{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:01:09Z","timestamp":1787162469133,"version":"build-2736575974"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Hepatocellular carcinoma (HCC) is a serious complication of cirrhosis. Currently, non-selective beta-blockers (NSBBs) are commonly used to treat portal hypertension in patients with cirrhosis. The latest research shows that NSBBs can induce apoptosis and S-phase arrest in liver cancer cells and inhibit the development of hepatic vascular endothelial cells, which may be effective in preventing HCC in cirrhosis patients.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Aim:<\/jats:bold>\n                    To determine the relationship between different NSBBs and HCC incidence in patients with cirrhosis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    We searched the Cochrane database, MEDLINE, EMBASE, PubMed, and Web of Science. Cohort studies, case\u2012control studies, and randomized controlled trials were included if they involved cirrhosis patients who were divided into an experimental group using NSBBs and a control group with any intervention. Based on heterogeneity, we calculated odds ratio (OR) and 95% confidence interval (CI) using random-effect models. We also conducted subgroup analysis to explore the source of heterogeneity. Sensitivity analysis and publication bias detection were performed.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    A total of 47 studies included 38 reporting HCC incidence, 26 reporting HCC-related mortality, and 39 reporting overall mortality. The HCC incidence between the experimental group and the control group was OR = 0.87 (0.69 and 1.10),\n                    <jats:italic>p<\/jats:italic>\n                    = 0.000, and I\n                    <jats:sup>2<\/jats:sup>\n                    = 81.8%. There was no significant association between propranolol (OR = 0.94 and 95%CI 0.62\u20131.44) or timolol (OR = 1.32 and 95%CI 0.44\u20133.95) and HCC incidence, while the risk of HCC decreased by 26% and 38% with nadolol (OR = 0.74 and 95%CI 0.64\u20130.86) and carvedilol (OR = 0.62 and 95%CI 0.52\u20130.74), respectively.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    Different types of NSBB have different effects on the incidence of patients with cirrhosis of the liver, where nadolol and carvedilol can reduce the risk. Also, the effect of NSBBs may vary in ethnicity. Propranolol can reduce HCC incidence in Europe and America.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Systematic Review Registration:<\/jats:bold>\n                    identifier\n                    <jats:ext-link>https:\/\/CRD42023434175<\/jats:ext-link>\n                    ,\n                    <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.3389\/fphar.2023.1216059","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T03:57:43Z","timestamp":1689739063000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Non-selective beta-blockers and the incidence of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis"],"prefix":"10.3389","volume":"14","author":[{"given":"Xinyi","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zimo","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1097\/CAD.0b013e32832bd1e3","article-title":"Prevention of pancreatic cancer by the beta-blocker propranolol","volume":"20","author":"Al-Wadei","year":"2009","journal-title":"Anti-cancer drugs"},{"key":"B2","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0168-8278(88)80480-X","article-title":"Propranolol or endoscopic sclerotherapy in the prevention of recurrence of variceal bleeding. A prospective, randomized controlled trial","volume":"7","author":"Alexandrino","year":"1988","journal-title":"J. hepatology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1016\/0016-5085(93)90356-h","article-title":"Isosorbide-5-mononitrate versus propranolol in the prevention of first bleeding in cirrhosis","volume":"104","author":"Angelico","year":"1993","journal-title":"Gastroenterology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1053\/jhep.1997.v25.pm0008985266","article-title":"Beta-adrenergic antagonists in the prevention of gastrointestinal rebleeding in patients with cirrhosis: A meta-analysis","volume":"25","author":"Bernard","year":"1997","journal-title":"Hepatol. Baltim. Md)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/S0168-8278(02)00174-5","article-title":"Nadolol is superior to isosorbide mononitrate for the prevention of the first variceal bleeding in cirrhotic patients with ascites","volume":"37","author":"Borroni","year":"2002","journal-title":"J. hepatology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1007\/s10238-022-00842-z","article-title":"Beta-adrenergic receptor blockers and hepatocellular carcinoma survival: A systemic review and meta-analysis","volume":"23","author":"Chang","year":"2022","journal-title":"Clin. Exp. