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终末期肝病等待肝移植患者的选择性口服血管加压素 V2 受体拮抗剂:初步研究。

A selective oral vasopressin V2-receptor antagonist for patients with end-stage liver disease awaiting liver transplantation: a preliminary study.

机构信息

Hepato-Biliary-Pancreatic Surgery Division, and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo.

National Center for Global Health and Medicine.

出版信息

Biosci Trends. 2019 May 12;13(2):189-196. doi: 10.5582/bst.2019.01072. Epub 2019 Apr 24.

Abstract

Administration of the selective arginine vasopressin V2 receptor antagonist tolvaptan to cirrhotic patients is controversial. There are no reports of tolvaptan use for patients with far-advanced end-stage liver disease (ESLD) and refractory ascites awaiting liver transplantation. Between 2013 and 2016, 64 patients awaiting adult-to-adult living donor liver transplantation (LDLT) were screened for enrollment. Patients with refractory ascites and on dual conventional diuretics (≥ 50 mg/day of spironolactone and ≥ 20 mg/day of a loop diuretic) were enrolled and assigned to the tolvaptan (TOL) group (n = 10), and low-dose tolvaptan, 3.75 mg/day, was started. The remaining patients who had no or little ascites on conventional diuretic therapy (CDT) were assigned to the CDT group (n = 23). The median model for end-stage liver disease and Child-Pugh scores were 16 (range 7-41) and 10 (7-15), respectively. The median dose of spironolactone in the TOL group was 88 mg (range 50-200) vs. 50 (0-100) in the CDT group (p < 0.01). The median dose of loop diuretics in the TOL group was 70 mg (20-120) vs. 20 (0-80) in the CDT group (p = 0.03). No significant liver damage was detected during tolvaptan therapy. Tolvaptan demonstrated favorable effects in 60% (6/10) of the patients, decreasing the body weight by at least 1.5 kg during the 7 day treatment. These findings suggest that low-dose of tolvaptan may be safe for patients having far-advanced ESLD patients with apparent and refractory ascites taking dual conventional diuretics for a short period before LDLT.

摘要

在肝硬化患者中应用选择性精氨酸血管加压素 V2 受体拮抗剂托伐普坦存在争议。目前尚无托伐普坦用于终末期肝病(ESLD)和难治性腹水等待肝移植的患者的报告。2013 年至 2016 年间,对 64 例等待成人对成人活体供肝移植(LDLT)的患者进行了筛选,以确定是否入组。纳入难治性腹水且正在接受双常规利尿剂(螺内酯≥50mg/天和袢利尿剂≥20mg/天)治疗的患者,并将其分配至托伐普坦(TOL)组(n=10),起始给予托伐普坦 3.75mg/天。其余对常规利尿剂治疗(CDT)无或仅有少量腹水的患者被分配至 CDT 组(n=23)。中位终末期肝病模型和 Child-Pugh 评分分别为 16(范围 7-41)和 10(7-15)。TOL 组的螺内酯中位剂量为 88mg(范围 50-200),而 CDT 组为 50mg(范围 0-100)(p<0.01)。TOL 组的袢利尿剂中位剂量为 70mg(20-120),而 CDT 组为 20mg(0-80)(p=0.03)。托伐普坦治疗期间未发现明显的肝损伤。托伐普坦在 60%(6/10)的患者中显示出良好的效果,在 7 天的治疗期间体重至少减轻 1.5kg。这些发现表明,在 LDLT 前短期应用双常规利尿剂治疗的,明显且难治性腹水的远末期 ESLD 患者,低剂量托伐普坦可能是安全的。

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