Skip to main content
SpringerLink
Log in

Statins: the Panacea of Cirrhosis?

  • Management of the Cirrhotic Patient (A Cardenas and N Reau, Section Editors)
  • Published:
Current Hepatology Reports Aims and scope Submit manuscript

Abstract

Cirrhosis and portal hypertension are associated with intrahepatic endothelial dysfunction, which creates a proinflammatory and profibrotic environment and increases hepatic resistance and portal pressure. Statins have shown to improve the liver endothelial dysfunction and decrease the portal pressure in preclinical models of cirrhosis. In humans, they have shown anti-inflmatory and antifibrotic effects in the liver. This suggests that statins can target several pathogenic events in cirrhosis and have potential to improve the prognosis in these patients. This needs further evaluation in adequately designed randomized trials with clinical endpoints.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Tobert JA. Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors. Nat Rev Drug Discov. 2003;2(7):517–26.

    Article  CAS  PubMed  Google Scholar 

  2. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344(8934):1383–9.

  3. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, Macfarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333(20):1301–7.

    Article  CAS  PubMed  Google Scholar 

  4. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. Jama. 1998;279(20):1615–22.

    Article  CAS  PubMed  Google Scholar 

  5. Sacks FM, Moye LA, Davis BR, Cole TG, Rouleau JL, Nash DT, et al. Relationship between plasma LDL concentrations during treatment with pravastatin and recurrent coronary events in the Cholesterol and Recurrent Events trial. Circulation. 1998;97(15):1446–52.

    Article  CAS  PubMed  Google Scholar 

  6. Qiuping G, Ryne P-R. Prescription cholesterol-lowering medication use in adults aged 40 and over: United States, 2003–2012 2014 [cited 2015 02/09/2015]. Available from: http://www.cdc.gov/nchs/data/databriefs/db177.pdf.

  7. Ioannidis JP. More than a billion people taking statins?: Potential implications of the new cardiovascular guidelines. Jama. 2014;311(5):463–4.

    Article  CAS  PubMed  Google Scholar 

  8. Sirtori CR. The pharmacology of statins. Pharmacol Res. 2014;88:3–11.

    Article  CAS  PubMed  Google Scholar 

  9. Mihos CG, Santana O. Pleiotropic effects of the HMG-CoA reductase inhibitors. Int J General Med. 2011;4:261–71.

    CAS  Google Scholar 

  10. Cortes-Bergoderi M, Pineda AM, Santana O. The pleiotropic effects and therapeutic potential of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in gastrointestinal tract disorders: a comprehensive review. J Gastrointest Liver Dis JGLD. 2013;22(2):199–204.

    Google Scholar 

  11. Bonetti PO, Lerman LO, Napoli C, Lerman A. Statin effects beyond lipid lowering—are they clinically relevant? Eur Heart J. 2003;24(3):225–48.

    Article  CAS  PubMed  Google Scholar 

  12. Dangas G, Smith DA, Unger AH, Shao JH, Meraj P, Fier C, et al. Pravastatin: an antithrombotic effect independent of the cholesterol-lowering effect. Thromb Haemost. 2000;83(5):688–92.

    CAS  PubMed  Google Scholar 

  13. Lefer DJ. Statins as potent antiinflammatory drugs. Circulation. 2002;106(16):2041–2.

    Article  PubMed  Google Scholar 

  14. Bates K, Ruggeroli CE, Goldman S, Gaballa MA. Simvastatin restores endothelial NO-mediated vasorelaxation in large arteries after myocardial infarction. Am J Physiol Heart Circ Physiol. 2002;283(2):H768–75.

    Article  CAS  PubMed  Google Scholar 

  15. Laufs U, Gertz K, Dirnagl U, Bohm M, Nickenig G, Endres M. Rosuvastatin, a new HMG-CoA reductase inhibitor, upregulates endothelial nitric oxide synthase and protects from ischemic stroke in mice. Brain Res. 2002;942(1–2):23–30.

