Skip to main content
Log in

The Use of Statins in Patients With Chronic Liver Disease and Cirrhosis

  • Liver (J Bajaj, Section Editor)
  • Published:
Current Treatment Options in Gastroenterology Aims and scope Submit manuscript

Abstract

Purpose of review

Statins are drugs developed to treat hypercholesterolemia. Its use in patients with liver disease has been limited because one of its potential and most feared side effects is hepatotoxicity. However, there is robust evidence that supports the safety of statins in this population in the absence of severe liver dysfunction. In this review, we will summarize the efficacy and safety of statins in cirrhosis.

Recent findings

Statins are effective in the treatment of dyslipidemia in patients with liver disease, because of their pleiotropic properties. These properties are independent of their effect on cholesterol levels, such as improving endothelial dysfunction or having antioxidant, antifibrotic, anti-inflammatory, antiproliferative, antiangiogenic, proapoptotic, or immunomodulation properties. Statins have been studied in other areas such as in treatment of portal hypertension, prevention of hepatocellular carcinoma, and/or protection against ischemia/reperfusion injury.

Summary

Approved indications for statins in patients with cirrhosis are those of the general population, including dyslipidemia and increased cardiovascular risk. Compensated cirrhosis is not a contraindication. In patients with decompensated cirrhosis, statins should be prescribed with extreme caution at low doses, and with frequent monitoring of creatinine phosphokinase levels in order to detect adverse events in a timely fashion.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References and Recommended Reading

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

  1. Cabrera L, Abraldes J. Statins: The panacea of cirrhosis? Curr Hepatol Rep. 2016;15:1–7.

    Article  Google Scholar 

  2. 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 

  3. 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  CAS  PubMed  Google Scholar 

  4. Bosch J, Abraldes JG, Fernandez M, Garcia-Pagan JC. Hepatic endothelial dysfunction and abnormal angiogenesis: new targets in the treatment of portal hypertension. J Hepatol. 2010;53(3):558–67.

    Article  CAS  PubMed  Google Scholar 

  5. 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 

  6. •• 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(5):1160–70 e3. Prospective study that showed a lower mortality in patients that received statins.

    Article  CAS  PubMed  Google Scholar 

  7. 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 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. 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. Dig Liver Dis. 2015;47(11):957–63.

    Article  CAS  PubMed  Google Scholar 

  10. Wani ZA, Mohapatra S, Khan AA, Mohapatra A, Yatoo GN. Addition of simvastatin to carvedilol non responders: a new pharmacological therapy for treatment of portal hypertension. World J Hepatol. 2017;9(5):270–7.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Del Puppo M, Galli Kienle M, Crosignani A, Petroni ML, Amati B, Zuin M, et al. Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration. J Lipid Res. 2001;42(3):437–41.

    PubMed  Google Scholar 

  12. Kurihara T, Akimoto M, Abe K, Ishiguro H, Niimi A, Maeda A, et al. Experimental use of pravastatin in patients with primary biliary cirrhosis associated with hypercholesterolemia. Clin Ther. 1993;15(5):890–8.

    CAS  PubMed  Google Scholar 

  13. Ritzel U, Leonhardt U, Nather M, Schafer G, Armstrong VW, Ramadori G. Simvastatin in primary biliary cirrhosis: effects on serum lipids and distinct disease markers. J Hepatol. 2002;36(4):454–8.

    Article  CAS  PubMed  Google Scholar 

  14. Stojakovic T, Claudel T, Putz-Bankuti C, Fauler G, Scharnagl H, Wagner M, et al. Low-dose atorvastatin improves dyslipidemia and vascular function in patients with primary biliary cirrhosis after one year of treatment. Atherosclerosis. 2010;209(1):178–83.

    Article  CAS  PubMed  Google Scholar 

  15. 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 

  16. 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. https://doi.org/10.1002/14651858.CD008623.pub2.

    Google Scholar 

  17. •• Kargiotis K, Athyros VG, Giouleme O, Katsiki N, Katsiki E, Anagnostis P, et al. Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome. World J Gastroenterol. 2015;21(25):7860–8. This article shows that further investigation is needed regarding the role of statins in the treatment of NAFLD.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Simon TG, Bonilla H, Yan P, Chung RT, Butt AA. Atorvastatin and fluvastatin are associated with dose-dependent reductions in cirrhosis and hepatocellular carcinoma, among patients with hepatitis C virus: results from ERCHIVES. Hepatology. 2016;64(1):47–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. •• 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(2):430–40 e1. One of the largest observational studies showing a benefit of statins in patients with cirrhosis.

    Article  CAS  PubMed  Google Scholar 

  20. Harrison SA, Rossaro L, Hu KQ, Patel K, Tillmann H, Dhaliwal S, et al. Serum cholesterol and statin use predict virological response to peginterferon and ribavirin therapy. Hepatology. 2010;52(3):864–74.

