title: Efficacy of tolvaptan in patients with refractory ascites in a clinical setting.
abstract: OBJECTIVE
  To elucidate the efficacies of tolvaptan (TLV) as a treatment for refractory ascites compared with conventional treatment.
  
  
  METHODS
  We retrospectively enrolled 120 refractory ascites patients between January 1, 2009 and September 31, 2014. Sixty patients were treated with oral TLV at a starting dose of 3.75 mg/d in addition to sodium restriction (> 7 g/d), albumin infusion (10-20 g/wk), and standard diuretic therapy (20-60 mg/d furosemide and 25-50 mg/d spironolactone) and 60 patients with large volume paracentesis in addition to sodium restriction (less than 7 g/d), albumin infusion (10-20 g/wk), and standard diuretic therapy (20-120 mg/d furosemide and 25-150 mg/d spironolactone). Patient demographics and laboratory data, including liver function, were not matched due to the small number of patients. Continuous variables were analyzed by unpaired t-test or paired t-test. Fisher's exact test was applied in cases comparing two nominal variables. We analyzed factors affecting clinical outcomes using receiver operating characteristic curves and multivariate regression analysis. We also used multivariate Cox's proportional hazard regression analysis to elucidate the risk factors that contributed to the increased incidence of ascites.
  
  
  RESULTS
  TLV was effective in 38 (63.3%) patients. The best cut-off values for urine output and reduced urine osmolality as measures of refractory ascites improvement were > 1800 mL within the first 24 h and > 30%, respectively. Multivariate regression analysis indicated that > 25% reduced urine osmolality [odds ratio (OR) = 20.7; P < 0.01] and positive hepatitis C viral antibodies (OR = 5.93; P = 0.05) were positively correlated with an improvement of refractory ascites, while the total bilirubin level per 1.0 mg/dL (OR = 0.57; P = 0.02) was negatively correlated with improvement. In comparing the TLV group and controls, only the serum sodium level was significantly lower in the TLV group (133 mEq/L vs 136 mEq/L; P = 0.02). However, there were no significant differences in the other parameters between the two groups. The cumulative incidence rate was significantly higher in the control group with a median incidence time of 30 d in the TLV group and 20 d in the control group (P = 0.01). Cox hazard proportional multivariate analysis indicated that the use of TLV (OR = 0.58; P < 0.01), uncontrolled liver neoplasms (OR = 1.92; P < 0.01), total bilirubin level per 1.0 mg/dL (OR = 1.10; P < 0.01), and higher sodium level per 1.0 mEq/L (OR = 0.94; P < 0.01) were independent factors that contributed to incidence.
  
  
  CONCLUSIONS
  Administration of TLV results in better control of refractory ascites and reduced the incidence of additional invasive procedures or hospitalization compared with conventional ascites treatments.
authors.affiliation: Takamasa Ohki, Koki Sato, Tomoharu Yamada, Mari Yamagami, Daisaku Ito, Koki Kawanishi, Kentaro Kojima, Michiharu Seki, Nobuo Toda, Kazumi Tagawa, Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo 101-8643, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Ohki
authors.affiliation: Takamasa Ohki, Koki Sato, Tomoharu Yamada, Mari Yamagami, Daisaku Ito, Koki Kawanishi, Kentaro Kojima, Michiharu Seki, Nobuo Toda, Kazumi Tagawa, Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo 101-8643, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Sato
authors.affiliation: Takamasa Ohki, Koki Sato, Tomoharu Yamada, Mari Yamagami, Daisaku Ito, Koki Kawanishi, Kentaro Kojima, Michiharu Seki, Nobuo Toda, Kazumi Tagawa, Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo 101-8643, Japan.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Takamasa Ohki, Koki Sato, Tomoharu Yamada, Mari Yamagami, Daisaku Ito, Koki Kawanishi, Kentaro Kojima, Michiharu Seki, Nobuo Toda, Kazumi Tagawa, Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo 101-8643, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Yamagami
authors.affiliation: Takamasa Ohki, Koki Sato, Tomoharu Yamada, Mari Yamagami, Daisaku Ito, Koki Kawanishi, Kentaro Kojima, Michiharu Seki, Nobuo Toda, Kazumi Tagawa, Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo 101-8643, Japan.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Ito
authors.affiliation: Takamasa Ohki, Koki Sato, Tomoharu Yamada, Mari Yamagami, Daisaku Ito, Koki Kawanishi, Kentaro Kojima, Michiharu Seki, Nobuo Toda, Kazumi Tagawa, Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo 101-8643, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Kawanishi
authors.affiliation: Takamasa Ohki, Koki Sato, Tomoharu Yamada, Mari Yamagami, Daisaku Ito, Koki Kawanishi, Kentaro Kojima, Michiharu Seki, Nobuo Toda, Kazumi Tagawa, Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo 101-8643, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kojima
authors.affiliation: Takamasa Ohki, Koki Sato, Tomoharu Yamada, Mari Yamagami, Daisaku Ito, Koki Kawanishi, Kentaro Kojima, Michiharu Seki, Nobuo Toda, Kazumi Tagawa, Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo 101-8643, Japan.
authors.forename: Michiharu
authors.initials: M
authors.lastname: Seki
authors.affiliation: Takamasa Ohki, Koki Sato, Tomoharu Yamada, Mari Yamagami, Daisaku Ito, Koki Kawanishi, Kentaro Kojima, Michiharu Seki, Nobuo Toda, Kazumi Tagawa, Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo 101-8643, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Toda
authors.affiliation: Takamasa Ohki, Koki Sato, Tomoharu Yamada, Mari Yamagami, Daisaku Ito, Koki Kawanishi, Kentaro Kojima, Michiharu Seki, Nobuo Toda, Kazumi Tagawa, Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo 101-8643, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Tagawa
keywords: Decompensated cirrhosis; Paracentesis; Refractory ascites; Tolvaptan