    Article  CAS  PubMed  Google Scholar 

  16. Davignon J, Jacob RF, Mason RP. The antioxidant effects of statins. Coron Artery Dis. 2004;15(5):251–8.

    Article  PubMed  Google Scholar 

  17. Stoll LL, McCormick ML, Denning GM, Weintraub NL. Antioxidant effects of statins. Drugs Today. 2004;40(12):975–90.

    Article  CAS  PubMed  Google Scholar 

  18. Goppelt-Struebe M, Hahn A, Iwanciw D, Rehm M, Banas B. Regulation of connective tissue growth factor (ccn2; ctgf) gene expression in human mesangial cells: modulation by HMG CoA reductase inhibitors (statins). Mol Pathol. 2001;54(3):176–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Eberlein M, Heusinger-Ribeiro J, Goppelt-Struebe M. Rho-dependent inhibition of the induction of connective tissue growth factor (CTGF) by HMG CoA reductase inhibitors (statins). Br J Pharmacol. 2001;133(7):1172–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Shyu KG, Wang BW, Chen WJ, Kuan P, Hung CR. Mechanism of the inhibitory effect of atorvastatin on endoglin expression induced by transforming growth factor-beta1 in cultured cardiac fibroblasts. Eur J Heart Fail. 2010;12(3):219–26.

    Article  CAS  PubMed  Google Scholar 

  21. Steffens S, Mach F. Anti-inflammatory properties of statins. Semin Vasc Med. 2004;4(4):417–22.

    Article  PubMed  Google Scholar 

  22. Bu DX, Griffin G, Lichtman AH. Mechanisms for the anti-inflammatory effects of statins. Curr Opin Lipidol. 2011;22(3):165–70.

    Article  CAS  PubMed  Google Scholar 

  23. Blanco-Colio LM, Tunon J, Martin-Ventura JL, Egido J. Anti-inflammatory and immunomodulatory effects of statins. Kidney Int. 2003;63(1):12–23.

    Article  CAS  PubMed  Google Scholar 

  24. Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, et al. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014;50(16):2822–30.

    Article  CAS  PubMed  Google Scholar 

  25. Hong JY, Nam EM, Lee J, Park JO, Lee SC, Song SY, et al. Randomized double-blinded, placebo-controlled phase II trial of simvastatin and gemcitabine in advanced pancreatic cancer patients. Cancer Chemother Pharmacol. 2014;73(1):125–30.

    Article  CAS  PubMed  Google Scholar 

  26. Han JY, Lee SH, Yoo NJ, Hyung LS, Moon YJ, Yun T, et al. A randomized phase II study of gefitinib plus simvastatin versus gefitinib alone in previously treated patients with advanced non-small cell lung cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2011;17(6):1553–60.

    Article  CAS  Google Scholar 

  27. Konings IR, van der Gaast A, van der Wijk LJ, de Jongh FE, Eskens FA, Sleijfer S. The addition of pravastatin to chemotherapy in advanced gastric carcinoma: a randomised phase II trial. Eur J Cancer. 2010;46(18):3200–4.

    Article  CAS  PubMed  Google Scholar 

  28. Linden KG, Leachman SA, Zager JS, Jakowatz JG, Viner JL, McLaren CE, et al. A randomized, double-blind, placebo-controlled phase II clinical trial of lovastatin for various endpoints of melanoma pathobiology. Cancer Prevent Res. 2014;7(5):496–504.

    Article  CAS  Google Scholar 

  29. National Heart L, Blood Institute ACTN, Truwit JD, Bernard GR, Steingrub J, Matthay MA, et al. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014;370(23):2191–200.

    Article  Google Scholar 

  30. Kruger P, Bailey M, Bellomo R, Cooper DJ, Harward M, Higgins A, et al. A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis. Am J Respir Crit Care Med. 2013;187(7):743–50.

    Article  CAS  PubMed  Google Scholar 

  31. Papazian L, Roch A, Charles PE, Penot-Ragon C, Perrin G, Roulier P, et al. Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial. Jama. 2013;310(16):1692–700.

