Tolvaptan is effective in treating patients with refractory ascites due to cirrhosis

Tahara, Toshiyuki; Mori, Kiyoto; Mochizuki, Mari; Ishiyama, Ryoko; Noda, Marin; Hoshi, Hitomi; Lefor, Alan Kawarai; Shinozaki, Satoshi

doi:10.3892/br.2017.1005

Cited by 11 publications

(17 citation statements)

References 21 publications

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“…There was no report that tolvaptan was associated with longer survival time in patients with heart failure [19][20]. On the other hand, some reports showed that tolvaptan responders were associated with longer survival time in cirrhotic patients [8,[21][22][23]. Tahara et al [23] reported that tolvaptan response was associated with longer survival time, and renal function (an eGFR ≥55 mL/min) was one of the significant predictors of response.…”

Section: Discussionmentioning

confidence: 98%

“…On the other hand, some reports showed that tolvaptan responders were associated with longer survival time in cirrhotic patients [8,[21][22][23]. Tahara et al [23] reported that tolvaptan response was associated with longer survival time, and renal function (an eGFR ≥55 mL/min) was one of the significant predictors of response. Our results were consistent with their report in these points.…”

Section: Discussionmentioning

confidence: 99%

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Positive Response to Tolvaptan Treatment Would Be a Good Prognostic Factor for Cirrhotic Patients with Ascites

Kida¹

2019

Dig Dis

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Aims: Ascites is one of the major complications in advanced cirrhotic patients. Tolvaptan is a non-peptide orally available arginine vasopressin V2 receptor antagonist. We investigated and found that tolvaptan therapy improved the prognosis and predictive factor of cirrhotic patients with ascites. Methods: Overall, 99 patients with newly diagnosed ascites with cirrhosis were enrolled. No patients had intrahepatic malignancy. The patients were divided into 2 groups based on tolvaptan therapy: 86 patients treated with tolvaptan (tolvaptan-group) and 13 patients treated without tolvaptan (non-tolvaptan-group). Tolvaptan-responder was defined as body weight loss of ≥1.5 kg/week after administering tolvaptan. Results: Tolvaptan therapy was effective in 61.6% of cirrhotic patients. There was a significant difference in the overall survival (OS) between the tolvaptan-responder-group and the other groups (p < 0.001). Male (HR 5.05; p = 0.01), tolvaptan responder (HR 0.21; p = 0.02), and dosage of furosemide < 40 mg/day (HR 0.17; p = 0.01) were factors that were independently associated with the OS. The multivariate analysis revealed that C-reactive protein < 0.9 mg/dL (HR 0.07; p = 0.001), and furosemide dosage < 40 mg/day (HR 0.09; p = 0.003) were independently associated with the tolvaptan response. Conclusion: Therapeutic response to tolvaptan was associated with longer survival in cirrhosis patients complicated with ascites. These preliminary findings warrant validation and further exploration.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Positive Response to Tolvaptan Treatment Would Be a Good Prognostic Factor for Cirrhotic Patients with Ascites

Kida¹

2019

Dig Dis

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“…On the contrary, loop diuretics and spironolactone become less effective as liver cirrhosis advances and increasing doses are needed to be administered in order to achieve adequate diuretic response. 45 No predictive value was proposed by the existing evidence for baseline urine osmolality or 24-h urine sodium excretion. As a result, it can be assumed that high diuretic doses may diminish the effectiveness of tolvaptan by reducing renal perfusion and down-regulating the expression of aquaporin-2.…”

Section: Discussionmentioning

confidence: 99%

“…31 In addition, hepatitis C was linked to tolvaptan response, although the exact etiology of this observation remains unclear; it can be assumed that in contrast to hepatitis C-infected patients, alcohol-related cirrhosis is associated with higher rates of delays in treatment initiation and with intravascular volume depletion, which both may limit the effectiveness of tolvaptan. 45 No predictive value was proposed by the existing evidence for baseline urine osmolality or 24-h urine sodium excretion. However, because tolvaptan exerts its action by binding to V 2 receptors and inhibiting the reabsorption of free water, urine osmolality 4 h after its administration has been reported to be significantly lower in tolvaptan responders.…”

