspondence to Yasunari Hiramine.

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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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Hiramine, Y., Uojima, H., Nakanishi, H. et al. Response criteria of tolvaptan for the treatment of hepatic edema. J Gastroenterol 53, 258–268 (2018). https://doi.org/10.1007/s00535-017-1366-6

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  • DOI: https://doi.org/10.1007/s00535-017-1366-6

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