Role of Non-Selective Beta Blockers in Hepatocellular Carcinoma: An Analysis in Patients with Cirrhosis and Portal Hypertension
Keywords:
cirrhosis, portal hypertension, liver cancer/hepatocellular carcinoma, non-selective B blockersAbstract
There are many different biochemical processes responsible for the hepatocelluar carcinoma (HCC) development that can be targeted for the prevention or halt progression of the HCC. Non-selective beta-blockers (NSBB) affects a multitude of intracellular biochemical and signaling pathways involved in carcinogenesis. Aim: To determine if NSBB may be protective for HCC in patients with cirrhosis and portal hypertension. Methods: We retrospectively enrolled 200 patients from medical records diagnosed with cirrhosis and portal hypertension between January 2001 and December 2013. Eighteen patients were excluded (taking selective beta-blocker and/or unavailable medical records). The etiology of cirrhosis, use of NSBB, demographics and the presence of HCC was collected. Result: There were 140 males and 42 females. The mean age for portal hypertension with cirrhosis without HCC was 53.5 ± 11.4 & with HCC was 62.2 ± 9.5 years. Univariate analysis of the association of NSBB with HCC yielded OR = 0. 11 (95% CI: 0.04 to 0.25); p < 0.0001, suggesting a protective effect of NSBB. Multivariable analysis suggests virtually no change when the Odds ratio (OR) was adjusted for diabetes mellitus (DM), alcohol use, Hepatitis B virus (HBV) status, Black race and age ≥ 53. There was a slight increase in the OR adjusted for statin use. Conclusion: This study highlights association of NSBB use in the patients with liver cirrhosis and portal hypertension for prevention of HCC.References
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69-90.
El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118-1127.
Cejas P, Casado E, Belda-Iniesta C, et al. Implications of oxidative stress and cell membrane lipid peroxidation in human cancer (Spain). Cancer Causes Control. 2004;15:707-719.
Wang W, Sun Q, Wu Z, et al. Mitochondrial dysfunction-related genes in hepatocellular carcinoma. Front Biosci (Landmark Ed). 2013;18:1141-1149.
Nkontchou G, Aout M, Mahmoudi A, et al. Effect of long-term propranolol treatment on hepatocellular carcinoma incidence in patients with HCV-associated cirrhosis. Cancer Prev Res (Phila). 2012;5:1007-1014.
Mise M, Arii S, Higashituji H, et al. Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor. Hepatology. 1996;23:455-464.
Armaiz-Pena GN, Cole SW, Lutgendorf SK, Sood AK. Neuroendocrine influences on cancer progression. Brain Behav Immun. 2013;30:S19-S25.
Dapito DH, Mencin A, Gwak G-Y, et al. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 2012;21:504-516.
Pearce PC, Hawkey CM, Symons C, Olsen EG. The importance of membrane stabilization in protecting the developing rat myocardium from the actions of triac. Am J Cardiovasc Pathol. 1988;2:173-179.
Mansuy P, Mougenot N, Ramirez-Gil JF, et al. Effects of prolonged propranolol treatment on left ventricular remodeling and oxidative stress after myocardial infarction in rats. J Cardiovasc Pharmacol. 2000;35:8006-8013.
Fiskum G, Starkov A, Polster BM, Chinopoulos C. Mitochondrial mechanisms of neural cell death and neuroprotective interventions in Parkinson’s disease. Ann N Y Acad Sci. 2006;991:111-119.
Annabi B, Lachambre M-P, Plouffe K, Moumdjian R, Béliveau R. Propranolol adrenergic blockade inhibits human brain endothelial cells tubulogenesis and matrix metalloproteinase-9 secretion. Pharmacol Res. 2009;60:438-445.
Sommers Smith SK, Smith DM. Beta blockade induces apoptosis in cultured capillary endothelial cells. In Vitro Cell Dev Biol Anim. 2002;38:298-304.
Sozzani S, Agwu DE, McCall CE, et al. Propranolol, a phosphatidate phosphohydrolase inhibitor, also inhibits protein kinase C. J Biol Chem. 1992;267:20481-20488.
