Long-Term Administration and Outcomes of Tolvaptan for Hepatic Edema

Abstract

Objective: Tolvaptan is an oral vasopressin V2 receptor antagonist that became available as therapy for decompensated hepatic cirrhosis-induced ascites in 2013. It has now been more than 3 years since hepatic edema was included in the indication. We investigated use of tolvaptan in our department, including long-term administration, discontinuation, and re-administration after discontinuation. Methods: The subjects were 62 patients with hepatic edema treated with tolvaptan between september 2013 and december 2016. Physical parameters and blood data during hospitalization and the course thereafter were investigated retrospectively. Results: The median age was 71.2 (49-87) years old, the mean Child-Pugh score was 9.5 ± 1.7, background liver Hepatitis C virus /Hepatitis B virus/Alcohol/Non-alcoholic steatohepatitis/Others=38/5/6/5/8, and 41 patients were complicated by hepatocellular carcinoma. Tolvaptan was initiated at 3.75 mg in all patients, and the dose was increased to 7.5 mg if the effect was insufficient after administration for 3 days. Patients who lost ≥ 1.5 kg weight after tolvaptan administration for one week were defined as early responders (39/62, 62.9%). The median duration of tolvaptan administration was 96 (7-992) days. Tolvaptan was continued in 46 patients at the outpatient clinic. In 5 patients, tolvaptan was discontinued because ascites improved, but 3 required readministration. Of the 46 patients who received continuous tolvaptan, 18 died, but 14 did not require removal of ascites by puncture or Cell−free and Concentrated Ascites Reinfusion Therapy before death. In an analysis of outcomes by Log-rank test, there was no significant relationship with Child-Pugh score or Model for End-Stage Liver Disease score, but significant effects of hepatocellular carcinoma and continuous tolvaptan. In multivariate analysis using Cox proportional hazards regression analysis, hepatocellular carcinoma (hazard ratio 3.366) and continuous tolvaptan (hazard ratio 7.291) were identified as significant independent factors related to outcome. Conclusion: Continuous administration of tolvaptan may enable long-term control of hepatic edema and improve the outcome of patients with hepatic cirrhosis.