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"108","DOI":"10.4103\/sjg.sjg_586_21","article-title":"Propranolol use in patients with cirrhosis and refractory ascites: A nationwide study","volume":"28","author":"Chen","year":"2022","journal-title":"Saudi J. Gastroenterology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1097\/SLA.0b013e318254ce7a","article-title":"Propranolol induces regression of hemangioma cells through HIF-1\u03b1-mediated inhibition of VEGF-A","volume":"256","author":"Chim","year":"2012","journal-title":"Ann. Surg."},{"key":"B9","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1111\/j.1440-1746.2005.03982.x","article-title":"Spontaneous bacterial peritonitis in cirrhotic patients: Is prophylactic propranolol therapy beneficial?","volume":"21","author":"Cholongitas","year":"2006","journal-title":"J. Gastroenterology Hepatology Aust."},{"key":"B10","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1002\/hep.1840130517","article-title":"Propranolol in the prevention of the first hemorrhage from esophagogastric varices: A multicenter, randomized clinical trial","volume":"13","author":"Conn","year":"1991","journal-title":"Hepatol. Baltim. Md)"},{"key":"B11","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/j.jhep.2015.05.022","article-title":"Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension","volume":"63","author":"de Franchis","year":"2015","journal-title":"J. hepatology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1002\/hep.20584","article-title":"Variceal ligation plus nadolol compared with ligation for prophylaxis of variceal rebleeding: A multicenter trial","volume":"41","author":"De La Pe\u00f1a","year":"2005","journal-title":"Hepatol. Baltim. Md)"},{"key":"B13","doi-asserted-by":"publisher","first-page":"628","DOI":"10.4253\/wjge.v13.i12.628","article-title":"Primary prophylaxis of variceal bleeding in patients with cirrhosis: A comparison of different strategies","volume":"13","author":"de Mattos \u00c2","year":"2021","journal-title":"World J. Gastrointest. Endosc."},{"key":"B14","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1002\/j.1552-4604.1977.tb04609.x","article-title":"Metabolic studies in patients with nadolol: Oral and intravenous administration","volume":"17","author":"Dreyfuss","year":"1977","journal-title":"J. Clin. Pharmacol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1053\/jhep.2002.30418","article-title":"TIPS versus drug therapy in preventing variceal rebleeding in advanced cirrhosis: A randomized controlled trial","volume":"35","author":"Escorsell","year":"2002","journal-title":"Hepatol. Baltim. Md)"},{"key":"B16","doi-asserted-by":"publisher","first-page":"3485","DOI":"10.1002\/cncr.28832","article-title":"Risk prediction of hepatocellular carcinoma in patients with cirrhosis: The ADRESS-HCC risk model","volume":"120","author":"Flemming","year":"2014","journal-title":"Cancer"},{"key":"B17","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.jhep.2019.10.002","article-title":"Impact of cardiac function, refractory ascites and beta blockers on the outcome of patients with cirrhosis listed for liver transplantation","volume":"72","author":"Giannelli","year":"2020","journal-title":"J. hepatology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.1111\/liv.13890","article-title":"Treatment with non-selective beta-blockers affects the systemic inflammatory response to bacterial DNA in patients with cirrhosis","volume":"38","author":"Gimenez","year":"2018","journal-title":"Liver Int."},{"key":"B19","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1097\/00042737-200601000-00009","article-title":"Pharmacologic treatment of portal hypertension in the prevention of community-acquired spontaneous bacterial peritonitis","volume":"18","author":"Gonzalez-Suarez","year":"2006","journal-title":"Eur. J. Gastroenterology Hepatology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.1056\/NEJMoa044456","article-title":"Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis","volume":"353","author":"Groszmann","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1053\/j.semdp.2016.12.011","article-title":"The diagnosis and treatment of hepatocellular carcinoma","volume":"34","author":"Hartke","year":"2017","journal-title":"Seminars diagnostic pathology"},{"key":"B22","first-page":"402","article-title":"Nadolol can prevent the first variceal bleeding in cirrhotics. A prospective randomized study","volume":"94","author":"Ideo","year":"1987","journal-title":"Policlin. - Sezione Chir."