Abraldes Juan G, Albillos Agustin, Bañares Rafael, Turnes Juan, González Rosario, García-Pagán Juan Carlos, Bosch Jaime
Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Spain.
Gastroenterology. 2009 May;136(5):1651-8. doi: 10.1053/j.gastro.2009.01.043. Epub 2009 Jan 24.
BACKGROUND & AIMS: Simvastatin improves liver generation of nitric oxide and hepatic endothelial dysfunction in patients with cirrhosis, so it could be an effective therapy for portal hypertension. This randomized controlled trial evaluated the effects of continuous simvastatin administration on the hepatic venous pressure gradient (HVPG) and its safety in patients with cirrhosis and portal hypertension.
Fifty-nine patients with cirrhosis and portal hypertension (HVPG > or =12 mm Hg) were randomized to groups that were given simvastatin 20 mg/day for 1 month (increased to 40 mg/day at day 15) or placebo in a double-blind clinical trial. Randomization was stratified according to whether the patient was being treated with beta-adrenergic blockers. We studied splanchnic and systemic hemodynamics and variables of liver function and safety before and after 1 month of treatment.
Simvastatin significantly decreased HVPG (-8.3%) without deleterious effects in systemic hemodynamics. HVPG decreases were observed in patients who were receiving beta-adrenergic blockers (-11.0%; P = .033) and in those who were not (-5.9%; P = .013). Simvastatin improved hepatic, fractional, and intrinsic clearance of indocyanine green, showing an improvement in effective liver perfusion and function. No significant changes in HVPG and liver function were observed in patients receiving placebo. The number of patients with adverse events did not differ significantly between groups. No patient was withdrawn from the study based on adverse events.
Simvastatin decreased HVPG and improved liver perfusion in patients with cirrhosis. These effects were additive with those of beta-adrenergic blockers. The beneficial effects of simvastatin should be confirmed in long-term clinical trials for portal hypertension.
辛伐他汀可改善肝硬化患者肝脏一氧化氮的生成及肝内皮功能障碍，因此可能是治疗门静脉高压的有效疗法。本随机对照试验评估了持续给予辛伐他汀对肝硬化门静脉高压患者肝静脉压力梯度（HVPG）的影响及其安全性。
59例肝硬化门静脉高压患者（HVPG≥12 mmHg）在一项双盲临床试验中被随机分为两组，一组给予辛伐他汀20 mg/天，持续1个月（第15天增至40 mg/天），另一组给予安慰剂。随机分组根据患者是否正在接受β-肾上腺素能阻滞剂治疗进行分层。我们在治疗1个月前后研究了内脏和全身血流动力学以及肝功能和安全性变量。
辛伐他汀显著降低了HVPG（-8.3%），且对全身血流动力学无有害影响。接受β-肾上腺素能阻滞剂治疗的患者HVPG降低（-11.0%；P = 0.033），未接受该治疗的患者HVPG也降低（-5.9%；P = 0.013）。辛伐他汀改善了肝脏对吲哚菁绿的清除率、分数清除率和固有清除率，表明有效肝脏灌注和功能有所改善。接受安慰剂的患者HVPG和肝功能无显著变化。两组间不良事件患者数量无显著差异。没有患者因不良事件退出研究。
辛伐他汀降低了肝硬化患者的HVPG并改善了肝脏灌注。这些作用与β-肾上腺素能阻滞剂的作用相加。辛伐他汀的有益作用应在门静脉高压的长期临床试验中得到证实。