    Article  CAS  PubMed  Google Scholar 

  21. Manzano-Robleda Mdel C, Ornelas-Arroyo V, Barrientos-Gutierrez T, Mendez-Sanchez N, Uribe M, Chavez-Tapia NC. Boceprevir and telaprevir for chronic genotype 1 hepatitis C virus infection. A systematic review and meta-analysis. Ann Hepatol. 2015;14(1):46–57.

    PubMed  Google Scholar 

  22. Chang FM, Wang YP, Lang HC, Tsai CF, Hou MC, Lee FY, et al. Statins decrease the risk of decompensation in hepatitis B virus- and hepatitis C virus-related cirrhosis: a population-based study. Hepatology. 2017;66:896–907.

    Article  CAS  PubMed  Google Scholar 

  23. Chen CI, Kuan CF, Fang YA, Liu SH, Liu JC, Wu LL, et al. Cancer risk in HBV patients with statin and metformin use: a population-based cohort study. Medicine (Baltimore). 2015;94(6):e462.

    Article  CAS  Google Scholar 

  24. Hsiang JC, Wong GL, Tse YK, Wong VW, Yip TC, Chan HL. Statin and the risk of hepatocellular carcinoma and death in a hospital-based hepatitis B-infected population: a propensity score landmark analysis. J Hepatol. 2015;63(5):1190–7.

    Article  CAS  PubMed  Google Scholar 

  25. Huang YW, Lee CL, Yang SS, Fu SC, Chen YY, Wang TC, 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(7):976–85.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  27. Lai SW, Liao KF, Lai HC, Muo CH, Sung FC, Chen PC. Statin use and risk of hepatocellular carcinoma. Eur J Epidemiol. 2013;28(6):485–92.

    Article  CAS  PubMed  Google Scholar 

  28. Singh S, Singh PP, Singh AG, Murad MH, Sanchez W. Statins are associated with a reduced risk of hepatocellular cancer: a systematic review and meta-analysis. Gastroenterology. 2013;144(2):323–32.

    Article  CAS  PubMed  Google Scholar 

  29. 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 

  30. Kumar S, Grace ND, Qamar AA. Statin use in patients with cirrhosis: a retrospective cohort study. Dig Dis Sci. 2014;59(8):1958–65.

    Article  CAS  PubMed  Google Scholar 

  31. 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.

    Article  CAS  PubMed  Google Scholar 

  32. •• Jose J. Statins and its hepatic effects: newer data, implications, and changing recommendations. J Pharm Bioallied Sci. 2016;8(1):23–8. Complete review mainly focused on the safety of statins from the liver perspective

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Black DM, Bakker-Arkema RG, Nawrocki JW. An overview of the clinical safety profile of atorvastatin (lipitor), a new HMG-CoA reductase inhibitor. Arch Intern Med. 1998;158(6):577–84.

    Article  CAS  PubMed  Google Scholar 

  34. Russo MW, Hoofnagle JH, Gu J, Fontana RJ, Barnhart H, Kleiner DE, et al. Spectrum of statin hepatotoxicity: experience of the drug-induced liver injury network. Hepatology. 2014;60(2):679–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Reuben A, Koch DG, Lee WM. Acute Liver Failure Study G. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52(6):2065–76. https://doi.org/10.1002/hep.23937.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Bjornsson ES. Hepatotoxicity of statins and other lipid-lowering agents. Liver Int. 2017;37(2):173–8.

    Article  PubMed  Google Scholar 

  37. Alla V, Abraham J, Siddiqui J, Raina D, Wu GY, Chalasani NP, et al. Autoimmune hepatitis triggered by statins. J Clin Gastroenterol. 2006;40(8):757–61.

    Article  CAS  PubMed  Google Scholar 

  38. http://livertox.nih.gov/.Accessed September 23, 2017.

  39. Chalasani N, Aljadhey H, Kesterson J, Murray MD, Hall SD. Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroenterology. 2004;126(5):1287–92.

    Article  CAS  PubMed  Google Scholar 

  40. Lewis JH, Mortensen ME, Zweig S, Fusco MJ, Medoff JR, Belder R, 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. 2007;46(5):1453–63.

    Article  CAS  PubMed  Google Scholar 

  41. Onofrei MD, Butler KL, Fuke DC, Miller HB. Safety of statin therapy in patients with preexisting liver disease. Pharmacotherapy. 2008;28(4):522–9.

    Article  CAS  PubMed  Google Scholar 

  42. •• Bays H, Cohen DE, Chalasani N, Harrison SA, The National Lipid Association’s Statin Safety Task F. An assessment by the Statin Liver Safety Task Force: 2014 update. J Clin Lipidol. 2014;8(3 Suppl):S47–57. Specific recommendations of a panel of experts about the liver safety of statins; the strength of the recommendations and quality of evidence are given.