    Article  CAS  PubMed  Google Scholar 

  32. Patel JM, Snaith C, Thickett DR, Linhartova L, Melody T, Hawkey P, et al. Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial). Crit Care. 2012;16(6):R231.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Kruger PS, Harward ML, Jones MA, Joyce CJ, Kostner KM, Roberts MS, et al. Continuation of statin therapy in patients with presumed infection: a randomized controlled trial. Am J Respir Crit Care Med. 2011;183(6):774–81.

    Article  CAS  PubMed  Google Scholar 

  34. John ME, Cockcroft JR, Mckeever TM, Coward WR, Shale DJ, Johnson SR, et al. Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a randomized controlled trial. Int J Chron Obstruct Pulm Dis. 2015;10:211–21.

    Article  Google Scholar 

  35. Criner GJ, Connett JE, Aaron SD, Albert RK, Bailey WC, Casaburi R, et al. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med. 2014;370(23):2201–10.

    Article  PubMed Central  PubMed  Google Scholar 

  36. McAuley DF, Laffey JG, O’Kane CM, Perkins GD, Mullan B, Trinder TJ, et al. Simvastatin in the acute respiratory distress syndrome. N Engl J Med. 2014;371(18):1695–703.

    Article  PubMed  Google Scholar 

  37. Kaczmarek P, Sladek K, Skucha W, Rzeszutko M, Iwaniec T, Dziedzina S, et al. The influence of simvastatin on selected inflammatory markers in patients with chronic obstructive pulmonary disease. Pol Arch Med Wewn. 2010;120(1–2):11–7.

    CAS  PubMed  Google Scholar 

  38. Lee TM, Chen CC, Shen HN, Chang NC. Effects of pravastatin on functional capacity in patients with chronic obstructive pulmonary disease and pulmonary hypertension. Clin Sci. 2009;116(6):497–505.

    Article  CAS  PubMed  Google Scholar 

  39. Sorensen PS, Lycke J, Eralinna JP, Edland A, Wu X, Frederiksen JL, et al. Simvastatin as add-on therapy to interferon beta-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial. Lancet Neurol. 2011;10(8):691–701.

    Article  CAS  PubMed  Google Scholar 

  40. Kamm CP, El-Koussy M, Humpert S, Findling O, von Bredow F, Burren Y, et al. Atorvastatin added to interferon beta for relapsing multiple sclerosis: a randomized controlled trial. J Neurol. 2012;259(11):2401–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Sano M, Bell KL, Galasko D, Galvin JE, Thomas RG, van Dyck CH, et al. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology. 2011;77(6):556–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Feldman HH, Doody RS, Kivipelto M, Sparks DL, Waters DD, Jones RW, et al. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology. 2010;74(12):956–64.

    Article  CAS  PubMed  Google Scholar 

  43. Fatemi A, Moosavi M, Sayedbonakdar Z, Farajzadegan Z, Kazemi M, Smiley A. Atorvastatin effect on systemic lupus erythematosus disease activity: a double-blind randomized clinical trial. Clin Rheumatol. 2014;33(9):1273–8.

    Article  PubMed  Google Scholar 

  44. Dhamija P, Hota D, Kochhar R, Sachdev A, Chakrabarti A. Randomized clinical trial: atorvastatin versus placebo in patients with acute exacerbation of mild to moderate ulcerative colitis. Indian J Gastroenterol Off J Indian Soc Gastroenterol. 2014;33(2):151–6.

    Article  Google Scholar 

  45. van der Vaart T, Plasschaert E, Rietman AB, Renard M, Oostenbrink R, Vogels A, et al. Simvastatin for cognitive deficits and behavioural problems in patients with neurofibromatosis type 1 (NF1-SIMCODA): a randomised, placebo-controlled trial. Lancet Neurol. 2013;12(11):1076–83.

