Non-selective beta-blockers may reduce risk of hepatocellular carcinoma: a meta-analysis of randomized trials

Maja Thiele; Agustín Albillos; Rozeta Abazi; Reiner Wiest; Lise L Gluud; Aleksander Krag

doi:10.1111/liv.12782

Non-selective beta-blockers may reduce risk of hepatocellular carcinoma: a meta-analysis of randomized trials

Maja Thiele, Agustín Albillos, Rozeta Abazi, Reiner Wiest, Lise L Gluud, Aleksander Krag

Department of Clinical Medicine

33 Citations (Scopus)

Abstract

BACKGROUND & AIMS: 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 Authors were contacted for unpublished data.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.

Original language	English
Journal	Liver International
Volume	35
Issue number	8
Pages (from-to)	2009-16
Number of pages	8
ISSN	1478-3223
DOIs	https://doi.org/10.1111/liv.12782
Publication status	Published - 1 Aug 2015

Keywords

Adrenergic beta-Antagonists
Aged
Carcinoma, Hepatocellular
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Humans
Liver Cirrhosis
Liver Neoplasms
Male
Middle Aged
Neovascularization, Pathologic
Randomized Controlled Trials as Topic
Risk Assessment
Survival Analysis
Treatment Outcome

Access to Document

10.1111/liv.12782Licence: CC BY

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/liv.12782Licence: CC BY

Cite this

@article{8c7c636b88dd4fc6b080faa915fb47c6,

title = "Non-selective beta-blockers may reduce risk of hepatocellular carcinoma: a meta-analysis of randomized trials",

abstract = "BACKGROUND & AIMS: 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.",

keywords = "Adrenergic beta-Antagonists, Aged, Carcinoma, Hepatocellular, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Liver Cirrhosis, Liver Neoplasms, Male, Middle Aged, Neovascularization, Pathologic, Randomized Controlled Trials as Topic, Risk Assessment, Survival Analysis, Treatment Outcome",

author = "Maja Thiele and Agust{\'i}n Albillos and Rozeta Abazi and Reiner Wiest and Gluud, {Lise L} and Aleksander Krag",

note = "{\textcopyright} 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",

year = "2015",

month = aug,

day = "1",

doi = "10.1111/liv.12782",

language = "English",

volume = "35",

pages = "2009--16",

journal = "Liver International",

issn = "1478-3223",

publisher = "Wiley-Blackwell",

number = "8",

}

TY - JOUR

T1 - Non-selective beta-blockers may reduce risk of hepatocellular carcinoma

T2 - a meta-analysis of randomized trials

AU - Thiele, Maja

AU - Albillos, Agustín

AU - Abazi, Rozeta

AU - Wiest, Reiner

AU - Gluud, Lise L

AU - Krag, Aleksander

PY - 2015/8/1

Y1 - 2015/8/1

N2 - BACKGROUND & AIMS: 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.

AB - BACKGROUND & AIMS: 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.

KW - Adrenergic beta-Antagonists

KW - Aged

KW - Carcinoma, Hepatocellular

KW - Dose-Response Relationship, Drug

KW - Drug Administration Schedule

KW - Female

KW - Humans

KW - Liver Cirrhosis

KW - Liver Neoplasms

KW - Male

KW - Middle Aged

KW - Neovascularization, Pathologic

KW - Randomized Controlled Trials as Topic

KW - Risk Assessment

KW - Survival Analysis

KW - Treatment Outcome

U2 - 10.1111/liv.12782

DO - 10.1111/liv.12782

M3 - Journal article

C2 - 25581713

SN - 1478-3223

VL - 35

SP - 2009

EP - 2016

JO - Liver International

JF - Liver International

IS - 8

ER -

Non-selective beta-blockers may reduce risk of hepatocellular carcinoma: a meta-analysis of randomized trials

Abstract

Keywords

Access to Document

Fingerprint

Cite this