Accepted Manuscript Car vedilol use is associated with impr oved sur vival in patients with liver cir r hosis and ascites Rohit Sinha, Khalida A. Lockman, Nethmee Mallawaarachchi, Marcus Robertson, John N. Plevris, Peter C. Hayes PII: DOI: Reference:

S0168-8278(17)30073-9 http://dx.doi.org/10.1016/j.jhep.2017.02.005 JHEPAT 6420

To appear in:

Journal of Hepatology

Received Date: Revised Date: Accepted Date:

21 September 2016 20 January 2017 6 February 2017

Please cite this article as: Sinha, R., Lockman, K.A., Mallawaarachchi, N., Robertson, M., Plevris, J.N., Hayes, P.C., Car vedilol use is associated with impr oved sur vival in patients with liver cir r hosis and ascites, Journal of Hepatology (2017), doi: http://dx.doi.org/10.1016/j.jhep.2017.02.005

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Title page Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites.

Rohit Sinha1,2, Khalida A Lockman2, Nethmee Mallawaarachchi2, Marcus Robertson1, John N Plevris1,2, Peter C Hayes1,2

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Liver Unit, 2Hepatology Laboratory,

The Royal Infirmary of Edinburgh and The University of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, UK

Corresponding author: Dr. Rohit Sinha Liver Unit, The Royal Infirmary and The University of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, United Kingdom. Email: [email protected] Telephone: 0044 131 2421625 Fax: 0044 131 2421633

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Keywords: Carvedilol; Non-selective beta-blockers; Ascites; Decompensated liver disease

Electronic word count: 3,392 words

Total Number of Figures: 2

Total Number of Tables: 5

Financial disclosures and conflict of interest: Authors have no financial disclosure or conflict of interest to declare

Authors’ contribution RS collected data, performed statistical analysis and wrote the manuscript. KAL assisted in statistical analysis, data collection, manuscript revision and presentation. NM and MR contributed to data collection. PCH conceptualised the study. All authors reviewed and approved the final manuscript.

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Abstract

Background and aims: Carvedilol, a non-selective beta-blocker (NSBB) with additional antialpha 1 receptor activity, is a potent portal hypotensive agent. It has been used as prophylaxis against variceal bleed. However, its safety in decompensated liver cirrhosis with ascites is still disputed. In this study, we examined whether long-term use of carvedilol in the presence of ascites is a risk factor for mortality.

Methods: This was a single-centre retrospective analysis of 325 consecutive patients with liver cirrhosis and ascites presenting to our Liver Unit between 1st of January 2009 to 31st August 2012. The primary outcome was all-cause and liver-specific mortality in patients receiving or not receiving carvedilol as prophylaxis against variceal bleeding.

Results: The final cohort after propensity score matching comprised 264 patients. Baseline ascites severity and UK End Stage Liver Disease (UKELD) score between carvedilol (n=132) and non-carvedilol (n=132) groups were comparable. Median follow-up time was 2.3 years. Survival at the end of the follow-up was 24% and 2% for carvedilol and non-carvedilol group respectively (Log Rank p

Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites.

Carvedilol, a non-selective beta-blocker (NSBB) with additional anti-alpha 1 receptor activity, is a potent portal hypotensive agent and has been used...
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