    Article  PubMed  Google Scholar 

  46. Stojakovic T, Putz-Bankuti C, Fauler G, Scharnagl H, Wagner M, Stadlbauer V, et al. Atorvastatin in patients with primary biliary cirrhosis and incomplete biochemical response to ursodeoxycholic acid. Hepatology. 2007;46(3):776–84.

    Article  CAS  PubMed  Google Scholar 

  47. Stanca CM, Bach N, Allina J, Bodian C, Bodenheimer Jr H, Odin JA. Atorvastatin does not improve liver biochemistries or Mayo Risk Score in primary biliary cirrhosis. Dig Dis Sci. 2008;53(7):1988–93.

    Article  CAS  PubMed  Google Scholar 

  48. Cash WJ, O’Neill S, O’Donnell ME, McCance DR, Young IS, Mceneny J, et al. Randomized controlled trial assessing the effect of simvastatin in primary biliary cirrhosis. Liver Int Off J Int Assoc Stud Liver. 2013;33(8):1166–74.

    CAS  Google Scholar 

  49. Eslami L, Merat S, Malekzadeh R, Nasseri-Moghaddam S, Aramin H. Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Cochrane Database Syst Rev. 2013;12:CD008623.

    PubMed  Google Scholar 

  50. Dongiovanni P, Petta S, Mannisto V, Mancina RM, Pipitone R, Karja V, et al. Statin use and non-alcoholic steatohepatitis in at risk individuals. J Hepatol. 2015;63(3):705–12.

    Article  CAS  PubMed  Google Scholar 

  51. Pandya P, Rzouq F, Oni O. Sustained virologic response and other potential genotype-specific roles of statins among patients with hepatitis C-related chronic liver diseases. Clin Res Hepatol Gastroenterol. 2015;39(5):555–65.

    Article  CAS  PubMed  Google Scholar 

  52. Butt AA, Yan P, Bonilla H, Abou-Samra AB, Shaikh OS, Simon TG, et al. Effect of addition of statins to antiviral therapy in HCV infected persons: results from ERCHIVES. Hepatology. 2015;62(2):365–74.

    Article  CAS  PubMed  Google Scholar 

  53. Simon TG, King LY, Zheng H, Chung RT. Statin use is associated with a reduced risk of fibrosis progression in chronic hepatitis C. J Hepatol. 2015;62(1):18–23.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Selic Kurincic T, Lesnicar G, Poljak M, Meglic Volkar J, Rajter M, Prah J, et al. Impact of added fluvastatin to standard-of-care treatment on sustained virological response in naive chronic hepatitis C Patients infected with genotypes 1 and 3. Intervirology. 2014;57(1):23–30.

    Article  CAS  PubMed  Google Scholar 

  55. Tsan YT, Lee CH, Ho WC, Lin MH, Wang JD, Chen PC. Statins and the risk of hepatocellular carcinoma in patients with hepatitis C virus infection. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(12):1514–21.

    Article  Google Scholar 

  56. Rao GA, Pandya PK. Statin therapy improves sustained virologic response among diabetic patients with chronic hepatitis C. Gastroenterology. 2011;140(1):144–52.

    Article  CAS  PubMed  Google Scholar 

  57. Bader T, Hughes LD, Fazili J, Frost B, Dunnam M, Gonterman A, et al. A randomized controlled trial adding fluvastatin to peginterferon and ribavirin for naive genotype 1 hepatitis C patients. J Viral Hepat. 2013;20(9):622–7.

    Article  CAS  PubMed  Google Scholar 

  58. Kondo C, Atsukawa M, Tsubota A, Itokawa N, Fukuda T, Matsushita Y, et al. An open-label randomized controlled study of pegylated interferon/ribavirin combination therapy for chronic hepatitis C with versus without fluvastatin. J Viral Hepat. 2012;19(9):615–22.

    Article  CAS  PubMed  Google Scholar 

  59. Milazzo L, Caramma I, Mazzali C, Cesari M, Olivetti M, Galli M, et al. Fluvastatin as an adjuvant to pegylated interferon and ribavirin in HIV/hepatitis C virus genotype 1 co-infected patients: an open-label randomized controlled study. J Antimicrob Chemother. 2010;65(4):735–40.

