title: 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.
abstract: OBJECTIVE
  Non-selective beta blockers (NSBBs) have been shown to have deleterious outcomes in patients with refractory ascites, alcoholic hepatitis and spontaneous bacterial peritonitis leading many physicians to stop the drug in these cases. Acute-on-chronic liver failure (ACLF) is characterized by systemic inflammation and high mortality. As NSBBs may have beneficial effects on gut motility and permeability and, systemic inflammation, the aims of this prospective, observational study were to determine whether ongoing use of NSBBs reduced 28-day mortality in ACLF patients.
  
  
  METHODS
  The study was performed in 349 patients with ACLF included in the CANONIC study, which is a prospective observational investigation in hospitalized cirrhotic patients with acute deterioration. The data about the use of NSBBs, its type and dosage was specifically recorded. Patient characteristics at enrollment significantly associated with treatment and mortality were taken into account as potential confounders to adjust for treatment effect. A logistic regression model was fitted.
  
  
  RESULTS
  164 (47%) ACLF patients received NSBBs whereas 185 patients did not. Although the CLIF-C ACLF scores were similar at presentation, more patients in the NSBB treated group had lower grades of ACLF (p=0.047) at presentation and significantly more patients improved. Forty patients (24.4%) died in NSBB treated group compared with 63 patients (34.1%) (p=0.048) [estimated risk-reduction 0.596 (95%CI: 0.361-0.985; p=0.0436)]. This improvement in survival was associated with a significantly lower white cell count (NSBB: 8.5 (5.8); no NSBB: 10.8 (6.6); p=0.002). No long-term improvement in survival was observed.
  
  
  CONCLUSIONS
  This study shows for the first time that ongoing treatment with NSBBs in cirrhosis is safe and reduces the mortality if they develop ACLF. Careful thought should be given before stopping NSBBs in cirrhotic patients.
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, United Kingdom.
authors.forename: Rajeshwar P
authors.initials: RP
authors.lastname: Mookerjee
authors.affiliation: European Foundation for the Study of Chronic Liver Failure (EF-CLIF) and EASL-CLIF Consortium.
authors.forename: Marco
authors.initials: M
authors.lastname: Pavesi
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, United Kingdom.
authors.forename: Karen Louise
authors.initials: KL
authors.lastname: Thomsen
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, United Kingdom.
authors.forename: Gautam
authors.initials: G
authors.lastname: Mehta
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Macnaughtan
authors.affiliation: Department of Gastroenterology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Bendtsen
authors.affiliation: Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Minneke
authors.initials: M
authors.lastname: Coenraad
authors.affiliation: Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Sperl
authors.affiliation: Liver Unit, Hospital Clínic de Barcelona, University de Barcelona, Barcelona, Spain; University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain; Centro d'Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEReHD), Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Gines
authors.affiliation: Inserm, U1149, Centre de Recherche sur l'Inflammation (CRI), Clichy and Paris, France; UMRS1149, Université Paris Diderot-Paris 7, Paris, France; Département Hospitalo-Universitaire (DHU) UNITY, Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France; Laboratoire d'Excellence Inflamex, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Moreau
authors.affiliation: European Foundation for the Study of Chronic Liver Failure (EF-CLIF) and EASL-CLIF Consortium.
authors.forename: Vicente
authors.initials: V
authors.lastname: Arroyo
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, United Kingdom. Electronic address: r.jalan@ucl.ac.uk.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000401:mortality; D007958:Leukocyte Count; D008103:Liver Cirrhosis / Q000150:complications; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000319:Adrenergic beta-Antagonists
keywords: Acute-on-chronic liver failure; Cirrhosis; Multi-organ failure; Non-selective beta blockers; Prognosis; Sepsis