β-受体阻滞剂治疗可能预防肝硬化进展

StephenW

SUMMARY AND COMMENT | GASTROENTEROLOGY

March 29, 2019

Beta-Blocker Therapy Might Prevent Cirrhosis Progression

Atif Zaman, MD, MPH reviewing Villanueva C et al. Lancet 2019 Mar 22

In patients with compensated cirrhosis and portal hypertension, beta-blocker use reduced decompensation risk but not mortality.

Clinically significant portal hypertension (CSPH; portal pressure ≥10 mmHg) is a key driver of hepatic decompensation (development of ascites, encephalopathy, or variceal hemorrhage) in patients with compensated cirrhosis. To determine whether reducing portal pressure in this high-risk group using beta-blocker therapy lowers decompensation and death rates, investigators in Spain conducted a randomized, controlled trial in 201 patients with compensated cirrhosis and CSPH.

Participants were divided into a beta-blocker–responsive group (135 patients; defined as those who had a ≥10% drop in hepatic venous pressure gradient from baseline when given a propranolol infusion challenge) and a beta-blocker–nonresponsive group (66 patients). The responsive group was randomized to receive either propranolol or placebo and the nonresponsive group to either carvedilol or placebo. The primary endpoint was incidence of decompensation or death.

During a median follow-up of 37 months, among the 100 patients who received beta-blockers, the rate of decompensation or death was significantly lower compared with the 101 patients who received placebo (16% vs. 27%; hazard ratio 0.51). This difference was attributable to a significantly lower incidence of ascites; rates of encephalopathy, hemorrhage, and mortality were similar between groups.
Comment

This study suggests a role for beta-blockers beyond variceal management. In the early phases of cirrhosis, it might reduce rates of hepatic decompensation, mainly via reduction of ascites. However, beta-blocker use did not confer a survival benefit over a median follow-up of 2.5 years, and therapy compliance may be difficult to maintain in clinical practice. Additional studies of longer duration are needed and should target potential high-risk populations to determine which subset of patients would most benefit from beta-blocker therapy.

Editor Disclosures at Time of Publication

Disclosures for Atif Zaman, MD, MPH at time of publication

Grant/Research Support
       

Merck

Citation(s):

Villanueva C et al. β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): A randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2019 Mar 22; [e-pub]. (https://doi.org/10.1016/S0140-6736(18)31875-0)

StephenW

摘要和评论|胃肠病

2019年3月29日

β-受体阻滞剂治疗可能预防肝硬化进展

Atif Zaman，MD，MPH审查了Villanueva C等人。柳叶刀2019年3月22日

在代偿性肝硬化和门静脉高压症患者中，β受体阻滞剂可降低失代偿风险但不降低死亡率。

临床上显着的门静脉高压症（CSPH;门静脉压力≥10mmHg）是代偿性肝硬化患者肝功能失代偿（腹水，脑病或静脉曲张出血的发生）的关键驱动因素。为了确定使用β受体阻滞剂治疗降低这一高风险组的门静脉压力是否会降低失代偿和死亡率，西班牙的研究人员对201名患有代偿性肝硬化和CSPH的患者进行了一项随机对照试验。

参与者被分为β受体阻滞剂反应组（135例患者;定义为给予普萘洛尔输注激发时从基线开始下降≥10％肝静脉压梯度的患者）和β受体阻滞剂无反应组（66例患者）响应组随机接受普萘洛尔或安慰剂和无反应组接受卡维地洛或安慰剂。主要终点是失代偿或死亡的发生率。

在37个月的中位随访期间，在接受β受体阻滞剂的100名患者中，与101名接受安慰剂的患者相比，失代偿或死亡率显着降低（16％对27％;风险比0.51）。这种差异可归因于腹水发生率显着降低;各组的脑病，出血和死亡率相似。
评论

该研究表明β受体阻滞剂在静脉曲张管理之外的作用。在肝硬化的早期阶段，它可能会降低肝功能失代偿的发生率，主要是通过减少腹水。然而，β受体阻滞剂的使用并未使中位随访2。5年的生存获益，并且在临床实践中可能难以维持治疗依从性。需要进行更长时间的其他研究，并且应针对潜在的高风险人群，以确定哪一部分患者最能从β受体阻滞剂治疗中获益。

出版时的编辑披露

Atif Zaman，MD，MPH在出版时的披露

拨款/研究支持


默克

引用（S）：

Villanueva C等。 β受体阻滞剂可预防临床显着门静脉高压症患者肝硬化失代偿（PREDESCI）：一项随机，双盲，安慰剂对照，多中心试验。柳叶刀2019年3月22日; [E-PUB]。 （https://doi.org/10.1016/S0140-6736（18）31875-0）