Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Department of Gastroenterology and Hepatology, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa City, Chiba, 272-8513, Japan.
BMC Gastroenterol. 2020 Mar 5;20(1):53. doi: 10.1186/s12876-020-01205-2.
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%-6 h), significantly discriminated responders from non-responders (AUC = 0.97, P < 0.0001). ΔICW%-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. A rapid and early decrease of ICW 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.
在肝硬化中,液体状态监测的预后价值或临床意义尚未完全阐明。托伐普坦是一种可口服的、选择性的血管加压素 V2 受体拮抗剂,已被批准用于美国和欧盟的低钠血症。在日本,它也以相对较低的剂量(3.75mg 至 7.5mg)用于肝硬化腹水,通过排泄无电解质的水发挥其利尿作用。我们假设生物阻抗定义的液体状态动态变化可以预测 V2 拮抗剂反应和肝硬化患者的生存情况。
在这项前瞻性观察性研究中,纳入了 30 名对常规利尿剂无反应的失代偿期肝硬化患者。使用非侵入性生物阻抗分析(BIA)设备评估身体成分的详细系列变化,并在 5 个时间点进行生化研究监测。
16 名患者被归类为短期应答者(53%)。BIA 定义的细胞内水的快速和早期减少,在首次剂量后 6 小时即可观察到(ΔICW%-6h),可显著区分应答者和无应答者(AUC=0.97,P<0.0001)。ΔICW%-6h 与 BIA 衍生的躯干相位角的变化高度相关,例如,在首次服用托伐普坦 24 小时后,降低身体电抗操作在 50kHz。基线血尿素氮和血清醛固酮较低预测了 ICW 的快速和早期减少。托伐普坦治疗后 ICW 的快速和早期减少也预测了更好的无移植生存。
BIA 定义的水室监测可能有助于预测接受托伐普坦治疗的失代偿性肝硬化患者的短期疗效和生存。