Simvastatin Lowers Portal Pressure in Patients With Cirrhosis and Portal Hypertension: A Randomized Controlled Trial

Gastroenterology

Volumn 136, Issue 5, 2009, Pages 1651-1658

  Abraldes, Juan G ^a,b   Albillos, Agustin ^b,c   Bañares, Rafael ^b,d   Turnes, Juan ^a,b   González, Rosario ^b,c   García Pagán, Juan Carlos ^a,b   Bosch, Jaime ^a,b  

^a Hospital Sant Joan de Déu   (Spain)

^b INSTITUTO DE SALUD CARLOS III   (Spain)

^c HOSPITAL RAMÓN Y CAJAL   (Spain)

^d HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑÓN   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

BETA ADRENERGIC RECEPTOR BLOCKING AGENT; PLACEBO; SIMVASTATIN;

ADULT; ARTICLE; ASCITES; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG EFFECT; DRUG POTENTIATION; DRUG SAFETY; FEMALE; HEMODYNAMICS; HUMAN; HYDROTHORAX; LIVER CIRRHOSIS; LIVER PERFUSION; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; MUSCLE WEAKNESS; PORTAL HYPERTENSION; PORTAL VEIN BLOOD PRESSURE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; THORACOCENTESIS;

EID: 65349094504     PISSN: 00165085     EISSN: None     Source Type: Journal    
DOI: 10.1053/j.gastro.2009.01.043     Document Type: Article

References (43)