Zhang D, Yong Ma Q, Hu H-T, Zhang M. β 2 -adrenergic antagonists suppress pancreatic cancer cell invasion by inhibiting CREB, NF-κB and AP-1. Cancer Biol Ther. 2010;10:19-29.
Yang E V, Sood AK, Chen M, et al. Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells. Cancer Res. 2006;66:10357-10364.
Zanetti AR, Van Damme P, Shouval D. The global impact of vaccination against hepatitis B: a historical overview. Vaccine. 2008;26:6266-6273.
Sung JJY, Tsoi KKF, Wong VWS, Li KCT, Chan HLY. Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008;28:1067-1077.
Singal AK, Singh A, Jaganmohan S, et al. Antiviral therapy reduces risk of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis. Clin Gastroenterol Hepatol. 2010;8:192-199.
Singal AG, Volk ML, Jensen D, Di Bisceglie AM, Schoenfeld PS. A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus. Clin Gastroenterol Hepatol. 2010;8:280-288, 288.e1.
Tsan Y-T, Lee C-H, Ho W-C, Lin M-H, Wang J-D, Chen P-C. Statins and the risk of hepatocellular carcinoma in patients with hepatitis C virus infection. J Clin Oncol. 2013;31:1514-1521.
Tsan Y-T, Lee C-H, Wang J-D, Chen P-C. Statins and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection. J Clin Oncol. 2012;30:623-630.
Singal AK, Singh A, Jaganmohan S, et al. Antiviral therapy reduces risk of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis. Clin Gastroenterol Hepatol. 2010;8:192-199.
Kim TW, Kim HJ, Chon CU, et al. Is there any vindication for low dose nonselective β-blocker medication in patients with liver cirrhosis? Clin Mol Hepatol. 2012;18:203-212.
Krag A, Wiest R, Albillos A, Gluud LL. The window hypothesis: haemodynamic and non-haemodynamic effects of β-blockers improve survival of patients with cirrhosis during a window in the disease. Gut. 2012;61:967-969.
Senzolo M, Cholongitas E, Burra P, et al. beta-Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. Liver Int. 2009;29:1189-1193.
Bangalore S, Kumar S, Kjeldsen SE, et al. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials. Lancet Oncol. 2011;12:65-82.
Diaz ES, Karlan BY, Li AJ. Impact of beta blockers on epithelial ovarian cancer survival. Gynecol Oncol. 2012;127:375-378.
Chim H, Armijo BS, Miller E, Gliniak C, Serret MA, Gosain AK. Propranolol induces regression of hemangioma cells through HIF-1α-mediated inhibition of VEGF-A. Ann Surg. 2012;256:146-156.
El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118-1127.
Cejas P, Casado E, Belda-Iniesta C, et al. Implications of oxidative stress and cell membrane lipid peroxidation in human cancer (Spain). Cancer Causes Control. 2004;15:707-719.
Wang W, Sun Q, Wu Z, et al. Mitochondrial dysfunction-related genes in hepatocellular carcinoma. Front Biosci (Landmark Ed). 2013;18:1141-1149.
Nkontchou G, Aout M, Mahmoudi A, et al. Effect of long-term propranolol treatment on hepatocellular carcinoma incidence in patients with HCV-associated cirrhosis. Cancer Prev Res (Phila). 2012;5:1007-1014.
Mise M, Arii S, Higashituji H, et al. Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor. Hepatology. 1996;23:455-464.
Armaiz-Pena GN, Cole SW, Lutgendorf SK, Sood AK. Neuroendocrine influences on cancer progression. Brain Behav Immun. 2013;30:S19-S25.
Dapito DH, Mencin A, Gwak G-Y, et al. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 2012;21:504-516.
Pearce PC, Hawkey CM, Symons C, Olsen EG. The importance of membrane stabilization in protecting the developing rat myocardium from the actions of triac. Am J Cardiovasc Pathol. 1988;2:173-179.
Mansuy P, Mougenot N, Ramirez-Gil JF, et al. Effects of prolonged propranolol treatment on left ventricular remodeling and oxidative stress after myocardial infarction in rats. J Cardiovasc Pharmacol. 2000;35:8006-8013.
