Systemic arterial blood pressure determines the therapeutic window of non-selective beta blockers in decompensated cirrhosis.
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
16
04
2019
revised:
10
05
2019
accepted:
05
07
2019
pubmed:
3
8
2019
medline:
21
5
2020
entrez:
3
8
2019
Statut:
ppublish
Résumé
The safety of non-selective β-blockers in patients with advanced cirrhosis has been questioned in recent years. It was hypothesised that there is a particular therapeutic window. However, the specific limits still need to be determined. To evaluate potential limits of the therapeutic window of non-selective β-blocker therapy in patients with cirrhosis and ascites METHODS: The impact of non-selective β-blockers on 28-day transplant-free survival was analysed in a cohort of 624 consecutive patients with decompensated cirrhosis and ascites. Three potential limits were investigated: spontaneous bacterial peritonitis, acute-on-chronic liver failure, mean arterial blood pressure ≤ 82 and < 65 mm Hg. Treatment with non-selective β-blockers was associated with a higher 28-day transplant-free survival in the overall cohort (hazard ratio: 0.621; P = .035) as well as in patients with acute-on-chronic liver failure (hazard ratio: 0.578; P = .031) and those with spontaneous bacterial peritonitis (hazard ratio: 0.594; P = .073). In contrast, survival benefits were markedly attenuated in patients with a mean arterial blood pressure ≤ 82 mm Hg and completely lost in those with mean arterial blood pressure < 65 mm Hg (P = .536). In spontaneous bacterial peritonitis patients with a mean arterial blood pressure < 65 mm Hg non-selective β-blocker treatment was associated with renal impairment. Of note, among those with a mean arterial blood pressure ≥ 65 mm Hg non-selective β-blocker intake was consistently associated with superior transplant-free survival (hazard ratio: 0.582; P = .029) irrespective of the presence of spontaneous bacterial peritonitis (hazard ratio: 0.435; P = .028) or acute-on-chronic liver failure (hazard ratio: 0.480 P = .034). Ascites, acute-on-chronic liver failure and spontaneous bacterial peritonitis do not limit the safe use of non-selective β-blockers in patients with cirrhosis. Mean arterial blood pressure might represent a better indicator to determine the therapeutic window of non-selective β-blocker treatment.
Sections du résumé
BACKGROUND
The safety of non-selective β-blockers in patients with advanced cirrhosis has been questioned in recent years. It was hypothesised that there is a particular therapeutic window. However, the specific limits still need to be determined.
AIM
To evaluate potential limits of the therapeutic window of non-selective β-blocker therapy in patients with cirrhosis and ascites METHODS: The impact of non-selective β-blockers on 28-day transplant-free survival was analysed in a cohort of 624 consecutive patients with decompensated cirrhosis and ascites. Three potential limits were investigated: spontaneous bacterial peritonitis, acute-on-chronic liver failure, mean arterial blood pressure ≤ 82 and < 65 mm Hg.
RESULTS
Treatment with non-selective β-blockers was associated with a higher 28-day transplant-free survival in the overall cohort (hazard ratio: 0.621; P = .035) as well as in patients with acute-on-chronic liver failure (hazard ratio: 0.578; P = .031) and those with spontaneous bacterial peritonitis (hazard ratio: 0.594; P = .073). In contrast, survival benefits were markedly attenuated in patients with a mean arterial blood pressure ≤ 82 mm Hg and completely lost in those with mean arterial blood pressure < 65 mm Hg (P = .536). In spontaneous bacterial peritonitis patients with a mean arterial blood pressure < 65 mm Hg non-selective β-blocker treatment was associated with renal impairment. Of note, among those with a mean arterial blood pressure ≥ 65 mm Hg non-selective β-blocker intake was consistently associated with superior transplant-free survival (hazard ratio: 0.582; P = .029) irrespective of the presence of spontaneous bacterial peritonitis (hazard ratio: 0.435; P = .028) or acute-on-chronic liver failure (hazard ratio: 0.480 P = .034).
CONCLUSIONS
Ascites, acute-on-chronic liver failure and spontaneous bacterial peritonitis do not limit the safe use of non-selective β-blockers in patients with cirrhosis. Mean arterial blood pressure might represent a better indicator to determine the therapeutic window of non-selective β-blocker treatment.
Substances chimiques
Adrenergic beta-Antagonists
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
696-706Subventions
Organisme : Else Kröner-Fresenius-Stiftung
Pays : International
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2019 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd.
Références
Reiberger T, Mandorfer M. Beta adrenergic blockade and decompensated cirrhosis. J Hepatol. 2017;66:849-859.
Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology. 2017;65:310-335.
Lebrec D, Poynard T, Hillon P, Benhamou JP. Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a controlled study. N Engl J Med. 1981;305:1371-1374.
de Franchis R, Baveno VI Faculty. Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63:743-752.
Gotz M, Anders M, Biecker E, et al. S2k Guideline Gastrointestinal Bleeding - Guideline of the German Society of Gastroenterology DGVS. Z Gastroenterol. 2017;55:883-936.
Sersté T, Francoz C, Durand F, et al. Beta-blockers cause paracentesis-induced circulatory dysfunction in patients with cirrhosis and refractory ascites: a cross-over study. J Hepatol. 2011;55:794-799.
Sersté T, Melot C, Francoz C, et al. Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites. Hepatology. 2010;52:1017-1022.