1. Bosch J., Abraldes J.G., and Groszmann R.J. Current management of portal hypertension. J Hepatol 38 (2003) S54-S68
2. Vargas V., Rimola A., Casanovas T., et al. Applicability of liver transplantation in Catalonia at the end of the millennium. A prospective study of adult patient selection for liver transplantation. Transpl Int 16 (2003) 270-275
3. Abraldes J.G., Tarantino I., Turnes J., et al. Hemodynamic response to pharmacological treatment of portal hypertension and long-term prognosis of cirrhosis. Hepatology 37 (2003) 902-908
4. D'Amico G., Garcia-Pagan J.C., Luca A., et al. Hepatic vein pressure gradient reduction and prevention of variceal bleeding in cirrhosis: a systematic review. Gastroenterology 131 (2006) 1611-1624
5. Albillos A., Banares R., Gonzalez M., et al. Value of the hepatic venous pressure gradient to monitor drug therapy for portal hypertension: a meta-analysis. Am J Gastroenterol 102 (2007) 1116-1126
6. Gluud C., Brok J., Gong Y., et al. Hepatology may have problems with putative surrogate outcome measures. J Hepatol 46 (2007) 734-742
7. Ripoll C., Groszmann R., Garcia-Tsao G., et al. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology 133 (2007) 481-488
8. Feu F., Garcia-Pagan J.C., Bosch J., et al. Relation between portal pressure response to pharmacotherapy and risk of recurrent variceal haemorrhage in patients with cirrhosis. Lancet 346 (1995) 1056-1059
9. Thalheimer U., Bosch J., and Burroughs A.K. How to prevent varices from bleeding: shades of grey-the case for nonselective beta blockers. Gastroenterology 133 (2007) 2029-2036
10. Garcia-Tsao G., D'Amico G., Abraldes J.G., et al. Predictive models in portal hypertension. In: de Franchis R. (Ed). Proceedings of the fourth Baveno International Consensus Workshop on definitions, methodology and therapeutic strategies (2005), Blackwell-Science, Oxford 47-100
11. de Franchis R. Evolving consensus in portal hypertension report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 43 (2005) 167-176
12. Failli P., DeFranco R.M., Caligiuri A., et al. Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells. Gastroenterology 119 (2000) 479-492
13. Yu Q., Shao R., Qian H.S., et al. Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension. J Clin Invest 105 (2000) 741-748
14. Van de C.M., Omasta A., Janssens S., et al. In vivo gene transfer of endothelial nitric oxide synthase decreases portal pressure in anaesthetised carbon tetrachloride cirrhotic rats. Gut 51 (2002) 440-445
15. Morales-Ruiz M., Cejudo-Martn P., Fernandez-Varo G., et al. Transduction of the liver with activated Akt normalizes portal pressure in cirrhotic rats. Gastroenterology 125 (2003) 522-531
16. Salmeron J.M., Ruiz d.A., Gines A., et al. Renal effects of acute isosorbide-5-mononitrate administration in cirrhosis. Hepatology 17 (1993) 800-806
17. Wiest R., and Groszmann R.J. The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough. Hepatology 35 (2002) 478-491
18. Abraldes J.G., Rodriguez-Vilarrupla A., Graupera M., et al. Simvastatin treatment improves liver sinusoidal endothelial dysfunction in CCl4 cirrhotic rats. J Hepatol 46 (2007) 1040-1046
19. 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 46 (2007) 242-253
20. Zafra C., Abraldes J.G., Turnes J., et al. Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis. Gastroenterology 126 (2004) 749-755
21. Bosch J., Garcia-Pagan J.C., Berzigotti A., et al. Measurement of portal pressure and its role in the management of chronic liver disease. Semin Liver Dis 26 (2006) 348-362
22. Navasa M., Bosch J., Mastai R., et al. Measurement of hepatic blood flow, hepatic extraction and intrinsic clearance of indocyanine green in cirrhosis. Comparison of a non-invasive pharmacokinetic method with measurements using hepatic vein catheterization. Eur J Gastroenterol Hepatol 3 (1991) 305-312
23. Groszmann R.J., Garcia-Tsao G., Bosch J., et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med 353 (2005) 2254-2261
24. Bosch J., Mastai R., Kravetz D., et al. Effects of propranolol on azygos venous blood flow and hepatic and systemic hemodynamics in cirrhosis. Hepatology 4 (1984) 1200-1205
25. Banares R., Moitinho E., Matilla A., et al. Randomized comparison of long-term carvedilol and propranolol administration in the treatment of portal hypertension in cirrhosis. Hepatology 36 (2002) 1367-1373
26. Mastai R., Bosch J., Navasa M., et al. Effects of alpha-adrenergic stimulation and beta-adrenergic blockade on azygos blood flow and splanchnic haemodynamics in patients with cirrhosis. J Hepatol 4 (1987) 71-79
27. Kiszka-Kanowitz M., Henriksen J.H., Moller S., et al. Blood volume distribution in patients with cirrhosis: aspects of the dual-head gamma-camera technique. J Hepatol 35 (2001) 605-612
28. Huonker M., Schumacher Y.O., Ochs A., et al. Cardiac function and haemodynamics in alcoholic cirrhosis and effects of the transjugular intrahepatic portosystemic stent shunt. Gut 44 (1999) 743-748
29. Andreu V., Perello A., Moitinho E., et al. Total effective vascular compliance in patients with cirrhosis. Effects of propranolol. J Hepatol 36 (2002) 356-361
30. Barbare J.C., Poupon R.E., Jaillon P., et al. Intrinsic hepatic clearance and Child-Turcotte classification for assessment of liver function in cirrhosis. J Hepatol 1 (1985) 253-259
31. Caesar J., Shaldon S., Chiandussi L., et al. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci 21 (1961) 43-57
32. Lee J.S., Semela D., Iredale J., et al. Sinusoidal remodeling and angiogenesis: a new function for the liver-specific pericyte?. Hepatology 45 (2007) 817-825
33. DeLeve L.D., Wang X., Guo Y., et al. Sinusoidal endothelial cells prevent rat stellate cell activation and promote reversion to quiescence. Hepatology 48 (2008) 920-930
34. Garcia-Pagan J.C., Feu F., Bosch J., et al. Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis. A randomized controlled study. Ann Intern Med 114 (1991) 869-873
35. Ritzel U., Leonhardt U., Nather M., et al. Simvastatin in primary biliary cirrhosis: effects on serum lipids and distinct disease markers. J Hepatol 36 (2002) 454-458
36. Chalasani N. Statins and hepatotoxicity: focus on patients with fatty liver. Hepatology 41 (2005) 690-695
37. Vuppalanchi R., Teal E., and Chalasani N. Patients with elevated baseline liver enzymes do not have higher frequency of hepatotoxicity from lovastatin than those with normal baseline liver enzymes. Am J Med Sci 329 (2005) 62-65
38. Khorashadi S., Hasson N.K., and Cheung R.C. Incidence of statin hepatotoxicity in patients with hepatitis C. Clin Gastroenterol Hepatol 4 (2006) 902-907
39. Stojakovic T., Putz-Bankuti C., Fauler G., et al. Atorvastatin in patients with primary biliary cirrhosis and incomplete biochemical response to ursodeoxycholic acid. Hepatology 46 (2007) 776-784
40. Browning J.D. Statins and hepatic steatosis: perspectives from the Dallas Heart Study. Hepatology 44 (2006) 466-471
41. Lewis J.H., Mortensen M.E., Zweig S., et al. Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Hepatology 46 (2007) 1453-1463
42. O'Leary J.G., Chan J.L., McMahon C.M., et al. Atorvastatin does not exhibit antiviral activity against HCV at conventional doses: a pilot clinical trial. Hepatology 45 (2007) 895-898
43. Argo C.K., Loria P., Caldwell S.H., et al. Statins in liver disease: a molehill, an iceberg, or neither?. Hepatology 48 (2008) 662-669