Therapeutic effects of short- and intermediate-term tolvaptan administration for refractory ascites in patients with advanced liver cirrhosis.

Abstract

Tolvaptan, an oral arginine vasopressin V2 receptor antagonist, became available for hepatic ascites. We evaluated the therapeutic efficacy and safety of tolvaptan administration to treat refractory ascites. Data were collected from 15 hospitalized patients with cirrhosis (hepatitis C, 10; alcoholism, five) after adding tolvaptan (3.75-11.25 mg/day) to conventional diuretics. Bodyweights and serum sodium and creatinine concentrations were measured. Tolvaptan was continued for 4 weeks or longer for a median follow-up period of 42 days (range, 28-56). In the first week (introduction phase), tolvaptan significantly reduced median weight (66.6, 65.9 and 63.1 kg on days 0, 1 and 7, respectively; P < 0.004). The numbers of good responders (≥3 kg reduction in 4 days), responders (<3 kg weight reduction) and non-responders (no weight reduction) were seven (46.7%), six (40.0%) and two of the 15 (13.3%), respectively. The two non-responders had concomitant chylous pleural effusion or spontaneous bacterial peritonitis. All patients continued tolvaptan for 2 weeks or longer and six (40%, three good responders and three responders) were treated for a median of 42 days without additional intervention. During this intermediate-term administration of tolvaptan, the median weight reduction was statistically significant (65.4, 61.9 and 56.9 kg on days 0, 7 and 42, respectively; P < 0.030) and there was no serum sodium imbalance or renal dysfunction; but two of these six developed hepatic coma. Tolvaptan safely alleviated fluid retention caused by hepatic cirrhosis. Intermediate-term administration of tolvaptan apparently helped maintain weight reduction achieved during the introduction phase.