    Article  CAS  PubMed  Google Scholar 

  60. Zhu Q, Li N, Han Q, Zhang P, Yang C, Zeng X, et al. Statin therapy improves response to interferon alfa and ribavirin in chronic hepatitis C: a systematic review and meta-analysis. Antivir Res. 2013;98(3):373–9.

    Article  CAS  PubMed  Google Scholar 

  61. Zafra C, Abraldes JG, Turnes J, Berzigotti A, Fernandez M, Garca-Pagan JC, et al. Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis. Gastroenterology. 2004;126(3):749–55.

    Article  CAS  PubMed  Google Scholar 

  62. Sikuler E, Groszmann RJ. Interaction of flow and resistance in maintenance of portal hypertension in a rat model. Am J Physiol. 1986;250(2 Pt 1):G205–12.

    CAS  PubMed  Google Scholar 

  63. Groszmann RJ, Abraldes JG. Portal hypertension: from bedside to bench. J Clin Gastroenterol. 2005;39(4 Suppl 2):S125–30.

    Article  PubMed  Google Scholar 

  64. Bathal PS, Grossmann HJ. Reduction of the increased portal vascular resistance of the isolated perfused cirrhotic rat liver by vasodilators. J Hepatol. 1985;1:325–9.

    Article  Google Scholar 

  65. Bosch J, Abraldes JG, Groszmann R. Current management of portal hypertension. J Hepatol. 2003;38 Suppl 1:S54–68.

    Article  PubMed  Google Scholar 

  66. Xie G, Wang X, Wang L, Wang L, Atkinson RD, Kanel GC, et al. Role of differentiation of liver sinusoidal endothelial cells in progression and regression of hepatic fibrosis in rats. Gastroenterology. 2012;142(4):918–27.

    Article  PubMed Central  PubMed  Google Scholar 

  67. Deleve LD, Wang X, Guo Y. Sinusoidal endothelial cells prevent rat stellate cell activation and promote reversion to quiescence. Hepatology. 2008;48(3):920–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Kureishi Y, Luo Z, Shiojima I, Bialik A, Fulton D, Lefer DJ, et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med. 2000;6(9):1004–10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Abraldes JG, Rodriguez-Vilarrupla A, Graupera M, Zafra C, Garcia-Caldero H, Garcia-Pagan JC, et al. Simvastatin treatment improves liver sinusoidal endothelial dysfunction in CCl4 cirrhotic rats. J Hepatol. 2007;46(6):1040–6.

    Article  CAS  PubMed  Google Scholar 

  70. La Mura V, Pasarin M, Meireles CZ, Miquel R, Rodriguez-Vilarrupla A, Hide D, et al. Effects of simvastatin administration on rodents with lipopolysaccharide-induced liver microvascular dysfunction. Hepatology. 2013;57(3):1172–81.

    Article  PubMed  Google Scholar 

  71. Trebicka J, Hennenberg M, Laleman W, Shelest N, Biecker E, Schepke M, 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(1):242–53.

    Article  CAS  PubMed  Google Scholar 

  72. Marrone G, Maeso-Diaz R, Garcia-Cardena G, Abraldes JG, Garcia-Pagan JC, Bosch J, et al. KLF2 exerts antifibrotic and vasoprotective effects in cirrhotic rat livers: behind the molecular mechanisms of statins. Gut. 2015;64(9):1434–43.

    Article  PubMed  Google Scholar 

  73. Uschner FE, Ranabhat G, Choi SS, Granzow M, Klein S, Schierwagen R, et al. Statins activate the canonical hedgehog-signaling and aggravate non-cirrhotic portal hypertension, but inhibit the non-canonical hedgehog signaling and cirrhotic portal hypertension. Sci Rep. 2015;5:14573.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Moreno M, Ramalho LN, Sancho-Bru P, Ruiz-Ortega M, Ramalho F, Abraldes JG, et al. Atorvastatin attenuates angiotensin II-induced inflammatory actions in the liver. Am J Physiol Gastrointest Liver Physiol. 2009;296(2):G147–56.

