Predictive parameter of tolvaptan effectiveness in cirrhotic ascites

Kawaratani, Hideto; Fukui, Hiroshi; Moriya, Kyoji; Noguchi, Ryuichi; Namisaki, Tadashi; Uejima, Masakazu; Kitade, Mitsuteru; Takeda, Kosuke; Okada, Yasushi; Kaji, Kosuke; Nishimura, Norihisa; Takaya, Hiroaki; Aihara, Yousuke; Sawada, Yasuhiko; Sato, Shinya; Seki, Kazuhiko; Mitoro, Akira; Yamao, Junichi; Yoshiji, Hitoshi

doi:10.1111/hepr.12826

Cited by 30 publications

(46 citation statements)

References 33 publications

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“…The median duration of tolvaptan administration was 36 days (range 1–1,050 days). Median body weight change 1 week after tolvaptan treatment was –1.95 kg (range 1.1 to –8.5 kg), with 37 (50%) of these patients defined as responders, showing a body weight decrease ≥2 kg/week, a finding compatible with the results of earlier studies [13, 14, 19, 21]. Regarding adverse events, hypernatremia grade 1 was found in 2 patients (2 of 74, 2.7%), thirst was found in 8 patients (8 of 74, 10.8%), and hepatic encephalopathy was found in 7 patients (7 of 74, 9.5%), those compatible with a large scale prospective post-marketing surveillance study [19].…”

Section: Resultssupporting

confidence: 89%

Survival Benefit of Tolvaptan for Refractory Ascites in Patients with Advanced Cirrhosis

Tajiri

Tokimitsu²,

Ito

et al. 2018

Dig Dis

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Aims: The study aimed to evaluate the effects of tolvaptan treatment on survival of patients with decompensated liver cirrhosis with refractory ascites. Methods: This multicenter, retrospective, observational study included patients with cirrhosis who were treated with tolvaptan for hepatic ascites refractory to conventional diuretics. Patients who could and could not decrease accompanying diuretics within 1 month after tolvaptan administration were defined as the “Decreased” and “Not-decreased” groups, respectively. Results: Median body weight change 1 week after tolvaptan treatment was –1.95 kg, with the 50% of patients experiencing a 2 kg/week reduction. Spot urinary sodium was found to be a better predictor of tolvaptan response than liver function and liver fibrosis markers. Median survival was significantly longer (not reached versus 116 days, p = 0.005) and serum creatinine concentrations 12 weeks after tolvaptan administration significantly lower (0.99 vs. 1.55 mg/dL, p < 0.05) in the Decreased than in the Not-decreased group. Multivariate analysis showed that the presence of viable hepatocellular carcinoma (hazards ratio [HR] 2.14, p = 0.02) and a decrease in diuretics were independently prognostic of survival (HR 0.36, p < 0.01). Conclusions: The maintenance of renal function is essential in enhancing survival of patients with cirrhosis. Doses of diuretics should be adjusted appropriately during tolvaptan treatment.

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Section: Resultssupporting

confidence: 89%

Survival Benefit of Tolvaptan for Refractory Ascites in Patients with Advanced Cirrhosis

Tajiri

Tokimitsu²,

Ito

et al. 2018

Dig Dis

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“…The present meta-analysis was based on 17 studies, [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] involving 1362 cirrhotic patients. The present meta-analysis was based on 17 studies, [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] involving 1362 cirrhotic patients.…”

Section: Resultsmentioning

confidence: 99%

“…30 In this context, BUN-to-creatinine ratio has been also proposed as a specific marker, because its values inversely correlated with tolvaptan responsiveness. More specifically, the strongest associations were observed for baseline bodyweight and for BUN indicating that impaired renal function may impede the pharmacological action of tolvaptan.…”

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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“…Therefore, it is very important to predicte the therapeutic response to tolvaptan in clinical practice. Several recent clinical studies showed that serum BUN/Cr ratio ≥ 17.5, urine Na/K ratio < 3.09, and decreased urinary aquaporin 2 levels were predictive of being non-responsiveness to tolvaptan [21–23]. It is not totally clear why a short tolvaptan administration can improve survival in cirrhotic patients.…”

Section: Discussionmentioning

confidence: 99%

Tolvaptan treatment improves survival of cirrhotic patients with ascites and hyponatremia

et al. 2018

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BackgroundAlthough tolvaptan treatment improves hyponatremia, only few studies have investigated whether tolvaptan actually benefits the survival of cirrhotic patients. This study evaluated the impact of tolvaptan on six-month survival of decompensated cirrhotic patients with and without hyponatremia.MethodsTwo hundred forty-nine decompensated cirrhotic patients with or without hyponatremia were enrolled in a multicenter cohort study. Patients were divided into two groups according to receiving either tolvaptan or placebo treatment for 7-day. Subsequently, the patients were followed up for 6 months.ResultsTwo hundred thirty patients, including 98 with hyponatremia (tolvaptan vs. placebo: 69 vs. 29) finished the study. Tolvaptan did not alter serum sodium levels and survival outcome of decompensated cirrhotic patients without hyponatremia. However, tolvaptan treatment remarkably improved serum sodium levels and six-month survival in patients with hyponatremia. Following tolvaptan treatment, serum sodium levels were restored to normal in 63.8% of patients, whereas in patients receiving placebo, only 36.2% showed the same effect (P < 0.05). Compared to a six-month survival rate of 68.97% in patients receiving placebo, the survival rate in tolvapatan-treated patients was 89.94% (P < 0.05). Furthermore, six-month survival rate in the tolvaptan-treated hyponatremia patients with resolved serum sodium was 81.32%, whereas the survival in those with unresolved serum sodium was only 24% (P < 0.05).ConclusionsTolvaptan improves short term survival in most decompensated cirrhotic hyponatremia patients with resolved serum sodium.Trials registrationClinical trial one: ClinicalTrials.gov ID:NCT00664014, Registered on April 14, 2008.Clinical trial two: ClinicalTrials.gov ID:NCT01349335, Registered on March 5, 2010.Clinical trial three: ClinicalTrials.gov ID:NCT01349348, Registered on May 4, 2011.

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Predictive parameter of tolvaptan effectiveness in cirrhotic ascites

Abstract: Tolvaptan is useful and safe for the treatment of cirrhotic ascites. This report showed that BUN will predict the response of tolvaptan even when measured before tolvaptan treatment.

Cited by 30 publications

References 33 publications

Survival Benefit of Tolvaptan for Refractory Ascites in Patients with Advanced Cirrhosis

Survival Benefit of Tolvaptan for Refractory Ascites in Patients with Advanced Cirrhosis

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

Tolvaptan treatment improves survival of cirrhotic patients with ascites and hyponatremia

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