title: Clinical Factors Predicting the Effect of Tolvaptan for Refractory Ascites in Patients with Decompensated Liver Cirrhosis.
abstract: OBJECTIVE
  Refractory ascites reduces the quality of life of liver cirrhosis patients. Albumin preparation and diuretics, such as furosemide, have been used to treat refractory ascites, but the effect was poor in many patients. In this study, we analyzed patients treated with tolvaptan (TLV) at our hospital and investigated predictors of the effect.
  
  
  METHODS
  The subjects were 70 patients for whom TLV was introduced to treat refractory ascites who could be analyzed between November 2013 and March 2015 at our hospital. Patient background before initiation of oral TLV treatment, the dose of diuretics, and each item of biochemical tests of blood and urine were investigated, and factors correlated with the treatment effect were analyzed. An increase of ≥1,000 ml in the daily urine volume from the day before oral treatment or a decrease of ≥1 kg in the body weight within 7 days as an early effect was observed in 33 patients and not observed in 37 patients. TLV treatment was continued for 60 days or longer in 12 of the 37 patients in whom no early effect was observed, and the presence or absence of a delayed effect and predictors of the effect were investigated. A decrease in ascites on abdominal CT with improvement of subjective symptoms at 60 days was defined as a delayed effect.
  
  
  RESULTS
  When early predictors of the effect were investigated by univariate analysis, serum blood urea nitrogen (BUN) and serum creatinine (Cr) were significantly higher in the non-responder group (BUN: p = 0.03, Cr: p = 0.04), but no factor independently associated with the treatment effect was extracted on multivariate analysis. The delayed effect was noted in 4 (33.3%) of the 12 patients, but no predictor of the effect before treatment was identified. However, reactions, such as an increase in serum Na and reduction of urinary osmotic pressure, were observed early after TLV administration in some patients in whom the delayed effect was observed.
  
  
  CONCLUSIONS
  The diuretic effect of TLV may decrease in renal hypofunction patients. Since the delayed effect was noted in a specific ratio of patients, continuation of TLV administration is an option even though the early treatment effect is poor unless ascites aggravates or adverse effects develop.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Chishina
authors.forename: Satoru
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Naoshi
authors.initials: N
authors.lastname: Nishida
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Ueshima
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Sakurai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ida
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Minami
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takita
authors.forename: Masashi
authors.initials: M
authors.lastname: Kono
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Minami
authors.forename: Mina
authors.initials: M
authors.lastname: Iwanishi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Umehara
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yoriaki
authors.initials: Y
authors.lastname: Komeda
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Arizumi
authors.forename: Masotoshi
authors.initials: M
authors.lastname: Kudo
mesh_terms: D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists / Q000627:therapeutic use*; D001201:Ascites / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D001552:Benzazepines / Q000627:therapeutic use*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004232:Diuretics / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D006955:Hypernatremia / Q000209:etiology; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D009997:Osmotic Pressure; D011788:Quality of Life; D011860:Radiography, Abdominal / Q000379:methods; D012964:Sodium / Q000097:blood; D013148:Spironolactone / Q000008:administration & dosage / Q000627:therapeutic use; D000077602:Tolvaptan; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D000077602:Tolvaptan; D013148:Spironolactone; D005665:Furosemide; D012964:Sodium; D003404:Creatinine