Dose‐finding trial of tolvaptan in liver cirrhosis patients with hepatic edema: A randomized, double‐blind, placebo‐controlled trial

Okita, Kiwamu; Kawazoe, Seiji; Hasebe, Chitomi; Kajimura, Kozo; Kaneko, Akira; Okada, Mitsuru; Sakaida, Isao

doi:10.1111/hepr.12099

Cited by 67 publications

(77 citation statements)

References 23 publications

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“…Among them, tolvaptan (7.5-30 mg/day for 7 days) showed add-on effects to conventional diuretics on ascites in multicenter RCTs for poor responders to the standard diuretic therapy (furosemide at 40 mg/day or greater and spironolactone at 25 mg/day or greater; or furosemide at 20 mg/day or greater and spironolactone at 50 mg/day or greater) [150,151]. As a dosage of 7.5 mg/day showed the maximum effects with preferable tolerability [151] and a dosage of 3.75 mg/day also exerted significant effects [152], the proper dosage was determined as 3.75-7.5 mg/day. The effects were unrelated to serum albumin levels [150].…”

Section: Cq: Is Albumin Infusion Effective For Treatment Of Cirrhoticmentioning

confidence: 99%

Evidence-based clinical practice guidelines for liver cirrhosis 2015

et al. 2016

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The Japanese Society of Gastroenterology revised the evidence-based clinical practice guidelines for liver cirrhosis in 2015. Eighty-three clinical questions were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases for the period between 1983 and June 2012. Manual searching of the latest important literature was added until August 2015. The guidelines were developed with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. This digest version in English introduces selected clinical questions and statements related to the management of liver cirrhosis and its complications. Branched-chain amino acids relieve hypoalbuminemia and hepatic encephalopathy and improve quality of life. Nucleoside analogues and peginterferon plus ribavirin combination therapy improve the prognosis of patients with hepatitis B virus related liver cirrhosis and hepatitis C related compensated liver cirrhosis, respectively, although the latter therapy may be replaced by direct-acting antivirals. For liver cirrhosis caused by primary biliary cirrhosis and active autoimmune hepatitis, urosodeoxycholic acid and steroid are recommended, respectively. The most adequate modalities for the management of variceal bleeding are the endoscopic injection sclerotherapy for esophageal varices and the balloon-occluded retrograde transvenous obliteration following endoscopic obturation with cyanoacrylate for gastric varices. Beta-blockers are useful for primary prophylaxis of esophageal variceal bleeding. The V 2 receptor antagonist tolvaptan is a useful add-on therapy in careful diuretic therapy for ascites. Albumin infusion is useful for the prevention of paracentesis-induced circulatory disturbance and renal failure. In addition to disaccharides, the nonabsorbable antibiotic rifaximin is useful for the management of encephalopathy. Anticoagulation therapy is proposed for patients with acute-onset or progressive portal vein thrombosis.

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Section: Cq: Is Albumin Infusion Effective For Treatment Of Cirrhoticmentioning

confidence: 99%

Evidence-based clinical practice guidelines for liver cirrhosis 2015

et al. 2016

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“…Although diuretics, such as loop diuretics, are the standard treatment for hepatic ascites, loop diuretics can induce renal dysfunction and hyponatremia [5, 6]. The vasopressin V2 receptor antagonist, tolvaptan, which was developed in Japan, was shown effective in 50–60% of cirrhotic patients with ascites refractory to conventional diuretics [7-9]. A meta-analysis also found that vasopressin V2 receptor antagonists improved hyponatremia and may improve symptoms in cirrhosis patients with refractory ascites [10].…”

Section: Introductionmentioning

confidence: 99%

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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“…Arginine vasopressin receptor antagonists, a novel class of diuretics, have been recently approved for the treatment of cirrhosis-related fluid retention in Japan (3,4). These diuretics antagonize vasopressin V2 receptors, resulting in the inhibition of electrolyte-free water reabsorption and an increase in electrolyte-free water excretion (5).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of peritoneovenous shunt for treating tolvaptan-resistant refractory ascites in a cirrhotic patient with portal vein thrombosis: A case report

et al. 2016

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Abstract. Peritoneovenous shunt is normally used for the treatment of refractory ascites. However, its efficacy in treating tolvaptan-resistant refractory ascites has not been reported thus far. In addition, the impact of peritoneovenous shunt on the prognosis of cirrhotic patients remains controversial. In the present report, a case of tolvaptan-resistant refractory ascites associated with liver cirrhosis and portal vein thrombosis is described. The male patient was diagnosed with hepatitis C virus-related liver cirrhosis at the age of 51 years. At the age of 56 years, the patient developed portal vein thrombosis, resulting in the development of refractory ascites. Since the ascites was resistant to treatment with a low-sodium diet and diuretics such as tolvaptan, a peritoneovenous shunt was implanted upon obtaining consent. The shunt immediately increased the urine volume, and the ascites was markedly decreased. The patient's body weight decreased from 62.7 to 57.1 kg in 2 days, and his ascites symptom inventory-7 score decreased from 23 to 0 points in 31 days. Although the patient succumbed to sepsis on day 486 following the shunt implant, his activities of daily living were preserved until 8 days prior to mortality. Thus, the present case supports the efficacy of peritoneovenous shunt for the treatment of tolvaptan-resistant refractory ascites associated with liver cirrhosis and portal vein thrombosis. Furthermore, the present case suggests that peritoneovenous shunt may prolong the survival of cirrhotic patents with refractory ascites. IntroductionAscites that does not resolve with standard medical treatment such a low-sodium diet and diuretics is known as refractory ascites, and is frequently associated with the development of hepatorenal syndrome, spontaneous bacterial peritonitis and dilutional hyponatremia (1). Refractory ascites also causes a loss of appetite and muscle wasting, and impairs the activities of daily living (ADL) (1). Thus, refractory ascites is a life-threatening complication that lowers the quality of life of cirrhotic patients, and is an independent predictor of short survival (1,2).One of the main reasons for cirrhosis-related water retention is a reduced ability of the kidneys to excrete electrolyte-free water, due to an increase in the levels of arginine vasopressin (3). Arginine vasopressin receptor antagonists, a novel class of diuretics, have been recently approved for the treatment of cirrhosis-related fluid retention in Japan (3,4). These diuretics antagonize vasopressin V2 receptors, resulting in the inhibition of electrolyte-free water reabsorption and an increase in electrolyte-free water excretion (5). Tolvaptan, a vasopressin V2 receptor antagonist, improves hepatic edema and reduces ascites in cirrhotic patients (6,7). However, tolvaptan may not always be effective for treating refractory ascites, since there are various mechanisms involved in the development of this condition (1,8).Peritoneovenous shunt was designed to transport ascites from the peritoneal cavity back in...

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Dose‐finding trial of tolvaptan in liver cirrhosis patients with hepatic edema: A randomized, double‐blind, placebo‐controlled trial

Abstract: Tolvaptan at 7.5 mg/day was considered the optimal dose in liver cirrhosis patients with hepatic edema who showed inadequate response to conventional diuretics.

Cited by 67 publications

References 23 publications

Evidence-based clinical practice guidelines for liver cirrhosis 2015

Evidence-based clinical practice guidelines for liver cirrhosis 2015

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

Efficacy of peritoneovenous shunt for treating tolvaptan-resistant refractory ascites in a cirrhotic patient with portal vein thrombosis: A case report

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