    Article  CAS  PubMed  Google Scholar 

  75. Meireles CZ, Pasarin M, Lozano JJ, Garcia-Caldero H, Gracia-Sancho J, Garcia Pagan JC, et al. Simvastatin prevents liver microvascular dysfunction and attenuates liver injury in rats with biliary cirrhosis submitted to hemorrhage/resuscitation. Hepatology. 2013;58(4 (Suppl)).

  76. Russo L, Gracia-Sancho J, Garcia-Caldero H, Marrone G, Garcia-Pagan JC, Garcia-Cardena G, et al. Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers. Hepatology. 2012;55(3):921–30.

    Article  CAS  PubMed  Google Scholar 

  77. Gracia-Sancho J, Garcia-Caldero H, Hide D, Marrone G, Guixe-Muntet S, Peralta C, et al. Simvastatin maintains function and viability of steatotic rat livers procured for transplantation. J Hepatol. 2013;58(6):1140–6.

    Article  CAS  PubMed  Google Scholar 

  78. Relja B, Lehnert M, Seyboth K, Bormann F, Hohn C, Czerny C, et al. Simvastatin reduces mortality and hepatic injury after hemorrhage/resuscitation in rats. Shock. 2010;34(1):46–54.

    Article  CAS  PubMed  Google Scholar 

  79. Drolz A, Horvatits T, Michl B, Roedl K, Schellongowski P, Holzinger U, et al. Statin therapy is associated with reduced incidence of hypoxic hepatitis in critically ill patients. J Hepatol. 2014;60(6):1187–93.

    Article  CAS  PubMed  Google Scholar 

  80. Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144(7):1426–37, 37 e1-9.

  81. Abraldes JG, Albillos A, Banares R, Turnes J, Gonzalez R, Garcia-Pagan JC, et al. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology. 2009;136(5):1651–8. Randomized controlled trial showing that treatment during 1 month with simvastatin significantly decreased HVPG without deleterious effects in systemic hemodynamics and improved quantitative tests of liver function in patients with cirrhosis.

    Article  CAS  PubMed  Google Scholar 

  82. Pollo-Flores P, Soldan M, Santos UC, Kunz DG, Mattos DE, da Silva AC, et al. Three months of simvastatin therapy vs. placebo for severe portal hypertension in cirrhosis: a randomized controlled trial. Digestive and liver disease: official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2015. A 3 month randomized controlled trial showing that simvastatin induces a clinically relevant decrease HVPG and improves liver function in patients with cirrhotic portal hypertension.

  83. Kumar S, Grace ND, Qamar AA. Statin use in patients with cirrhosis: a retrospective cohort study. Dig Dis Sci. 2014;59(8):1958–65. Retrospective cohort study showing that statin users had lower mortality on multivariate analysis, and Child–Pugh A patients had longer survival. Statin therapy may delay decompensation.

    Article  CAS  PubMed  Google Scholar 

  84. Motzkus-Feagans C, Pakyz AL, Ratliff SM, Bajaj JS, Lapane KL. Statin use and infections in veterans with cirrhosis. Aliment Pharmacol Ther. 2013;38(6):611–8. Retrospective cohort study showing that compensated cirrhotic patients using statins experienced less hospitalisations with infections than non-users.

    Article  CAS  PubMed  Google Scholar 

  85. Mohanty A, Tate J, Garcia-Tsao G. Statins are associated with a decreased. Risk of decompensation and death in veterans with hepatitis c-related compensated cirrhosis. Gastroenterology. 2015. doi:10.1053/j.gastro.2015.10.007. Retrospective cohort study showing that statin use in hepatitis C virus (HCV)-infected patients with compensated cirrhosis is associated with over 40% lower risk of hepatic decompensation and death.

