Clinical implications with tolvaptan on monitored bioimpedance-defined fluid status in patients with cirrhotic...

Prognostic value or clinical implications of fluid status monitoring in liver cirrhosis are not fully elucidated. Tolvaptan, an orally available, selective vasopressin V2-receptor antagonist approved for hyponatremia in the United States and European Union. It is also used for cirrhotic ascites at a relatively low dose (3.75 mg to 7.5 mg) in Japan, exerts its diuretic function by excreting electrolyte-free water. We hypothesized that bioimpedance-defined dynamic changes in fluid status allow prediction of response of V2 antagonism and survival in cirrhotic patients.

In this prospective observational study, 30 patients with decompensated liver cirrhosis who were unresponsive to conventional diuretics were enrolled. Detailed serial changes of body composition that were assessed by using non-invasive bioimpedance analysis (BIA) devices, along with biochemical studies, were monitored at 5 time points.

Sixteen patients were classified as short-term responders (53%). Rapid and early decrease of BIA-defined intracellular water, as soon as 6 h after the first dose (ΔICW_BIA%-6 h), significantly discriminated responders from non-responders (AUC = 0.97, P < 0.0001). ΔICW_BIA%-6 h was highly correlated with the change of BIA-derived phase angle of trunk, e.g. reduced body reactance operated at 50 kHz after 24 h of the first dose of tolvaptan. Lower baseline blood urea nitrogen and lower serum aldosterone were predictive of a rapid and early decrease of ICW_BIA. A rapid and early decrease of ICW_BIA in response to tolvaptan was also predictive of a better transplant-free survival.

BIA-defined water compartment monitoring may help predict short-term efficacy and survival in decompensated cirrhotic patients treated with tolvaptan.