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.3109\/13880209.2014.892513","article-title":"beta-Adrenoreceptor antagonists reduce cancer cell proliferation, invasion, and migration","volume":"52","author":"I\u015feri","year":"2014","journal-title":"Pharm. Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1007\/s12072-021-10160-3","article-title":"The longitudinal outcomes of applying non-selective beta-blockers in portal hypertension: Real-world multicenter study","volume":"15","author":"Kang","year":"2021","journal-title":"Hepatol. Int."},{"key":"B25","doi-asserted-by":"publisher","first-page":"203","DOI":"10.3350\/cmh.2012.18.2.203","article-title":"Is there any vindication for low dose nonselective \u03b2-blocker medication in patients with liver cirrhosis?","volume":"18","author":"Kim","year":"2012","journal-title":"Clin. Mol. hepatology"},{"key":"B26","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1053\/j.gastro.2018.08.065","article-title":"Epidemiology and management of hepatocellular carcinoma","volume":"156","author":"Kulik","year":"2019","journal-title":"Gastroenterology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1111\/j.1440-1746.2005.04071.x","article-title":"Endoscopic variceal ligation versus propranolol in prophylaxis of first variceal bleeding in patients with cirrhosis","volume":"21","author":"Lay","year":"2006","journal-title":"J. Gastroenterology Hepatology Aust."},{"key":"B28","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/s0140-6736(80)90063-x","article-title":"Propranolol--a medical treatment for portal hypertension?","volume":"2","author":"Lebrec","year":"1980","journal-title":"Lancet (London, Engl."},{"key":"B29","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/S0168-8278(88)80515-4","article-title":"Nadolol for prophylaxis of gastrointestinal bleeding in patients with cirrhosis. A randomized trial","volume":"7","author":"Lebrec","year":"1988","journal-title":"J. hepatology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1097\/MEG.0000000000001511","article-title":"Low dose of propranolol treatment is associated with better survival in cirrhotic patients with hepatic encephalopathy","volume":"32","author":"Lee","year":"2020","journal-title":"Eur. J. Gastroenterology Hepatology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"S392","DOI":"10.1016\/S0168-8278(14)61111-9","article-title":"Non-selective beta-blockers are associated with improved survival in patients with ascites listed for liver transplantation","volume":"60","author":"Leithead","year":"2014","journal-title":"J. hepatology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.3892\/or_00001032","article-title":"The \u03b2-adrenoceptor antagonist, propranolol, induces human gastric cancer cell apoptosis and cell cycle arrest via inhibiting nuclear factor \u03baB signaling","volume":"24","author":"Liao","year":"2010","journal-title":"Oncol. Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/S0016-5107(03)02819-0","article-title":"Endoscopic ligation vs. nadolol in the prevention of first variceal bleeding in patients with cirrhosis","volume":"59","author":"Lo","year":"2004","journal-title":"Gastrointest. Endosc."},{"key":"B34","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1053\/jhep.2000.16236","article-title":"Endoscopic variceal ligation plus nadolol and sucralfate compared with ligation alone for the prevention of variceal rebleeding: A prospective, randomized trial","volume":"32","author":"Lo","year":"2000","journal-title":"Hepatol. Baltim. Md)"},{"key":"B35","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1002\/hep.22358","article-title":"Improved survival in patients receiving medical therapy as compared with banding ligation for the prevention of esophageal variceal rebleeding","volume":"48","author":"Lo Iacono","year":"2008","journal-title":"Hepatology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1148\/radiol.15141252","article-title":"Advanced cirrhosis combined with portal vein thrombosis: A randomized trial of TIPS versus endoscopic band ligation