Fiskum G, Starkov A, Polster BM, Chinopoulos C. Mitochondrial mechanisms of neural cell death and neuroprotective interventions in Parkinson’s disease. Ann N Y Acad Sci. 2006;991:111-119.
Annabi B, Lachambre M-P, Plouffe K, Moumdjian R, Béliveau R. Propranolol adrenergic blockade inhibits human brain endothelial cells tubulogenesis and matrix metalloproteinase-9 secretion. Pharmacol Res. 2009;60:438-445.
Sommers Smith SK, Smith DM. Beta blockade induces apoptosis in cultured capillary endothelial cells. In Vitro Cell Dev Biol Anim. 2002;38:298-304.
Sozzani S, Agwu DE, McCall CE, et al. Propranolol, a phosphatidate phosphohydrolase inhibitor, also inhibits protein kinase C. J Biol Chem. 1992;267:20481-20488.
Zhang D, Yong Ma Q, Hu H-T, Zhang M. β 2 -adrenergic antagonists suppress pancreatic cancer cell invasion by inhibiting CREB, NF-κB and AP-1. Cancer Biol Ther. 2010;10:19-29.
Yang E V, Sood AK, Chen M, et al. Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells. Cancer Res. 2006;66:10357-10364.
Zanetti AR, Van Damme P, Shouval D. The global impact of vaccination against hepatitis B: a historical overview. Vaccine. 2008;26:6266-6273.
Sung JJY, Tsoi KKF, Wong VWS, Li KCT, Chan HLY. Meta-analysis: Treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2008;28:1067-1077.
Singal AK, Singh A, Jaganmohan S, et al. Antiviral therapy reduces risk of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis. Clin Gastroenterol Hepatol. 2010;8:192-199.
Singal AG, Volk ML, Jensen D, Di Bisceglie AM, Schoenfeld PS. A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus. Clin Gastroenterol Hepatol. 2010;8:280-288, 288.e1.
Tsan Y-T, Lee C-H, Ho W-C, Lin M-H, Wang J-D, Chen P-C. Statins and the risk of hepatocellular carcinoma in patients with hepatitis C virus infection. J Clin Oncol. 2013;31:1514-1521.
Tsan Y-T, Lee C-H, Wang J-D, Chen P-C. Statins and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection. J Clin Oncol. 2012;30:623-630.
Singal AK, Singh A, Jaganmohan S, et al. Antiviral therapy reduces risk of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis. Clin Gastroenterol Hepatol. 2010;8:192-199.
Kim TW, Kim HJ, Chon CU, et al. Is there any vindication for low dose nonselective β-blocker medication in patients with liver cirrhosis? Clin Mol Hepatol. 2012;18:203-212.
Krag A, Wiest R, Albillos A, Gluud LL. The window hypothesis: haemodynamic and non-haemodynamic effects of β-blockers improve survival of patients with cirrhosis during a window in the disease. Gut. 2012;61:967-969.
Senzolo M, Cholongitas E, Burra P, et al. beta-Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. Liver Int. 2009;29:1189-1193.
Bangalore S, Kumar S, Kjeldsen SE, et al. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324,168 participants from randomised trials. Lancet Oncol. 2011;12:65-82.
Diaz ES, Karlan BY, Li AJ. Impact of beta blockers on epithelial ovarian cancer survival. Gynecol Oncol. 2012;127:375-378.
Chim H, Armijo BS, Miller E, Gliniak C, Serret MA, Gosain AK. Propranolol induces regression of hemangioma cells through HIF-1α-mediated inhibition of VEGF-A. Ann Surg. 2012;256:146-156.
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Published
2016-01-15
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Patel, H., Kumar, A., Shah, N., Eris, E., Maroules, M., Baddoura, W. J., & DeBari, V. A. (2016). Role of Non-Selective Beta Blockers in Hepatocellular Carcinoma: An Analysis in Patients with Cirrhosis and Portal Hypertension. North American Journal of Medicine and Science, 8(3). Retrieved from https://najms.com/index.php/najms/article/view/71
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