Section: Discussionmentioning

confidence: 99%

Predictors of tolvaptan short‐term response in patients with refractory ascites: A meta‐analysis

Bellos

Kontzoglou

Perrea

2019

J of Gastro and Hepatol

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Background and Aim Tolvaptan represents an oral V2‐receptor antagonist, which has been suggested as a promising add‐on diuretic treatment for refractory ascites. The present meta‐analysis aims to accumulate current evidence and identify which clinical and laboratory factors are linked to short‐term response to tolvaptan therapy. Methods Medline, Scopus, Cochrane Central Register of Controlled Trials, http://Clinicaltrials.gov, and Google Scholar databases were searched from inception. All observational studies reporting the correlation of patients' characteristics with tolvaptan response were selected. Results Tolvaptan response was associated with significantly higher baseline body weight (mean difference: 4.59 kg, 95% confidence interval [CI]: [3.58, 5.61]), presence of hepatitis C (odds ratio: 1.59 95% CI: [1.18, 2.14]), lower blood urea nitrogen (BUN) (mean difference: −6.88 mg/dL, 95% CI: [−8.13, −5.63]), lower serum creatinine (mean difference: −0.17 mg/dL, 95% CI: [−0.30, −0.05]), lower C‐reactive protein (mean difference: −1.43 mg/dL, 95% CI: [−2.52, −0.35]), and higher sodium levels (mean difference: 1.00 mEq/L, 95% CI: [0.45, 1.55]). The outcomes of bodyweight, hepatitis C, BUN, and C‐reactive protein remain significant independently of response definition and risk of bias. Conclusions The present findings suggest bodyweight, BUN, C‐reactive protein, and hepatitis C as potential predictive factors of tolvaptan short‐term response in patients with refractory ascites. Future studies are needed to introduce cut‐off values and construct an optimal combined screening model.

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“…Nine studies [19][20][21][22][23][24][25][26][27] were included in the analysis, with a total of 736 patients. Among them, 451 patients presented clinical response to tolvaptan therapy, while the rest 285 were judged as nonresponders.…”

Section: Included Studiesmentioning

confidence: 99%

Tolvaptan Response Improves Overall Survival in Patients with Refractory Ascites: A Meta-Analysis

Bellos¹,

Kontzoglou²,

Psyrri³

et al. 2019

Dig Dis

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Background and Aims: Refractory ascites represents a significant complication of decompensated cirrhosis, associated with increased mortality rates. The aim of this meta-analysis was to evaluate whether response to treatment with tolvaptan is associated with improved overall survival in cirrhotic patients with refractory ascites. Methods: Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception to April 11, 2019. All studies that assessed the overall survival of patients with ascites depending on their response to tolvaptan were held eligible. Results: Nine studies were included, with a total of 736 patients with cirrhosis and ascites. Response to tolvaptan was estimated to be linked to significantly improved overall survival (hazard ratio [HR] 0.42, 95% CI [0.31-0.58]). Subgroup analysis indicated that the same outcome was present when tolvaptan responsiveness was defined either as effective body weight loss (HR 0.44, 95% CI [0.30-0.63] or as effective sodium restoration (HR 0.35,]. Sensitivity analysis suggested that the presence of hepatocellular carcinoma, the sample size, and the quality of the studies did not significantly affect the overall result of the meta-analysis. Conclusions:The outcomes of the meta-analysis support the prognostic role of tolvaptan response in patients with cirrhosis and refractory ascites, as it was shown to lead to significantly improved overall survival. These findings should be confirmed by future large-scale studies, while efficient biomarkers should be identified in order to accurately predict response to tolvaptan and discriminate patients that would benefit from its administration.

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Tolvaptan is effective in treating patients with refractory ascites due to cirrhosis

Cited by 11 publications

References 21 publications

Positive Response to Tolvaptan Treatment Would Be a Good Prognostic Factor for Cirrhotic Patients with Ascites

Positive Response to Tolvaptan Treatment Would Be a Good Prognostic Factor for Cirrhotic Patients with Ascites

Predictors of tolvaptan short‐term response in patients with refractory ascites: A meta‐analysis

Tolvaptan Response Improves Overall Survival in Patients with Refractory Ascites: A Meta-Analysis

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