plus propranolol for the prevention of recurrent esophageal variceal bleeding","volume":"276","author":"Luo","year":"2015","journal-title":"Radiology"},{"key":"B37","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1136\/gutjnl-2017-314634","article-title":"Covered TIPS versus endoscopic band ligation plus propranolol for the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis: A randomised controlled trial","volume":"67","author":"Lv","year":"2017","journal-title":"Gut"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1016\/j.jhep.2016.01.031","article-title":"Keep the sick from harm in spontaneous bacterial peritonitis: Dose of beta blockers matters","volume":"64","author":"Madsen","year":"2016","journal-title":"J. hepatology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.1053\/j.gastro.2014.03.005","article-title":"Nonselective \u03b2 blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis","volume":"146","author":"Mandorfer","year":"2014","journal-title":"Gastroenterology"},{"key":"B40","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1080\/00365521.2020.1762919","article-title":"Beta-adrenergic receptor blockers and liver cancer mortality in a national cohort of hepatocellular carcinoma patients","volume":"55","author":"Marsdottir","year":"2020","journal-title":"Scand. J. gastroenterology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/0163-7258(90)90092-g","article-title":"Beta-blockers and central nervous system side effects","volume":"46","author":"McAinsh","year":"1990","journal-title":"Pharmacol. Ther."},{"key":"B42","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1111\/apt.16189","article-title":"Carvedilol is associated with improved survival in patients with cirrhosis: A long-term follow-up study","volume":"53","author":"McDowell","year":"2021","journal-title":"Alimentary Pharmacol. Ther."},{"key":"B43","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1053\/j.gastro.2004.05.004","article-title":"A placebo-controlled clinical trial of nadolol in the prophylaxis of growth of small esophageal varices in cirrhosis","volume":"127","author":"Merkel","year":"2004","journal-title":"Gastroenterology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"84","DOI":"10.5114\/ceh.2022.114271","article-title":"Prophylactic cyanoacrylate injection for gastric extension of esophageal varices: A randomized controlled trial","volume":"8","author":"Metwally","year":"2022","journal-title":"Clin. Exp. Hepatology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"S1085","DOI":"10.1016\/s0016-5085(16)33663-0","article-title":"Sa1649 non-selective beta blocker use is associated with improved short-term survival in patients referred for liver transplantation","volume":"150","author":"Ngwa","year":"2016","journal-title":"Gastroenterology"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1158\/1940-6207.CAPR-11-0450","article-title":"Effect of long-term propranolol treatment on hepatocellular carcinoma incidence in patients with HCV-associated cirrhosis","volume":"5","author":"Nkontchou","year":"2012","journal-title":"Cancer Prev. Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"52","DOI":"10.2165\/00003495-198900372-00011","article-title":"Propranolol in the primary prevention of upper gastrointestinal tract haemorrhage in patients with cirrhosis of the liver and oesophageal varices","volume":"37","author":"Pascal","year":"1989","journal-title":"Drugs"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1053\/gast.2002.35955","article-title":"A randomized, controlled trial of medical therapy versus endoscopic ligation for the prevention of variceal rebleeding in patients with cirrhosis","volume":"123","author":"Patch","year":"2002","journal-title":"Gastroenterology"},{"key":"B49","doi-asserted-by":"publisher","first-page":"628","DOI":"10.18632\/oncotarget.101009","article-title":"Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival","volume":"1","author":"Powe","year":"2010","journal-title":"Oncotarget"},{"key":"B50","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.jceh.2021.09.008","article-title":"Clinical implications, evaluation, and management of hyponatremia in cirrhosis","volume":"12","author":"Praharaj","year":"2022","journal-title":"J. Clin. Exp. hepatology"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1016\/j.jceh.2022.04.021","article-title":"Overview of complications in