Rohit Sinha1, Khalida A Lockman2, Nethmee Mallawaarachchi2, Marcus Robertson3, John N Plevris4, Peter C Hayes4. 1. Liver Unit, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom; Hepatology Laboratory, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom. Electronic address: rohit.sinha@nhs.net. 2. Hepatology Laboratory, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom. 3. Liver Unit, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom. 4. Liver Unit, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom; Hepatology Laboratory, The Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, United Kingdom.
Abstract
BACKGROUND & AIMS: Carvedilol, a non-selective beta-blocker (NSBB) with additional anti-alpha 1 receptor activity, is a potent portal hypotensive agent and has been used as prophylaxis against variceal bleeding. However, its safety in patients with decompensated liver cirrhosis and ascites is still disputed. In this study, we examined whether long-term use of carvedilol in patients with ascites is a risk factor for mortality. METHODS: 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 was carried out. 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) treated patient groups were comparable. Median follow-up time was 2.3years. Survival at the end of the follow-up was 24% and 2% for the carvedilol and the non-carvedilol groups respectively (log-rank p<0.0001). The long-term survival was significantly better in carvedilol than non-carvedilol group (log-rank p<0.001). The survival difference remained significant after adjusting for age, gender, ascites severity, aetiology of cirrhosis, previous variceal bleed, spontaneous bacterial peritonitis prophylaxis, serum albumin and UKELD with hazard ratio of 0.59 (95% confidence interval [CI]: 0.44, 0.80; p=0.001), suggesting a 41% reduction in mortality risk. When stratified by the severity of ascites, carvedilol therapy resulted in hazard ratio of 0.47 (95% CI: 0.29, 0.77; p=0.003) in those with mild ascites. Even with moderate or severe ascites, carvedilol use was not associated with increased mortality risk. CONCLUSION: Long-term carvedilol therapy is not harmful in patients with decompensated cirrhosis and ascites. LAY SUMMARY: The safety of carvedilol and other non-selective beta-blocker drugs in patients with liver cirrhosis and ascites is still debated. In this study, we have shown that carvedilol therapy in these patients was associated with reduced risk of mortality, particularly in those with mild ascites. We concluded that low dose, chronic treatment with carvedilol in patients with liver cirrhosis and ascites is not detrimental.
BACKGROUND & AIMS:Carvedilol, a non-selective beta-blocker (NSBB) with additional anti-alpha 1 receptor activity, is a potent portal hypotensive agent and has been used as prophylaxis against variceal bleeding. However, its safety in patients with decompensated liver cirrhosis and ascites is still disputed. In this study, we examined whether long-term use of carvedilol in patients with ascites is a risk factor for mortality. METHODS: 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 was carried out. 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) treated patient groups were comparable. Median follow-up time was 2.3years. Survival at the end of the follow-up was 24% and 2% for the carvedilol and the non-carvedilol groups respectively (log-rank p<0.0001). The long-term survival was significantly better in carvedilol than non-carvedilol group (log-rank p<0.001). The survival difference remained significant after adjusting for age, gender, ascites severity, aetiology of cirrhosis, previous variceal bleed, spontaneous bacterial peritonitis prophylaxis, serum albumin and UKELD with hazard ratio of 0.59 (95% confidence interval [CI]: 0.44, 0.80; p=0.001), suggesting a 41% reduction in mortality risk. When stratified by the severity of ascites, carvedilol therapy resulted in hazard ratio of 0.47 (95% CI: 0.29, 0.77; p=0.003) in those with mild ascites. Even with moderate or severe ascites, carvedilol use was not associated with increased mortality risk. CONCLUSION: Long-term carvedilol therapy is not harmful in patients with decompensated cirrhosis and ascites. LAY SUMMARY: The safety of carvedilol and other non-selective beta-blocker drugs in patients with liver cirrhosis and ascites is still debated. In this study, we have shown that carvedilol therapy in these patients was associated with reduced risk of mortality, particularly in those with mild ascites. We concluded that low dose, chronic treatment with carvedilol in patients with liver cirrhosis and ascites is not detrimental.
Authors: Nikolaus Pfisterer; Caroline Schmidbauer; Florian Riedl; Andreas Maieron; Vanessa Stadlbauer; Barbara Hennlich; Remy Schwarzer; Andreas Puespoek; Theresa Bucsics; Maria Effenberger; Simona Bota; Michael Gschwantler; Markus Peck-Radosavljevic; Mattias Mandorfer; Christian Madl; Michael Trauner; Thomas Reiberger Journal: Wien Klin Wochenschr Date: 2020-12-03 Impact factor: 1.704
Authors: Dhiraj Tripathi; Peter Clive Hayes; Paul Richardson; Ian Rowe; James Ferguson; Peter Devine; Jonathan Mathers; Christopher Poyner; Sue Jowett; Kelly Handley; Margaret Grant; Gemma Slinn; Khaled Ahmed; Peter Brocklehurst Journal: BMJ Open Gastroenterol Date: 2019-04-25
Authors: David Kockerling; Rooshi Nathwani; Roberta Forlano; Pinelopi Manousou; Benjamin H Mullish; Ameet Dhar Journal: World J Gastroenterol Date: 2019-02-28 Impact factor: 5.742