    PubMed  Google Scholar 

  86. Abraldes JG, Villanueva C, Aracil C, Turnes J, Hernandez-Guerra M, Genesca J, et al. for the BLEPS Study Group. 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. doi:10.1053/j.gastro.2016.01.004. The only RCT of simvastatin in cirrhotics assesing clinical endpoints. This is a long-term (24 months) double-blind RCT showing a significant survival benefit in cirrhotic patients after variceal bleeding treated with simvastatin in add-on to standard therapy. Simvastatin was not superior to placebo in preventing the primary endpoint (a composite of rebleeding or death.

  87. Villanueva C, Albillos A, Genesca J, Abraldes JG, Calleja JL, Aracil C, et al. Development of hyperdynamic circulation and response to beta-blockers in compensated cirrhosis with portal hypertension. Hepatology. 2015;27(1):20–6.

    Google Scholar 

  88. Ripoll C, Groszmann R, Garcia-Tsao G, Grace N, Burroughs A, Planas R, et al. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology. 2007;133(2):481–8.

    Article  CAS  PubMed  Google Scholar 

  89. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S1–45.

    Article  PubMed  Google Scholar 

  90. de Lemos JA, Blazing MA, Wiviott SD, Lewis EF, Fox KA, White HD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. Jama. 2004;292(11):1307–16.

    Article  PubMed  Google Scholar 

  91. Study of the Effectiveness of Additional Reductions in C, Homocysteine Collaborative G, Armitage J, Bowman L, Wallendszus K, Bulbulia R, et al. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet. 2010;376(9753):1658–69.

    Article  Google Scholar 

  92. Group SC, Link E, Parish S, Armitage J, Bowman L, Heath S, et al. SLCO1B1 variants and statin-induced myopathy—a genomewide study. N Engl J Med. 2008;359(8):789–99.

    Article  Google Scholar 

  93. Hou Q, Li S, Li L, Li Y, Sun X, Tian H. Association between SLCO1B1 gene T521C polymorphism and statin-related myopathy risk: a meta-analysis of case–control studies. Medicine. 2015;94(37):e1268.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  94. Theile D, Haefeli WE, Seitz HK, Millonig G, Weiss J, Mueller S. Association of liver stiffness with hepatic expression of pharmacokinetically important genes in alcoholic liver disease. Alcohol Clin Exp Res. 2013;37 Suppl 1:E17–22.

    Article  CAS  PubMed  Google Scholar 

  95. More VR, Cheng Q, Donepudi AC, Buckley DB, Lu ZJ, Cherrington NJ, et al. Alcohol cirrhosis alters nuclear receptor and drug transporter expression in human liver. Drug Metab Dispos Biol Fate Chem. 2013;41(5):1148–55.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  96. Santos PC, Gagliardi AC, Miname MH, Chacra AP, Santos RD, Krieger JE, et al. SLCO1B1 haplotypes are not associated with atorvastatin-induced myalgia in Brazilian patients with familial hypercholesterolemia. Eur J Clin Pharmacol. 2012;68(3):273–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cirrhosis Care Clinic (CCC), Liver Unit, Division of Gastroenterology, University of Alberta, 1-34 Zeidler Ledcor Building, Edmonton, AB, T6G-2X8, Canada

    Lourdes Cabrera & Juan G. Abraldes

Authors
  1. Lourdes Cabrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juan G. Abraldes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juan G. Abraldes.

Ethics declarations

Conflicts of Interest

Lourdes Cabrera declares that she has no conflicts of interest. Juan G. Abraldes reports personal fees from Janssen, personal fees from Promethera Biosciences, and personal fees from Gore, outside the submitted work.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Management of the Cirrhotic Patient

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cabrera, L., Abraldes, J.G. Statins: the Panacea of Cirrhosis?. Curr Hepatology Rep 15, 1–7 (2016). https://doi.org/10.1007/s11901-016-0287-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11901-016-0287-9

Keywords

Search

Navigation