Abstract
BackgroundPrognostic 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.MethodsIn 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.ResultsSixteen 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 (ÎICWBIA%-6 h), significantly discriminated responders from non-responders (AUC = 0.97, P < 0.0001). ÎICWBIA%-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 ICWBIA. A rapid and early decrease of ICWBIA in response to tolvaptan was also predictive of a better transplant-free survival.ConclusionsBIA-defined water compartment monitoring may help predict short-term efficacy and survival in decompensated cirrhotic patients treated with tolvaptan.
Highlights
Prognostic value or clinical implications of fluid status monitoring in liver cirrhosis are not fully elucidated
bioimpedance analysis (BIA) has been showed to be an adequate tool for evaluation of total body water (TBW) and extracellular water (ECW) in cirrhotic patients with ascites, [6, 7] and has been reported to assess body cell mass (BCM) after trans-jugular intrahepatic porto-systemic shunt (TIPS) in liver cirrhosis [8]
It is note-worthy that the main purpose of this study is to find out the usefulness of fluid status monitoring after vasopressin 2 (V2) antagonism in cirrhotic patients, rather than to prove the usefulness of a V2 antagonist itself, since a previous study [18] has proved this point
Summary
Prognostic value or clinical implications of fluid status monitoring in liver cirrhosis are not fully elucidated. Malnutrition, systemic inflammation, and exaggerated activation of the renin-angiotensin-aldosterone system (RAAS) [10] play roles in the pathogenesis of cirrhotic ascites These factors are common pathophysiological features of fluid control in hemodialysis patients due to chronic renal failure. Body composition and fluid status monitoring assessed by non-invasive BIA, especially intracellular water (ICW), have been shown to be of prognostic value in acute decompensated heart failure, [11] acute kidney injury under continuous hemodiafiltration, [12] and patients with chronic renal failure under hemodialysis [13, 14]. In decompensated liver cirrhosis, the prognostic value and clinical implications of fluid status monitoring are not fully elucidated.
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