Clinical efficacy of tolvaptan for treatment of refractory ascites in liver cirrhosis patients

Zhang, Xin; Wang, Shuzhen; Zheng, Jun-Fu; Zhao, Wenling; Li, Peng; Fan, Chongxi; Li, Bing; Dong, Paul R; Li, Lei; Ding, Huiguo

doi:10.3748/wjg.v20.i32.11400

Cited by 36 publications

(30 citation statements)

References 25 publications

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“…Zhang et al [10] investigated 39 patients with liver cirrhosis-associated refractory ascites and observed that the effect of TLV decreased in hepatorenal syndrome (HRS) patients. In a TLV single-dose study involving renal failure patients, the effect decreased as estimated glomerular filtration rate (eGFR) decreased [11].…”

Section: Discussionmentioning

confidence: 99%

Clinical Factors Predicting the Effect of Tolvaptan for Refractory Ascites in Patients with Decompensated Liver Cirrhosis

Chishina¹,

Hagiwara²,

Nishida³

et al. 2016

Dig Dis

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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.

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Section: Discussionmentioning

confidence: 99%

Clinical Factors Predicting the Effect of Tolvaptan for Refractory Ascites in Patients with Decompensated Liver Cirrhosis

Chishina¹,

Hagiwara²,

Nishida³

et al. 2016

Dig Dis

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“…In contrast to furosemide, tolvaptan results in urine output without decreasing renal blood flow, and it seems to not activate the sympathetic nervous system or the RAAS, as it induces the excretion of electrolyte‐free water without changing the total level of electrolyte excretion . Recently, several studies have evaluated the effects of low doses of tolvaptan for treating liver cirrhosis patients . Assuming a more prominent role in decompensated liver cirrhosis, the response to this drug is unpredictable.…”

Section: Introductionmentioning

confidence: 99%

Close correlation between urinary sodium excretion and response to tolvaptan in liver cirrhosis patients with ascites

Uojima

Kinbara

Hidaka

et al. 2016

Hepatology Research

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Aim: To assess the correlation between response to tolvaptan and treatment-related factors in liver cirrhosis patients.Methods: This single-center retrospective study was carried out at Shonan Kamakura General Hospital in Kanagawa, Japan, between October 2013 and September 2015. Forty-three liver cirrhosis patients (mean age, 65.7 years) with insufficient responses to conventional diuretics for at least 7 days were enrolled. All patients received oral tolvaptan (7.5 mg/day for 7 days) and guideline-directed medical therapy including sodium intake restrictions. A responder to tolvaptan was defined as a patient having a ≥2-kg decrease in body weight 1 week after commencing drug treatment, and a non-responder was defined as a patient not losing ≥2 kg in body weight 1 week after commencing treatment. We investigated the correlation of change in body weight for 1 week after drug administration compared to baseline clinical characteristics. Results:The mean body weight change from the baseline on the final dosing day was À2.47 ± 3.34 kg (P < 0.0001). There were 20 (46.5%) responders to tolvaptan. Urinary sodium and volume excretion was higher in responders than in non-responders (108.2 ± 70.5 vs 42.6 ± 36.7, P = 0.0003; 1462.8 ± 625.7 vs 960.9 ± 600.6, P = 0.0073). Logistic regression analyses for responders to tolvaptan were carried out, and independent correlation of the responders was urinary sodium excretion (P = 0.0114; hazard ratio, 0.9418; 95% confidence interval, 0.8768À0.9896) in the multivariate analyses. Conclusion:In decompensated liver cirrhosis patients, urinary excretion sodium showed good correlation with tolvaptan response.

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“…Furthermore, use of satavaptan was associated with an increased mortality and the drug was withdrawn from development. Although a number of studies have valuated tolvaptan for the management of refractory ascites in patients with cirrhosis [43][44][45] , a major drawback of this drug is that there is a 23% risk of serious hepatic adverse events occurring with tolvaptan and thus, the FDA placed a black box warning on the drug limiting its use to patients with liver disease [46,47] .…”

Section: Vaptansmentioning

confidence: 99%

Translating Our Current Understanding of Ascites Management into New Therapies for Patients with Cirrhosis and Fluid Retention

Pose

Cárdenas²

2017

Dig Dis

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Ascites is the most common complication associated with cirrhosis resulting in poor quality of life, high risk of development of other complications of cirrhosis, increased morbidity and mortality associated with surgical interventions, and poor long-term outcome. Patients with cirrhosis and a first onset of ascites, have a probability of survival of 85% during the first year and 56% at 5 years without liver transplantation. Ascites is caused due to increased renal sodium retention as a result of increased activity of the renin-angiotensin-aldosterone system in response to marked vasodilation of the splanchnic circulation. The practical management of ascites involves the proper evaluation of a patient with a thorough history and physical exam. In addition, complete laboratory, ascitic fluid, and radiological tests should be performed. One of the most important steps in the initial assessment of patients with ascites is to refer the appropriate candidates for liver transplantation, as it offers a definitive cure for cirrhosis and its complications. While the initial management of uncomplicated ascites with low sodium diet and diuretic treatment is straightforward in a majority of patients, approximately 10% of patients fail to respond to diuretics and become a real therapeutic challenge. The initial treatment of choice in patients with refractory ascites is large-volume paracentesis (LVP) associated with intravenous albumin; some patients also benefit from transjugular intrahepatic portosystemic shunts (TIPS). When repeated LVP or TIPS cannot be performed, other approaches using vasoconstrictors such as midodrine can be considered although data are scarce. A newly designed automated low flow pump system (Alfapump), which is designed to move ascites from the peritoneal cavity to the urinary bladder where it is eliminated spontaneously through diuresis is promising, but the data are also limited and safety is still a matter of concern. This article focuses on the practical aspects of the evaluation and treatment of patients with ascites and cirrhosis and also discusses how to translate our current understanding of ascites pathophysiology into new treatment methods for patients with fluid retention.

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Clinical efficacy of tolvaptan for treatment of refractory ascites in liver cirrhosis patients

Abstract: Tolvaptan is a promising aquaretic for the treatment of refractory ascites in patients with decompensated liver cirrhosis.

Cited by 36 publications

References 25 publications

Clinical Factors Predicting the Effect of Tolvaptan for Refractory Ascites in Patients with Decompensated Liver Cirrhosis

Clinical Factors Predicting the Effect of Tolvaptan for Refractory Ascites in Patients with Decompensated Liver Cirrhosis

Close correlation between urinary sodium excretion and response to tolvaptan in liver cirrhosis patients with ascites

Translating Our Current Understanding of Ascites Management into New Therapies for Patients with Cirrhosis and Fluid Retention

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