Response to tolvaptan and its effect on prognosis in cirrhotic patients with ascites

Kogiso, Tomomi; Yamamoto, Kaori; Kobayashi, Mutsuki; Ikarashi, Yuichi; Kodama, Kazuhisa; Taniai, Makiko; Torii, Nobuyuki; Hashimoto, Etsuko; Tokushige, Katsutoshi

doi:10.1111/hepr.12822

Cited by 25 publications

(41 citation statements)

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“…The dose of tolvaptan was consistent at 7.5 mg per day in the current study. In prior studies with a starting dose of tolvaptan of 3.75 mg daily, weight reduction within one week ranged from 1.5-3.8 kg (8)(9)(10)(11)13). The mean weight reduction at one week was 3.4±2.9 kg in the present study.…”

Section: Discussionsupporting

confidence: 42%

“…Response to tolvaptan was associated with improved survival in the current study. Previous studies have reported similar results from univariate analyses (8,9). As aforementioned, renal function and serum Na level may be considered as major indicators of tolvaptan responsiveness, particularly as these are established prognostic factors in patients with cirrhosis (7).…”

Section: Univariate Analysis Multivariate Analysis ------------------mentioning

confidence: 64%

“…Additionally, response to tolvaptan was associated with improved long-term outcomes in cirrhotic patients with refractory ascites. The short-term effects of tolvaptan in patients with refractory ascites due to cirrhosis have been reported (8)(9)(10)(11)(12)(13). As the starting doses in previous studies were 3.75 mg with dose escalation up to 7.5 mg within one week, tolvaptan doses in these studies were heterogeneous.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, hyponatremia has been documented to be an independent predictor for poor prognosis in patients with cirrhosis (7), and is observed in ~half of cirrhotic individuals (15). Recent studies have also reported that low serum creatinine is a predictor of response to tolvaptan in the short-term in univariate analyses (8,9). Deterioration of renal function in patients with cirrhosis directly influences their prognosis (7).…”

Section: Univariate Analysis Multivariate Analysis ------------------mentioning

confidence: 99%

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

et al. 2017

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Abstract. The treatment of refractory ascites due to cirrhosis is a clinical challenge for hepatologists. Tolvaptan, a novel aquaporin modulator, was made available in Japan in 2013 for the treatment of patients with refractory ascites due to cirrhosis. Despite the potential of this drug, few reports are available regarding its clinical use. The aim of the present study was to clarify the efficacy of tolvaptan in patients with refractory ascites due to cirrhosis and to review the clinical outcomes of treatment. Medical records were retrospectively reviewed for 65 patients with refractory ascites due to cirrhosis who were treated daily with 7.5 mg tolvaptan. The median follow-up time, defined as the period between starting tolvaptan and the last clinic visit or date of mortality, was 175 days (interquartile range 56-406). After one week of tolvaptan treatment, the mean weight reduction was 3.4 kg, with a response rate of 69% (45/65). Subsequently, factors associated with the response to tolvaptan were analyzed. On univariate analysis, maintaining serum sodium (Na) ≥140 mEq/l and an estimated glomerular filtration rate (eGFR) ≥55 ml/min were significant predictors of response (P<0.05). On multivariate analysis, hepatitis C virus etiology, maintaining serum Na ≥140 mEq/l and an eGFR ≥55 ml/min were significant predictors of response (P<0.05). Factors associated with survival were also analyzed using the Cox proportional hazard model. On multivariate analysis, responsiveness to tolvaptan was a predictor of long-term survival (P=0.002), and hyperbilirubinemia was associated with short-term survival (P=0.028). Additionally, KaplanMeier analysis with a log-rank test indicated longer survival times in tolvaptan responders than non-responders (P=0.011).In conclusion, tolvaptan was effective in treating patients with refractory ascites due to cirrhosis. In particular, tolvaptan treatment was highly effective for patients with hepatitis C virus etiology and normal serum Na and renal function. Furthermore, response to tolvaptan was associated with longer survival time while hyperbilirubinemia was associated with shorter survival time.