cirrhosis","volume":"12","author":"Premkumar","year":"2022","journal-title":"J. Clin. Exp. hepatology"},{"key":"B52","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1097\/MCG.0000000000001219","article-title":"Carvedilol combined with ivabradine improves left ventricular diastolic dysfunction, clinical progression, and survival in cirrhosis","volume":"54","author":"Premkumar","year":"2020","journal-title":"J. Clin. gastroenterology"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1097\/00042737-200510000-00016","article-title":"Endoscopic variceal ligation vs. propranolol for prevention of first variceal bleeding: A randomized controlled trial","volume":"17","author":"Psilopoulos","year":"2005","journal-title":"Eur. J. Gastroenterology Hepatology"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1053\/gast.1997.v113.pm9352865","article-title":"Transjugular intrahepatic portosystemic stent shunt versus sclerotherapy plus propranolol for variceal rebleeding","volume":"113","author":"Sauer","year":"1997","journal-title":"Gastroenterology"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1080\/00365521.2017.1329456","article-title":"Non-selective beta-blocker treatment does not impact on kidney function in cirrhotic patients with varices","volume":"52","author":"Scheiner","year":"2017","journal-title":"Scand. J. gastroenterology"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1111\/j.1478-3231.2009.02038.x","article-title":"beta-Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis","volume":"29","author":"Senzolo","year":"2009","journal-title":"Liver Int. official J. Int. Assoc. Study Liver"},{"key":"B57","doi-asserted-by":"publisher","first-page":"2436","DOI":"10.1111\/j.1572-0241.2006.00742_5.x","article-title":"The low incidence of bacterial infections could be a protective factor against variceal bleeding per se in hemodynamic responders to propranolol","volume":"101","author":"Senzolo","year":"2006","journal-title":"Am. J. gastroenterology"},{"key":"B58","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.jhep.2011.01.034","article-title":"Beta-blockers cause paracentesis-induced circulatory dysfunction in patients with cirrhosis and refractory ascites: A cross-over study","volume":"55","author":"Serst\u00e9","year":"2011","journal-title":"J. hepatology"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1002\/hep.23775","article-title":"Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites","volume":"52","author":"Serst\u00e9","year":"2010","journal-title":"Hepatol. Baltim. Md)"},{"key":"B60","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA a cancer J. Clin."},{"key":"B61","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1007\/s12072-022-10361-4","article-title":"Propranolol vs. band ligation for primary prophylaxis of variceal hemorrhage in cirrhotic patients with ascites: A randomized controlled trial","volume":"16","author":"Singh","year":"2022","journal-title":"Hepatol. Int."},{"key":"B62","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.jhep.2017.02.005","article-title":"Exploring the potential chemoprophylactic role of carvedilol for hepatocellular carcinoma","volume":"18","author":"Sinha","year":"2022","journal-title":"Gastroenterology hepatology"},{"key":"B63","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.jhep.2017.02.005","article-title":"Carvedilol use is associated with improved survival in patients with liver cirrhosis and ascites","volume":"67","author":"Sinha","year":"2017","journal-title":"J. hepatology"},{"key":"B64","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1177\/1060028019886529","article-title":"Effect of nonselective \u03b2-blockers on mortality in patients with end-stage cirrhosis","volume":"54","author":"Snoga","year":"2020","journal-title":"Ann. Pharmacother."},{"key":"B65","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA a cancer J. Clin."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1016\/j.jhep.2020.05.011","article-title":"Non-selective beta-blockers impair global circulatory homeostasis and renal function in cirrhotic patients with refractory ascites","volume":"73","author":"T\u00e9llez","year":"2020","journal-title":"J. hepatology"},{"key":"B67","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1002\/hep.22600","article-title":"Improved survival with nonselective beta blockers","volume":"48","author":"Thalheimer","year":"2008","journal-title":"Hepatol. Baltim. Md)"},{"key":"B68","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.1111\/liv.12782","article-title":"Non-selective beta-blockers may reduce risk of hepatocellular