Display options
Share it on

World J Hepatol. 2015 Jun 28;7(12):1685-93. doi: 10.4254/wjh.v7.i12.1685.

Efficacy of tolvaptan in patients with refractory ascites in a clinical setting.

World journal of hepatology

Takamasa Ohki, Koki Sato, Tomoharu Yamada, Mari Yamagami, Daisaku Ito, Koki Kawanishi, Kentaro Kojima, Michiharu Seki, Nobuo Toda, Kazumi Tagawa

Affiliations

  1. 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.

PMID: 26140088 PMCID: PMC4483550 DOI: 10.4254/wjh.v7.i12.1685

Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Decompensated cirrhosis; Paracentesis; Refractory ascites; Tolvaptan

References

  1. Hepatol Res. 2014 Jan;44(1):73-82 - PubMed
  2. J Hepatol. 2012 Dec;57(6):1199-206 - PubMed
  3. Hepatol Res. 2015 Jul;45(7):739-44 - PubMed
  4. Hepatology. 2013 Apr;57(4):1651-3 - PubMed
  5. Future Cardiol. 2006 Nov;2(6):627-34 - PubMed
  6. World J Gastroenterol. 2014 Aug 28;20(32):11400-5 - PubMed
  7. Gastroenterology. 2003 Mar;124(3):634-41 - PubMed
  8. Cleve Clin J Med. 2010 Oct;77(10):715-26 - PubMed
  9. Clin Gastroenterol Hepatol. 2006 Nov;4(11):1385-94 - PubMed
  10. Hepatology. 2003 Jul;38(1):258-66 - PubMed
  11. Lancet. 2008 May 10;371(9624):1624-32 - PubMed
  12. N Engl J Med. 2004 Apr 15;350(16):1646-54 - PubMed
  13. J Int Med Res. 2013 Jun;41(3):835-47 - PubMed
  14. Hepatology. 1996 Jan;23(1):164-76 - PubMed
  15. Cardiology. 2009;113(1):12-9 - PubMed
  16. Expert Opin Pharmacother. 2011 Apr;12(6):961-76 - PubMed
  17. Gastroenterology. 1988 Jun;94(6):1493-502 - PubMed
  18. J Am Coll Cardiol. 2008 Jan 22;51(3):300-6 - PubMed
  19. Z Gastroenterol. 2001 Jan;39(1):5-10 - PubMed
  20. Circ J. 2013;77(2):397-404 - PubMed
  21. Hepatol Res. 2014 Jan;44(1):83-91 - PubMed
  22. N Engl J Med. 1991 Sep 19;325(12):829-35 - PubMed
  23. N Engl J Med. 2006 Nov 16;355(20):2099-112 - PubMed

Publication Types