Alvarado-Tapias Edilmar, Ardevol Alba, Garcia-Guix Marta, Montañés Rosa, Pavel Oana, Cuyas Berta, Graupera Isabel, Brujats Anna, Vilades David, Colomo Alan, Poca Maria, Torras Xavier, Guarner Carlos, Concepción Mar, Aracil Carles, Torres Ferran, Villanueva Càndid
Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain.
Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain.
J Hepatol. 2020 Oct;73(4):829-841. doi: 10.1016/j.jhep.2020.03.048. Epub 2020 Apr 13.
BACKGROUND & AIMS: Whether the effect of β-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure in advanced cirrhosis is controversial. Herein, we aimed to evaluate the systemic and splanchnic hemodynamic effects of β-blockers in decompensated vs. compensated cirrhosis and to investigate the influence of systemic hemodynamic changes on survival times in decompensated cirrhosis.
Patients with cirrhosis and high-risk esophageal varices, without previous bleeding, were consecutively included and grouped according to the presence or absence of decompensation (ascites with or without overt encephalopathy). Systemic and hepatic hemodynamic measurements were performed before starting β-blockers and again after 1 to 3 months of treatment (short-term).
Four hundred and three patients were included (190 decompensated and 213 compensated). At baseline, decompensated patients had higher portal pressure than compensated patients and were more hyperdynamic, with higher cardiac output (CO) and lower arterial pressure. Under β-blockers, decompensated patients had lower portal pressure decrease (10 ± 18% vs. 15 ± 12%; p <0.05) and had greater reductions in heart rate (p <0.001) and CO (17 ± 15% vs. 10 ± 21%; p <0.01). Among patients with decompensated cirrhosis, those who died had a greater decrease in CO with β-blockers than survivors (21 ± 14% vs. 15 ± 16%; p <0.05) and CO under β-blockers independently predicted death by competing-risk regression analysis, with good diagnostic accuracy (C-index 0.74; 95% CI 0.66-0.83). Death risk was higher in decompensated patients with CO <5 L/min vs. CO ≥5 L/min (subdistribution hazard ratio 0.44; 95% CI 0.25-0.77; p = 0.004).
In patients with high-risk varices treated to prevent first bleeding, the systemic hemodynamic response to β-blockers is greater and the portal pressure decrease is smaller in those with decompensated cirrhosis. The short-term effect of β-blockers on CO might adversely influence survival in decompensated cirrhosis.
β-blockers are often used to reduce the risk of variceal bleeding in patients with cirrhosis. However, it is not known whether the effect of β-blockers on arterial pressure and/or cardiac function may offset the benefit of reducing portal pressure. Herein, we show that in patients with decompensated cirrhosis the potentially detrimental systemic effects of β-blockers are greater than in compensated patients, while the beneficial pressure lowering effects are reduced. The short-term effect of β-blockers on cardiac output may adversely influence survival in patients with decompensated cirrhosis.
β受体阻滞剂对动脉血压和/或心功能的影响是否会抵消其在晚期肝硬化中降低门静脉压力的益处,这一问题存在争议。在此,我们旨在评估β受体阻滞剂在失代偿期与代偿期肝硬化患者中的全身和内脏血流动力学效应,并研究全身血流动力学变化对失代偿期肝硬化患者生存时间的影响。
连续纳入患有肝硬化且有高危食管静脉曲张、既往未出血的患者,并根据是否存在失代偿(有或无明显肝性脑病的腹水)进行分组。在开始使用β受体阻滞剂之前以及治疗1至3个月后(短期)再次进行全身和肝脏血流动力学测量。
共纳入403例患者(190例失代偿期患者和213例代偿期患者)。基线时,失代偿期患者的门静脉压力高于代偿期患者,且血流动力学更为亢进,心输出量(CO)更高而动脉血压更低。在使用β受体阻滞剂治疗后,失代偿期患者的门静脉压力降低幅度较小(10±18%对15±12%;p<0.05),心率(p<0.001)和CO的降低幅度更大(17±15%对10±21%;p<0.01)。在失代偿期肝硬化患者中,死亡患者使用β受体阻滞剂后CO的降低幅度大于存活患者(21±14%对15±16%;p<0.05),且通过竞争风险回归分析,使用β受体阻滞剂后的CO独立预测死亡,诊断准确性良好(C指数0.74;95%CI 0.66 - 0.83)。CO<5 L/min的失代偿期患者的死亡风险高于CO≥5 L/min的患者(亚分布风险比0.44;95%CI 0.25 - 0.77;p = 0.004)。
在接受治疗以预防首次出血的高危静脉曲张患者中,失代偿期肝硬化患者对β受体阻滞剂的全身血流动力学反应更大,而门静脉压力降低幅度更小。β受体阻滞剂对CO的短期影响可能会对失代偿期肝硬化患者的生存产生不利影响。
β受体阻滞剂常用于降低肝硬化患者静脉曲张出血的风险。然而,尚不清楚β受体阻滞剂对动脉血压和/或心功能的影响是否会抵消降低门静脉压力的益处。在此,我们表明,在失代偿期肝硬化患者中,β受体阻滞剂潜在的有害全身效应大于代偿期患者,而有益的降压效应则降低。β受体阻滞剂对心输出量的短期影响可能会对失代偿期肝硬化患者的生存产生不利影响。