托伐普坦治疗顽固性腹水疗效及安全性分析

Efficacy and safety of tolvaptan in the treatment of patients with refractory ascites

目的：观察高度选择性血管加压素V2受体拮抗剂托伐普坦治疗顽固性腹水的疗效和安全性。方法在39例终末期肝病（20例肝硬化、19例肝硬化合并肝癌）引起的顽固性腹水患者，常规给予利尿剂（呋塞米80 mg/d；螺内酯160 mg/d）及白蛋白治疗的基础上，给予托伐普坦15 mg/d口服，治疗5～14 d。观察尿量、腹水消退、双下肢水肿改善及血清钠和肝功能变化情况。结果在托伐普坦治疗结束后24 h，患者平均尿量为（3533.3±154.65）ml/d，明显高于治疗前（1851.3±167.12） ml/d（P〈0.01）；82.5%（32/39）患者腹水改善，2例I型肝肾综合征患者对托伐普坦治疗无明显效果；在21例低钠血症患者中，血清钠较治疗前[（128.1±4.25） mmol/L]明显上升[（132.9±4.1） mmol/l，P〈0.01]；治疗前后患者MELD评分[（37.5±5.6）对（38.1±5.7）]、血钾水平[（4.1±0.5） mmol/L对（4.2±0.6） mmol/L]无明显变化；该药的不良反应以口干、口渴为主，发生率为15.4%。结论托伐普坦对终末期肝病引起的顽固性腹水患者有一定的利尿作用，可同时纠正低钠血症，短期应用托伐普坦对肝功能无明显影响。

Objective To observe the efficacy and safety of highly selective vasopressin V2 receptor antagonist tolvaptan in the treatment of patients with refractory ascites. Methods Thirty-nine patients with end-stage liver diseases and refractory ascites（20 patients with cirrhosis and 19 patients with hepatocellular carcinoma） were enrolled in this study. In additional to conventional diuretics（furosemide 80 mg/d and spironolactone 160 mg/d） and albumin therapy,the patients received tolvaptan orally at dose of 15 mg/d for 5 to 14 days. The urine amount,ascites,lower extremity edema,serum sodium and liver function tests were observed. Results The average urine amount per day after tolvaptan treatment was [（3533.3 ±154.65）ml/d],significantly higher than the baseline [（1851.3±167.12） ml/d,P〈0.01];Ascites was improved in 82.5%（32/39） of all patients,and in 84.2% of cirrhotic patients with hepatocellular carcinoma,but only in 77.8% of cirrhotic patients with hepatorenal syndrome;Two patients with hepatorenal syndrome type I were not responsive to tolvaptan treatment;The serum sodium levels increased to [（132.9±4.1） mmol/l] after treatment,significantly higher than in pre-treatment [（128.1±4.25） mmol/L,P〈0.01] in 21 patients with hyponatremia;MELD scores and serum potassium before treatment were （37.5±5.6） and（4.1±0.5） mmol/L,respectively,which were not improved after tolvaptan treatment [（38.1±5.7） and （4.2±0.6） mmol/L,respectively];Dry mouth and thirst were the main adverse effects in the patients receiving tolvaptan and the occurrence rate was 15.4%. Conclusions Tolvaptan is effective in correcting hyponatremia in patients with end-stage liver diseases and refractory ascites,without adverse effect on liver functions as a short-term application.