title: Non-selective beta-blockers may reduce risk of hepatocellular carcinoma: a meta-analysis of randomized trials.
abstract: OBJECTIVE
  Non-selective beta-blockers (NSBB) are used in patients with cirrhosis and oesophageal varices. Experimental data suggest that NSBB inhibit angiogenesis and reduce bacterial translocation, which may prevent hepatocellular carcinoma (HCC). We therefore assessed the effect of NSBB on HCC by performing a systematic review with meta-analyses of randomized trials.
  
  
  METHODS
  Electronic and manual searches were combined. Authors were contacted for unpublished data. Included trials assessed NSBB for patients with cirrhosis; the control group could receive any other intervention than NSBB. Fixed and random effects meta-analyses were performed with I(2) as a measure of heterogeneity. Subgroup, sensitivity, regression and sequential analyses were performed to evaluate heterogeneity, bias and the robustness of the results after adjusting for multiple testing.
  
  
  RESULTS
  Twenty-three randomized trials on 2618 patients with cirrhosis were included, of which 12 reported HCC incidence and 23 reported HCC mortality. The mean duration of follow-up was 26 months (range 8-82). In total, 47 of 694 patients randomized to NSBB developed HCC vs 65 of 697 controls (risk difference -0.026; 95% CI-0.052 to -0.001; number needed to treat 38 patients). There was no heterogeneity (I(2) = 7%) or evidence of small study effects (Eggers P = 0.402). The result was not confirmed in sequential analysis, which suggested that 3719 patients were needed to achieve the required information size. NSBB did not reduce HCC-related mortality (RD -0.011; 95% CI -0.040 to 0.017).
  
  
  CONCLUSIONS
  Non-selective beta-blockers may prevent HCC in patients with cirrhosis.
authors.affiliation: Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.
authors.forename: Maja
authors.initials: M
authors.lastname: Thiele
authors.affiliation: Department of Gastroenterology and Hepatology, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Institute of Health Carlos III, University Hospital Ramón y Cajal, University of Alcalá, IRYCIS, Madrid, Spain.
authors.forename: Agustín
authors.initials: A
authors.lastname: Albillos
authors.affiliation: Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.
authors.forename: Rozeta
authors.initials: R
authors.lastname: Abazi
authors.affiliation: Department for Visceral Surgery and Medicine, University Hospital Bern, Bern, Switzerland.
authors.forename: Reiner
authors.initials: R
authors.lastname: Wiest
authors.affiliation: Gastro unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Lise L
authors.initials: LL
authors.lastname: Gluud
authors.affiliation: Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Krag
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists
keywords: beta-adrenergic antagonists; hepatocellular carcinoma; liver cancer