Review article: controversies surrounding the use of carvedilol and other beta blockers in the management of portal hypertension and cirrhosis

被引:12
作者
Gillespie, Sarah-Louise [1 ]
Hanrahan, Timothy P. P. [1 ,2 ]
Rockey, Don C. C. [3 ]
Majumdar, Avik [2 ,4 ]
Hayes, Peter C. C. [1 ,5 ]
机构
[1] Royal Infirm Edinburgh NHS Trust, Ctr Liver & Digest Disorders, Edinburgh, Scotland
[2] Dept Gastroenterol & Hepatol, Austin Hlth, Melbourne, Australia
[3] Med Univ South Carolina, Digest Dis Res Ctr, Charleston, SC USA
[4] Univ Melbourne, Melbourne, Australia
[5] Univ Edinburgh, Coll Med & Vet Med, Edinburgh, Scotland
关键词
cirrhosis; Clinical Pharmacology; portal hypertension; varices; VARICEAL BAND LIGATION; SMALL ESOPHAGEAL-VARICES; PRIMARY PROPHYLAXIS; OXIDATIVE STRESS; HEMODYNAMIC-RESPONSE; IMPROVED SURVIVAL; PHARMACOLOGICAL-TREATMENT; ENDOTHELIAL DYSFUNCTION; COMPENSATED CIRRHOSIS; NRF2-ARE PATHWAY;
D O I
10.1111/apt.17380
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
BackgroundAdvanced chronic liver disease is an increasing cause of premature morbidity and mortality in the UK. Portal hypertension is the primary driver of decompensation, including the development of ascites, hepatic encephalopathy and variceal haemorrhage. Non-selective beta blockers (NSBB) reduce portal pressure and are well established in the prevention of variceal haemorrhage. Carvedilol, a newer NSBB, is more effective at reducing portal pressure due to additional alpha-adrenergic blockade and has additional anti-oxidant, anti-inflammatory and anti-fibrotic effects. AimTo summarise the available evidence on the use of beta blockers, specifically carvedilol, in cirrhosis, focussing on when and why to start MethodsWe performed a comprehensive literature search of PubMed for relevant publications. ResultsInternational guidelines advise the use of NSBB in primary prophylaxis against variceal haemorrhage in those with high-risk varices, with substantial evidence of efficacy comparable with endoscopic band ligation (EBL). NSBB are also well established in secondary prophylaxis, in combination with EBL. More controversial is their use in patients without large varices, but with clinically significant portal hypertension. However, there is gathering evidence that NSBB, particularly carvedilol, reduce the risk of decompensation and improve survival. While caution is advised in patients with advanced cirrhosis and refractory ascites, recent evidence suggests that NSBB can continue to be used safely, and that premature discontinuation may be detrimental. ConclusionsWith increasing evidence of benefit independent of variceal bleeding, namely retardation of decompensation and improvement in survival, it is time to consider whether carvedilol should be offered to all patients with advanced chronic liver disease.
引用
收藏
页码:454 / 463
页数:10
相关论文
共 101 条
[21]   Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells [J].
de Araujo Junior, Raimundo Fernandes ;
Garcia, Vinicius Barreto ;
de Carvalho Leitao, Renata Ferreira ;
de Castro Brito, Gerly Anne ;
Miguel, Emilio de Castro ;
Matta Guedes, Paulo Marcos ;
de Araujo, Aurigena Antunes .
PLOS ONE, 2016, 11 (02)
[22]   Baveno VII - Renewing consensus in portal hypertension [J].
de Franchis, Roberto ;
Bosch, Jaime ;
Garcia-Tsao, Guadalupe ;
Reiberger, Thomas ;
Ripoll, Cristina .
JOURNAL OF HEPATOLOGY, 2022, 76 (04) :959-974
[23]   Carvedilol may attenuate liver cirrhosis by inhibiting angiogenesis through the VEGF-Src-ERK signaling pathway [J].
Ding, Qian ;
Tian, Xiang-Guo ;
Li, Yan ;
Wang, Qi-Zhi ;
Zhang, Chun-Qing .
WORLD JOURNAL OF GASTROENTEROLOGY, 2015, 21 (32) :9566-9576
[24]   Carvedilol versus endoscopic band ligation for secondary prophylaxis of variceal bleeding-Long-term follow-up of a randomised control trial [J].
Dunne, Philip D. J. ;
Young, David ;
Chuah, Cher Shiong ;
Hayes, Peter C. ;
Tripathi, Dhiraj ;
Leithead, Joanna ;
Smith, Lyn A. ;
Gaya, Daniel R. ;
Forrest, Ewan ;
Stanley, Adrian J. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2022, 55 (12) :1581-1587
[25]   Predictive value of the variceal pressure response to continued pharmacological therapy in patients with cirrhosis and portal hypertension [J].
Escorsell, A ;
Bordas, JM ;
Castañeda, B ;
Llach, J ;
García-Pagán, JC ;
Rodés, J ;
Bosch, J .
HEPATOLOGY, 2000, 31 (05) :1061-1067
[26]   EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis [J].
Angeli P. ;
Bernardi M. ;
Villanueva C. ;
Francoz C. ;
Mookerjee R.P. ;
Trebicka J. ;
Krag A. ;
Laleman W. ;
Gines P. .
JOURNAL OF HEPATOLOGY, 2018, 69 (02) :406-460
[27]   Acute haemodynamic changes after oral carvedilol, a vasodilating beta-blocker, in patients with cirrhosis [J].
Forrest, EH ;
Bouchier, IAD ;
Hayes, PC .
JOURNAL OF HEPATOLOGY, 1996, 25 (06) :909-915
[28]   Meta-analysis: beta-blockers versus banding ligation for primary prophylaxis of esophageal variceal bleeding [J].
Funakoshi, Natalie ;
Duny, Yohan ;
Valats, Jean-Christophe ;
Segalas-Largey, Frederique ;
Flori, Nicolas ;
Bismuth, Michael ;
Daures, Jean-Pierre ;
Blanc, Pierre .
ANNALS OF HEPATOLOGY, 2012, 11 (03) :369-383
[29]   Carvedilol abrogates hypoxia-induced oxidative stress and neuroinflammation in microglial BV2 cells [J].
Gao, Xiujuan ;
Wu, Bin ;
Fu, Zhijian ;
Zhang, Zongwang ;
Xu, Guangjun .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2017, 814 :144-150
[30]   Portal Hypertensive Bleeding in Cirrhosis: Risk Stratification, Diagnosis, and Management: 2016 Practice Guidance by the American Association for the Study of Liver Diseases [J].
Garcia-Tsao, Guadalupe ;
Abraldes, Juan G. ;
Berzigotti, Annalisa ;
Bosch, Jaime .
HEPATOLOGY, 2017, 65 (01) :310-335