carcinoma: A meta-analysis of randomized trials","volume":"35","author":"Thiele","year":"2015","journal-title":"Liver Int. official J. Int. Assoc. Study Liver"},{"key":"B69","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1002\/hep.23045","article-title":"Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed","volume":"50","author":"Tripathi","year":"2009","journal-title":"Hepatol. Baltim. Md)"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1016\/s0140-6736(18)31875-0","article-title":"\u03b2 blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): A randomised, double-blind, placebo-controlled, multicentre trial","volume":"393","author":"Villanueva","year":"2019","journal-title":"Lancet (London, Engl."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1056\/NEJM199606203342502","article-title":"Nadolol plus isosorbide mononitrate compared with sclerotherapy for the prevention of variceal rebleeding","volume":"334","author":"Villanueva","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"B72","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1056\/NEJMoa003223","article-title":"Endoscopic ligation compared with combined treatment with nadolol and isosorbide mononitrate to prevent recurrent variceal bleeding","volume":"345","author":"Villanueva","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1002\/hep.1840060602","article-title":"Propranolol for the prevention of recurrent variceal hemorrhage: A controlled trial","volume":"6","author":"Villeneuve","year":"1986","journal-title":"Hepatol. Baltim. Md)"},{"key":"B74","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1111\/apt.14265","article-title":"Impact of beta-blockers on cardiopulmonary exercise testing in patients with advanced liver disease","volume":"46","author":"Wallen","year":"2017","journal-title":"Alimentary Pharmacol. Ther."},{"key":"B75","doi-asserted-by":"publisher","first-page":"5213","DOI":"10.3892\/mmr.2018.8476","article-title":"Propranolol suppresses the proliferation and induces the apoptosis of liver cancer cells","volume":"17","author":"Wang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"B76","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1111\/apt.16490","article-title":"Nonselective beta-blockers are associated with a lower risk of hepatocellular carcinoma among cirrhotic patients in the United States","volume":"54","author":"Wijarnpreecha","year":"2021","journal-title":"Alimentary Pharmacol. Ther."},{"key":"B77","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/medicina56010014","article-title":"The role of non-selective \u03b2-blockers in compensated cirrhotic patients without major complications","volume":"56","author":"Yeh","year":"2019","journal-title":"Med. Kaunas. Lith."},{"key":"B78","doi-asserted-by":"publisher","first-page":"e18913","DOI":"10.1097\/MD.0000000000018913","article-title":"Propranolol plus endoscopic ligation for variceal bleeding in patients with significant ascites: Propensity score matching analysis","volume":"99","author":"Yoo","year":"2020","journal-title":"Med. (United States)"},{"key":"B79","doi-asserted-by":"publisher","first-page":"425","DOI":"10.3350\/cmh.2020.0234","article-title":"\u03b2-blockers in advanced cirrhosis: More friend than enemy","volume":"27","author":"Yoon","year":"2021","journal-title":"Clin. Mol. hepatology"},{"key":"B80","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1097\/cej.0000000000000192","article-title":"\u03b2-Blocker use and mortality in cancer patients: Systematic review and meta-analysis of observational studies","volume":"25","author":"Zhong","year":"2016","journal-title":"Eur. J. cancer Prev. official J. Eur. Cancer Prev. Organ. (ECP)"},{"key":"B81","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1056\/nejm198903023200905","article-title":"Racial differences in drug response. Altered sensitivity to and clearance of propranolol in men of Chinese descent as compared with American whites","volume":"320","author":"Zhou","year":"1989","journal-title":"N. Engl. J. Med."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1216059\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T03:57:46Z","timestamp":1689739066000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1216059\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,19]]},"references-count":81,"alternative-id":["10.3389\/fphar.2023.1216059"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1216059","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,19]]},"article-number":"1216059"}}