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Section: Discussionsupporting

confidence: 42%

Section: Univariate Analysis Multivariate Analysis ------------------mentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Univariate Analysis Multivariate Analysis ------------------mentioning

confidence: 99%

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

et al. 2017

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“…3258-R). The results of this study, including figures and tables, were published in Hepatology Research [13] and were transferred with permission.…”

Section: Methodsmentioning

confidence: 99%

Predictors of the Response to Tolvaptan Therapy and Its Effect on Prognosis in Cirrhotic Patients with Ascites

Kogiso¹,

Yamamoto²,

Kobayashi³

et al. 2017

Ascites - Physiopathology, Treatment, Complications and Prognosis

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Aims: The vasopressin V2 receptor antagonist, tolvaptan, has been reported to be effective in cirrhotic patients with ascites. Here, we evaluated predictors of the response to tolvaptan. Methods: A total of 97 patients with cirrhosis (60 males; median age, 63 years) who had been treated for ascites with oral tolvaptan were enrolled. Tolvaptan efficacy was defined as urine volume increase of ≥500 mL or a urine volume ≥2000 mL/day on the day following treatment. Normalization of the serum sodium (Na) level after 1 week of treatment and the posttreatment survival rate was analyzed. Results: Tolvaptan therapy resulted in effective urination in 67% of patients. A multivariate analysis revealed that the blood urea nitrogen/creatinine (BUN/Cr) ratio and urinary Na/potassium (Na/K) ratio were predictive of the tolvaptan response (p <0.05). The serum Na level was 135 (121-145) mEq/L, and normal levels were recovered in 50.0% of the patients with an initial Na level of <135 mEq/L. The posttreatment survival rate was significantly higher in patients who responded to tolvaptan therapy (p <0.05). Conclusions: The combination of the initial BUN/Cr and urine Na/K ratios and a normalized serum Na level after 1 week was predictive of a favorable outcome to tolvaptan therapy.

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Risk and protective factors of acute kidney injury in decompensated cirrhotic patients with ascites on tolvaptan

et al. 2021

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Background and AimAcute kidney injury (AKI) is a life‐threatening complication of liver cirrhosis. Here, we evaluated the risk factors and characteristics of AKI in cirrhosis.Patients/MethodsThis was a single‐center retrospective study. A total of 199 Japanese patients with decompensated liver cirrhosis (104 men, median age 61 years) were enrolled and received tolvaptan orally. Survival rates and new onset of AKI were monitored, and risk factors were evaluated.ResultsForty‐six patients (23.1%) suffered an AKI complication and exhibited significantly poorer survival (P < 0.01). The rates of hepatic encephalopathy (P < 0.01) and chronic kidney disease (CKD; P = 0.02) were significantly increased in patients with AKI. The rate of proton pump inhibitor (PPI)/H2 blocker treatment (P = 0.04) was significantly lower, whereas that of ascites drainage was significantly higher in the AKI cases (P < 0.01). The AKI risk was significantly increased in patients with hepatic encephalopathy (HR 4.18, 95% CI 1.618–10.771). In contrast, the incidence of AKI was significantly lower in patients with a higher serum albumin level (HR 0.36, 95% CI 0.142–0.914, P = 0.03). Treatment with PPI/H2 blockers (HR 0.30, 95% CI 0.126–0.711, P < 0.01) or kanamycin/rifaximin (HR 0.26, 95% CI 0.075–0.929, P = 0.04) was significantly associated with a reduced risk of AKI development.ConclusionsAKI incidence was increased in patients with decreased liver function and was associated with poor survival. PPI/H2 blocker or kanamycin/rifaximin treatment may reduce the risk of AKI.

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Response to tolvaptan and its effect on prognosis in cirrhotic patients with ascites

Abstract: Urinary BUN and Na excretion were predictive of a response to tolvaptan, and tolvaptan treatment may improve the prognosis of cirrhotic patients.

Cited by 25 publications

References 41 publications

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

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

Predictors of the Response to Tolvaptan Therapy and Its Effect on Prognosis in Cirrhotic Patients with Ascites

Risk and protective factors of acute kidney injury in decompensated cirrhotic patients with ascites on tolvaptan

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