RECONSIDERING STATINS-CURRENT VIEW

Authors

  • Cristina CIJEVSCHI PRELIPCEAN “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania
  • Mihaela DRANGA “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania
  • Catalina MIHAI “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania

Abstract

RECONSIDERING STATINS-CURRENT VIEW (Abstract): Statins are widely used in daily clinical practice for the management of dyslipidemia. There are numerous studies that have shown a pleiotropic effect of statins in chronic liver diseases. They increase nitric oxide synthesis, restore endothelial cell function and, by that, increase the number of progenitor endothelial cells which improve endothelial function. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension by reduction of hepatic vascular resistance without adverse effects on systemic circulation and with an excellent safety profile. Simvastatin addition to standard therapy in patients with cirrhosis who recover from an acute variceal bleeding episode improves survivability. Statins modulate intrahepatic vascular tone and by that improve liver function and lack of significant hepatotoxic effects. Statins inhibit protease pathway activation, exert anti-inflammatory and immunomodulatory effects, modifying the cell activation cascade. Due to all these mechanisms, statins have antineoplastic effects.

Author Biographies

  • Cristina CIJEVSCHI PRELIPCEAN, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania

    Faculty of Medicine
    Department of Medical Specialties (I)
    Institute of Gastroenterology and Hepatology Iasi

  • Mihaela DRANGA, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania

    Faculty of Medicine
    Department of Medical Specialties (I)
    Institute of Gastroenterology and Hepatology Iasi

  • Catalina MIHAI, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania

    Faculty of Medicine
    Department of Medical Specialties (I)
    Institute of Gastroenterology and Hepatology Iasi

References

1. Imprialos KP, Stavropoulos K, Doumas M, et al. The potential role of statins in treating liver disease. Expert Rev Gastroenterol Hepatol 2018; 12(4): 331-339.
2. Kim RG, Loomba R, Prokop LJ, Singh. S. Statin Use and Risk of Cirrhosis and Related Complications in Patients with Chronic Liver Diseases: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2017;15: 1521-1530.
3. Cijevschi Prelipcean C, Mihai C, Gogalniceanu P, Mihai B. Extrahepatic complications of chronic cholestasis: current diagnosis and treatment. Rev. Med. Chir. Soc. Med. Nat. 2012; 116(2): 490-499.
4. McGirt MJ, Lynch JR, Parra A, et al. Simvastatin increases endothelial nitric oxide synthase and ameliorates cerebral vasospasm resulting from subarachnoid hemorrhage. Stroke 2002; 33: 2950-2956.
5. Badescu C, Rezus E, Badescu L, Dima N, Rezus C. New drugs for lowering LDL-cholesterol. Rev. Med. Chir. Soc. Med. Nat. 2016; 120(3): 485-490.
6. Kalinowski L, Dobrucki LW, Brovkovych V, et al. Increased nitric oxide bioavailability in endothelial cells contributes to the pleiotropic effect of cerivastatin. Circulation 2002; 105 :933-938.
7. Mura VL, Pasarin M, Meireles CZ, et al. Effects of simvastatin administration on rodents with lipo-polysaccharide-induced liver microvascular dysfunction. Hepatology 2013; 57: 1172-1181.
8. Marrone G, Maeso-Diaz R, Garcia-Cardena G, et al. KLF2 exerts antifibrotic and vasoprotective effects in cirrhotic rat livers: behind the molecular mechanisms of statins. Gut 2015; 64: 1434-1443.
9. Huang Y-W, Lee C-L, Yang S-S, et al. Statins reduce the risk of cirrhosis and its decompensation in chronic hepatitis B patients: a nationwide cohort study. Am J Gastroenterol 2016; 111:976–985.
10. Kumar S, Grace ND, Qamar AA. Statin use in patients with cirrhosis: a retrospective cohort study. Dig Dis Sci 2014; 59: 1958-1965.
11. Abraldes JG, Tarantino I, Turnes J, et al. Hemodynamic response to pharmacological treatment of portal hypertension and long term prognosis of cirrhosis. Hepatology 2003; 37: 902-908.
12. D’Amico G, Garcia-Pagan JC, Luca A, et al. Hepatic vein pressure gradient reduction and prevention of variceal bleeding in cirrhosis: a systematic review. Gastroenterology 2006; 131: 1611-1624.
13. Abraldes JG, Rodriguez-Vilarrupla A, Graupera M, et al. Simvastatin treatment improves liver sinus-oidal endothelial dysfunction in CCl4 cirrhotic rats. J Hepatol 2007; 46: 1040-1046.
14. Trebicka J, Hennenberg M, Laleman W, et al. Atorvastatin lowers portal pressure in cirrhotic rats by inhibition of RhoA/Rho-kinase and activation of endothelial nitric oxide synthase. Hepatology 2007; 46: 242-253.
15. Abraldes JG, Albillos A, Banares R, et al. Simvastatin Lowers Portal Pressure in Patients with Cirrhosis and Portal Hypertension: A Randomized Controlled Trial Gastroenterology 2009; 136: 1651-1658.
16. Pollo-Flores P, Soldan M, Santos UC,et al. Three months of simvastatin therapy vs. placebo for severe portal hypertension in cirrhosis: A randomized controlled trial. Dig Liv Dis 2015; 47: 957-963.
17. Abraldes JG, Villanueva C, Aracil C, Turnes J, Hernandez-Guerra M, Genesca J, et al. Addition of simvastatin to standard therapy for the prevention of variceal rebleeding does not reduce rebleeding but increases survival in patients with cirrhosis. Gastroenterology 2016; 150: 1160-1170.
18. Mohanty A, Tate JP, Garcia-Tsao G. Statins Are Associated with a Decreased Risk of Decompensation and Death in Veterans with Hepatitis C–Related Compensated Cirrhosis. Gastroenterology 2016; 150: 430-440.
19. Motzkus-Feagans C, Pakyz AL, Ratliff SM, et al. Statin use and infections in Veterans with cirrhosis. Aliment Pharmacol Ther 2013; 38: 611-618.
20. Singh S, Singh PP, Singh AG, et al. Statins Are Associated with a Reduced Risk of Hepatocellular Cancer: A Systematic Review and Meta-analysis. Gastroenterology 2013; 144: 323-332.
21. Tsan YT, Lee CH, Wang JD, et al. Statins and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection. J Clin Oncol 2012; 30: 623-630.
22. El-Serag HB, Johnson ML, Hachem C, et al. Statins are associated with a reduced risk of hepatocellular carcinoma in a large cohort of patients with diabetes. Gastroenterology 2009; 136: 1601-1608.
23. Weis M, Heeschen C, Glassford AJ, et al. Statins have biphasic effects on angiogenesis. Circulation 2002; 105: 739-745.
24. Hamelin BA, Turgeon J. Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol Sci 1998; 19: 26-37.

Additional Files

Published

2019-03-29

Issue

Vol. 123 No. 1 (2019): The Medical-Surgical Journal

Section

INTERNAL MEDICINE - PEDIATRICS

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