β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial

Villanueva, Càndid; Albillos, Agustı́n; Genescà, Joan; García–Pagán, Joan Carles; Calleja, José Luís; Aracil, Carles; Bañares, Rafael; Morillas, Rosa; Poca, María; Peñas, Beatriz; Augustín, Salvador; Abraldes, Juan G.; Alvarado, Edilmar; Torres, Ferrán; Bosch, Jaume

doi:10.1016/s0140-6736(18)31875-0

Cited by 404 publications

(378 citation statements)

References 29 publications

Supporting

Mentioning

352

Contrasting

Unclassified

Order By: Relevance

“…The interrelation between degree of portal hypertension and CO has been pivotal in the classical vasodilation hypothesis of portal hypertension in cirrhosis 5‐8 . Moreover, this pathophysiological view represents the rational basis for the use of NSBB in the treatment and prevention of portal hypertensive complications 22‐24 . Nevertheless, considering that CI >4.2 L/min/m 2 is found almost only in patients with CSPH, it is tempting to hypothesize that inflammation may be a main pathogenetic driver of disease progression in hyperdynamic cirrhotic patients 25‐29 .…”

Section: Discussionmentioning

confidence: 99%

Cardiodynamic state is associated with systemic inflammation and fatal acute‐on‐chronic liver failure

Praktiknjo

Monteiro

Grandt

et al. 2020

Liver International

View full text Add to dashboard Cite

Background & Aims:Acute-on-chronic liver failure (ACLF) is characterized by high short-term mortality and systemic inflammation (SI). Recently, different cardiodynamic states were shown to independently predict outcomes in cirrhosis. The relationship between cardiodynamic states, SI, and portal hypertension and their impact on ACLF development remains unclear. The aim of this study was therefore to evaluate the interplay of cardiodynamic state and SI on fatal ACLF development in cirrhosis. Results: At inclusion, hemodynamic measures including cardiac index (CI) and hepaticvenous pressure gradient of 208 patients were measured. Patients were followed prospectively for fatal ACLF development (primary endpoint). SI was assessed by proinflammatory markers such as interleukins (ILs) 6 and 8 and soluble IL-33 receptor (sIL-33R). Patients were divided according to CI (<3.2; 3.2-4.2; >4.2 L/min/m 2 ) in hypo-(n = 84), normo-(n = 69) and hyperdynamic group (n = 55). After a median follow-up of 3 years, the highest risk of fatal ACLF was seen in hyperdynamic (35%) and hypodynamic patients (25%) compared with normodynamic (14%) (P = .011).Hyperdynamic patients showed the highest rate of SI. The detectable level of IL-6 was an independent predictor of fatal ACLF development. Conclusions: Cirrhotic patients with hyperdynamic and hypodynamic circulationhave a higher risk of fatal ACLF. Therefore, the cardiodynamic state is strongly associated with SI, which is an independent predictor of development of fatal ACLF.Correspondence acute-on-chronic liver failure, circulation, cirrhosis, hemodynamic, inflammation Key points• Acute-on-chronic liver failure (ACLF) is suggested to be associated with systemic inflammation (SI).• The impact of systemic circulation (cardiodynamic state) and SI on ACLF development is not fully elucidated.• This study shows that cirrhotic patients with hyperdynamic and hypodynamic circulatory state have a higher risk of fatal ACLF.• Hyperdynamic state is strongly associated with SI, which independently predicts fatal ACLF development.

show abstract

Section: Discussionmentioning

confidence: 99%

Cardiodynamic state is associated with systemic inflammation and fatal acute‐on‐chronic liver failure

Praktiknjo

Monteiro

Grandt

et al. 2020

Liver International

View full text Add to dashboard Cite

show abstract

“…We call for more studies that exclusively evaluate patients with compensated advanced chronic liver disease. The identification of cirrhosis patients with CSPH before decompensation is important according to a recent RCT, as those patients could benefit from primary prevention with non‐selective beta‐blockers 27 . For this reason, it is unfortunate that existing studies primarily represent decompensated patients.…”

Section: Discussionmentioning

confidence: 99%

2D shear wave liver elastography by Aixplorer to detect portal hypertension in cirrhosis: An individual patient data meta‐analysis

Thiele

Hugger

Kim

et al. 2020

Liver International

View full text Add to dashboard Cite

Background & Aims: Liver stiffness measured with 2-dimensional shear wave elastography by Supersonic Imagine (2DSWE-SSI) is well-established for fibrosis diagnostics, but non-conclusive for portal hypertension. Methods:We performed an individual patient data meta-analysis of 2DSWE-SSI to identify clinically significant portal hypertension (CSPH), severe portal hypertension and large varices in cirrhosis patients, using hepatic venous pressure gradient

show abstract

“…In fact, in the study comparing tImolol or placebo for the prevention of varices, the development of varices led to drug discontinuation, precluding assessment of a potential effect on the development of ascites or other decompensating events. Very recent data, suggest that NSBBs might have a strong effect preventing ascites in patients with cirrhosis and CSPH …”

Section: Phase 3 Trials In Phmentioning

confidence: 99%

“…Very recent data, suggest that NSBBs might have a strong effect preventing ascites in patients with cirrhosis and CSPH. (43) The development of varices should be assessed as a secondary endpoint, but should not be part of the primary endpoint and should not lead to study drug discontinuation. This secondary endpoint could be analyzed as an exploratory ordinal outcome (considering death as the worst potential outcome, followed by decompensation and varices; Fig.…”

Section: Development Of Varices As a Part Of The Main Primary Endpointmentioning

confidence: 99%

Prioritization of Therapeutic Targets and Trial Design in Cirrhotic Portal Hypertension

et al. 2019

View full text Add to dashboard Cite

Portal hypertension (PH) is the main driver of cirrhosis decompensation, the main determinant of death in patients with cirrhosis. PH results initially from increased intrahepatic vascular resistance. Subsequently, increased inflow from splanchnic vasodilation and increased cardiac output lead to a further increase in portal pressure (PP). Reducing PP in cirrhosis results in better outcomes. Removing the cause of cirrhosis might improve PP. However, this is a slow process and patients may continue to be at risk of decompensation. Additionally, for some chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD), etiological treatments are not yet available. Therefore, there is a need to develop better therapies specifically aimed at reducing PP. For over 35 years, the mainstay of such therapy has been the use of nonselective beta‐blockers (NSBBs) that act by reducing portal venous inflow. Recently, many drugs (mainly targeting intrahepatic mechanisms) have shown promise in preclinical and early clinical studies and may act alone or synergistically with NSBBs in reducing PP in cirrhosis. The objective of this position paper is to propose a novel framework for the design of clinical trials (phase 1, 2, and 3) in patients with cirrhosis and PH and to prioritize targets and pharmacological therapies in this setting. We have focused the discussion on patients with compensated cirrhosis. The paper summarizes discussions held at The American Association for the Study of Liver Diseases (AASLD) Industry Colloquium in January 2018, with the participation of clinical and translational investigators, regulatory professionals, and industry partners.

show abstract

β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial

Cited by 404 publications

References 29 publications

Cardiodynamic state is associated with systemic inflammation and fatal acute‐on‐chronic liver failure

Cardiodynamic state is associated with systemic inflammation and fatal acute‐on‐chronic liver failure

2D shear wave liver elastography by Aixplorer to detect portal hypertension in cirrhosis: An individual patient data meta‐analysis

Prioritization of Therapeutic Targets and Trial Design in Cirrhotic Portal Hypertension

Contact Info

Product

Resources

About