Beta‐blockers in patients with advanced liver disease: Has the dust settled?

Moctezuma‐Velázquez, Carlos; Kalainy, Sylvia; Abraldes, Juan G.

doi:10.1002/lt.24794

Cited by 28 publications

(25 citation statements)

References 61 publications

(152 reference statements)

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“…Our observations support those from other centers describing survival benefit of NSBB use in patients listed for LT [15,19]. The role of NSBB in end stage liver disease and the evidence for potential benefits in decreasing portal pressure, bacterial translocation and systemic inflammation are succinctly summarized in a recent review, and provide a rationale for survival benefit for NSBB use extending beyond the prevention of variceal bleeding [20]. Several factors may also contribute to this finding.…”

Section: Discussionsupporting

confidence: 84%

Non-selective beta blocker use is associated with improved short-term survival in patients with cirrhosis referred for liver transplantation

et al. 2020

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Background: Recent evidence cautions against the use of non-selective beta-blockers (NSBB) in patients with refractory ascites or spontaneous bacterial peritonitis while other data suggests a survival benefit in patients with advanced liver disease. The aim of this study was to describe the use and impact of NSBB in patients with cirrhosis referred for liver transplantation. Methods: A single-center cohort of patients with cirrhosis, who were referred and evaluated for liver transplantation between January and June 2012 were studied for baseline characteristics and clinical outcomes. Patients were grouped according to the use of NSBB at initial evaluation, with the endpoint of 90-day mortality. Results: Sixty-five (38%) of 170 consecutive patients evaluated for liver transplantation were taking NSBB. Patients taking NSBB had higher MELD and Child Pugh score. NSBB use was associated with lower 90-day mortality (6% vs. 15%) with a risk adjusted hazard ratio of 0.27 (95%CI .09-0.88, p = .03). Patients taking NSBB developed acute kidney injury (AKI) within 90 days more frequently than patients not taking NSBB (22% vs 11%), p = 0.048). However, this was related to increased stage 1 AKI episodes, all of which resolved. Twelve (27%) of 45 patients with > 90 day follow up discontinued NSBB, most commonly for hypotension and AKI, had increased subsequent MELD and mortality. Conclusions: NSBB use in patients with cirrhosis undergoing liver transplant evaluation is associated with better short-term survival. Nevertheless, ongoing tolerance of NSBB in this population is dynamic and may select a subset of patients with better hemodynamic reserve.

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Section: Discussionsupporting

confidence: 84%

Non-selective beta blocker use is associated with improved short-term survival in patients with cirrhosis referred for liver transplantation

et al. 2020

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“…Presently, non-selective beta-blockers (NSBB) are the only drug class endorsed for the long-term treatment of portal hypertension[4,5]. Along with endoscopic band ligation, NSBBs are employed for primary and secondary prophylaxis against variceal haemorrhage, as they combat the hyperkinetic portal-hypertensive syndrome by decreasing cardiac output and portal inflow (β-1 receptor blockade) and by achieving splanchnic vasoconstriction and reducing azygos blood flow (β-2 receptor blockade)[1,6-8].…”

Section: Currently-used Medicationsmentioning

confidence: 99%

Current and future pharmacological therapies for managing cirrhosis and its complications

Kockerling

Nathwani

Forlano

et al. 2019

WJG

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Due to the restrictions of liver transplantation, complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis. This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications, together with discussion of current controversies and potential future directions. PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety, efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis. Non-selective beta-blockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices, but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation. Recent observational studies suggest protective, haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation. The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy; recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis. Diuretics remain the mainstay of uncomplicated ascites treatment, and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites. Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications. Despite initial hepatotoxicity concerns, safety of statin administration has been demonstrated in compensated cirrhosis. Furthermore, statins are suggested to have protective effects upon fibrosis progression, decompensation and mortality. Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting. Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis, and may impede hepatic fibrogenesis and decompensation. Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management, nutritional optimisation and patient education.

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“…The authors further recommended that the maximal dose of propranolol should be set at 40–80 mg/day if patients’ MELD score is 18–24 because a high NSBB dose (160 mg/day) is associated with more harmful effects to the systemic circulation and less tolerance. 21 Moctezuma-Velazquez et al 30 have recently summarized practical recommendations proposing that NSBBs should be used cautiously with close monitoring of BP, serum sodium, and creatinine, and should be reduced or discontinued if a patient with refractory ascites develops systolic BP <90 mmHg, hyponatremia <130 mEq/L, or acute kidney injury (AKI).…”

Section: Modification Of Drug Therapymentioning

confidence: 99%

Management of refractory cirrhotic ascites: challenges and solutions

Fukui¹,

Kawaratani²,

Kaji³

et al. 2018

HMER

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Among the various risky complications of liver cirrhosis, refractory ascites is associated with poor survival of cirrhotics and persistently worsens their quality of life (QOL). Major clinical guidelines worldwide define refractory ascites as ascites that cannot be managed by medical therapy either because of a lack of response to maximum doses of diuretics or because patients develop complications related to diuretic therapy that preclude the use of an effective dose of diuretics. Due to the difficulty in receiving a liver transplantation (LT), the ultimate solution for refractory ascites, most cirrhotic patients have selected the palliative therapy such as repeated serial paracentesis, transjugular intrahepatic portosystemic shunt, or peritoneovenous shunt to improve their QOL. During the past several decades, new interventions and methodologies, such as indwelling peritoneal catheter, peritoneal-urinary drainage, and cell-free and concentrated ascites reinfusion therapy, have been introduced. In addition, new medical treatments with vasoconstrictors or vasopressin V2 receptor antagonists have been proposed. Both the benefits and risks of these old and new modalities have been extensively studied in relation to the pathophysiological changes in ascites formation. Although the best solution for refractory ascites is to eliminate hepatic failure either by LT or by causal treatment, the selection of the best palliative therapy for individual patients is of utmost importance, aiming at achieving the longest possible, comfortable life. This review briefly summarizes the changing landscape of variable treatment modalities for cirrhotic patients with refractory ascites, aiming at clarifying their possibilities and limitations. Evolving issues with regard to the impact of gut-derived systemic and local infection on the clinical course of cirrhotic patients have paved the way for the development of a new gut microbiome-based therapeutics. Thus, it should be further investigated whether the early therapeutic approach to gut dysbiosis provides a better solution for the management of cirrhotic ascites.

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Beta‐blockers in patients with advanced liver disease: Has the dust settled?

Cited by 28 publications

References 61 publications

Non-selective beta blocker use is associated with improved short-term survival in patients with cirrhosis referred for liver transplantation

Non-selective beta blocker use is associated with improved short-term survival in patients with cirrhosis referred for liver transplantation

Current and future pharmacological therapies for managing cirrhosis and its complications

Management of refractory cirrhotic ascites: challenges and solutions

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