Krag A, Wiest R, Albillos A, Gluud LL. The window hypothesis: haemodynamic and non-haemodynamic effects of beta-blockers improve survival of patients with cirrhosis during a window in the disease. Gut. 2012;61:967-969.
Bossen L, Krag A, Vilstrup H, Watson H, Jepsen P. Nonselective beta-blockers do not affect mortality in cirrhosis patients with ascites: post hoc analysis of three randomized controlled trials with 1198 patients. Hepatology. 2016;63:1968-1976.
Leithead JA, Rajoriya N, Tehami N, et al. Non-selective beta-blockers are associated with improved survival in patients with ascites listed for liver transplantation. Gut. 2015;64:1111-1119.
Onali S, Kalafateli M, Majumdar A, et al. Non-selective beta-blockers are not associated with increased mortality in cirrhotic patients with ascites. Liver Int. 2017;37:1334-1344.
Mandorfer M, Bota S, Schwabl P, et al. Nonselective beta blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterology. 2014;146:1680-1690.e1.
Wiest R, Krag A, Gerbes A. Spontaneous bacterial peritonitis: recent guidelines and beyond. Gut. 2012;61:297-310.
Moreau R, Jalan R, Gines P, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144:1426-1437.e9.
Ge PS, Runyon BA. When should the beta-blocker window in cirrhosis close? Gastroenterology. 2014;146:1597-1599.
European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406-460.
Mookerjee RP, Pavesi M, Thomsen KL, et al. Treatment with non-selective beta blockers is associated with reduced severity of systemic inflammation and improved survival of patients with acute-on-chronic liver failure. J Hepatol. 2016;64:574-582.
Garcia-Tsao G. Beta blockers in cirrhosis: the window re-opens. J Hepatol. 2016;64:532-534.
Madsen BS, Nielsen KF, Fialla AD, Krag A. Keep the sick from harm in spontaneous bacterial peritonitis: dose of beta blockers matters. J Hepatol. 2016;64:1455-1456.
Tergast TL, Laser H, Gerbel S, Manns MP, Cornberg M, Maasoumy B. Association between type 2 diabetes mellitus, HbA1c and the risk for spontaneous bacterial peritonitis in patients with decompensated liver cirrhosis and ascites. Clin Transl Gastroenterol. 2018;9:e189.
Tergast TL, Wranke A, Laser H, et al. Dose dependent impact of proton pump inhibitors on the clinical course of spontaneous bacterial peritonitis. Liver Int. 2018;38:1602-1613.
Gerbes AL, Gulberg V, Sauerbruch T, et al. German S 3-guideline "ascites, spontaneous bacterial peritonitis, hepatorenal syndrome". Z Gastroenterol. 2011;49:749-779.
Angeli P, Gines P, Wong F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. Gut. 2015;64:531-537.
Llach J, Ginès P, Arroyo V, et al. Prognostic value of arterial pressure, endogenous vasoactive systems, and renal function in cirrhotic patients admitted to the hospital for the treatment of ascites. Gastroenterology. 1988;94:482-487.
Varpula M, Tallgren M, Saukkonen K, Voipio-Pulkki LM, Pettila V. Hemodynamic variables related to outcome in septic shock. Intensive Care Med. 2005;31:1066-1071.
Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33:464-470.
Berzigotti A, Seijo S, Arena U, et al. Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis. Gastroenterology. 2013;144:102-111.e1.
Kuk D, Varadhan R. Model selection in competing risks regression. Stat Med. 2013;32:3077-3088.
Krag A, Bendtsen F, Henriksen JH, Moller S. Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites. Gut. 2010;59:105-110.
Mandorfer M, Reiberger T. Role of diuretics in the harmful effects of beta blockers in patients with ascites. Author's reply. Dig Liver Dis. 2018;50:102-103.
Sersté T, Njimi H, Degré D, et al. The use of beta-blockers is associated with the occurrence of acute kidney injury in severe alcoholic hepatitis. Liver international. 2015;35:1974-1982.
Bang UC, Benfield T, Hyldstrup L, Jensen JE, Bendtsen F. Effect of propranolol on survival in patients with decompensated cirrhosis: a nationwide study based Danish patient registers. Liver Int. 2016;36:1304-1312.
Robins A, Bowden A, Watson W, Smith F, Gelson W, Griffiths W. Beta-blockers in cirrhosis patients with refractory ascites. Hepatology. 2014;59:2054-2055.
Worlicek M, Knebel K, Linde HJ, et al. Splanchnic sympathectomy prevents translocation and spreading of E coli but not S aureus in liver cirrhosis. Gut. 2010;59:1127-1134.
Reiberger T, Ferlitsch A, Payer BA, et al. Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis. J Hepatol. 2013;58:911-921.
Pérez-Paramo M, Muñoz J, Albillos A, et al. Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites. Hepatology. 2000;31:43-48.
Bhutta AQ, Garcia-Tsao G, Reddy KR, et al. Beta-blockers in hospitalised patients with cirrhosis and ascites: mortality and factors determining discontinuation and reinitiation. Aliment Pharmacol Ther. 2018;47:78-85.
Payancé A, Bissonnette J, Roux O, et al. Lack of clinical or haemodynamic rebound after abrupt interruption of beta-blockers in patients with cirrhosis. Aliment Pharmacol Ther. 2016;43:966-973.