    Article  PubMed  Google Scholar 

  43. Calderon RM, Cubeddu LX, Goldberg RB, Schiff ER. Statins in the treatment of dyslipidemia in the presence of elevated liver aminotransferase levels: a therapeutic dilemma. Mayo Clin Proc. 2010;85(4):349–56.

    Article  PubMed  PubMed Central  Google Scholar 

  44. 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 

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

    Article  PubMed  Google Scholar 

  46. 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 

  47. Targher G, Bertolini L, Padovani R, Rodella S, Arcaro G, Day C. Differences and similarities in early atherosclerosis between patients with non-alcoholic steatohepatitis and chronic hepatitis B and C. J Hepatol. 2007;46(6):1126–32.

    Article  CAS  PubMed  Google Scholar 

  48. Berzigotti A, Erice E, Gilabert R, Reverter E, Abraldes JG, Garcia-Pagan JC, et al. Cardiovascular risk factors and systemic endothelial function in patients with cirrhosis. Am J Gastroenterol. 2013;108(1):75–82.

    Article  CAS  PubMed  Google Scholar 

  49. Longo M, Crosignani A, Battezzati PM, Squarcia Giussani C, Invernizzi P, Zuin M, et al. Hyperlipidaemic state and cardiovascular risk in primary biliary cirrhosis. Gut. 2002;51(2):265–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sorokin A, Brown JL, Thompson PD. Primary biliary cirrhosis, hyperlipidemia, and atherosclerotic risk: a systematic review. Atherosclerosis. 2007;194(2):293–9.

    Article  CAS  PubMed  Google Scholar 

  51. Gaggini M, Morelli M, Buzzigoli E, DeFronzo RA, Bugianesi E, Gastaldelli A. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients. 2013;5(5):1544–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Syed GH, Amako Y, Siddiqui A. Hepatitis C virus hijacks host lipid metabolism. Trends Endocrinol Metab. 2010;21(1):33–40.

    Article  CAS  PubMed  Google Scholar 

  53. Bosch J, Forns X. Therapy Statins and liver disease: from concern to ‘wonder’ drugs? Nat Rev Gastroenterol Hepatol. 2015;12(6):320–1.

    Article  CAS  PubMed  Google Scholar 

  54. Ikeda M, Abe K, Yamada M, Dansako H, Naka K, Kato N. Different anti-HCV profiles of statins and their potential for combination therapy with interferon. Hepatology. 2006;44(1):117–25.

    Article  CAS  PubMed  Google Scholar 

  55. Sheridan DA, Bridge SH, Crossey MM, Felmlee DJ, Fenwick FI, Thomas HC, et al. Omega-3 fatty acids and/or fluvastatin in hepatitis C prior non-responders to combination antiviral therapy—a pilot randomised clinical trial. Liver Int. 2014;34(5):737–47.

    Article  CAS  PubMed  Google Scholar 

  56. 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  CAS  PubMed  Google Scholar 

  57. Bader T, Korba B. Simvastatin potentiates the anti-hepatitis B virus activity of FDA-approved nucleoside analogue inhibitors in vitro. Antivir Res. 2010;86(3):241–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Tsan YT, Lee CH, Wang JD, Chen PC. Statins and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection. J Clin Oncol. 2012;30(6):623–30.

    Article  PubMed  Google Scholar 

  59. •• 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;15:1521–30. Meta-analysis that reinforces the concept that statins may probably decrease mortality in patients with cirrhosis.

    Article  CAS  PubMed  Google Scholar 

  60. Istvan ES, Deisenhofer J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science. 2001;292(5519):1160–4.

    Article  CAS  PubMed  Google Scholar 

  61. 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 

  62. 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 

  63. Chang CC, Wang SS, Hsieh HG, Lee WS, Chuang CL, Lin HC, et al. Rosuvastatin improves hepatopulmonary syndrome through inhibition of inflammatory angiogenesis of lung. Clin Sci (Lond). 2015;129(6):449–60.

    Article  CAS  Google Scholar 

  64. 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 

  65. Meireles CZ, Pasarin M, Lozano JJ, Garcia-Caldero H, Gracia-Sancho J, Garcia-Pagan JC, et al. Simvastatin attenuates liver injury in rodents with biliary cirrhosis submitted to hemorrhage/resuscitation. Shock. 2017;47(3):370–7.

    Article  CAS  PubMed  Google Scholar 

  66. Trebicka J, Hennenberg M, Odenthal M, Shir K, Klein S, Granzow M, et al. Atorvastatin attenuates hepatic fibrosis in rats after bile duct ligation via decreased turnover of hepatic stellate cells. J Hepatol. 2010;53(4):702–12.

    Article  CAS  PubMed  Google Scholar 

  67. Abraldes JG, Burak KW. STAT order: should patients with chronic liver disease be prescribed statins to prevent fibrosis progression and hepatocellular carcinoma? Hepatology. 2016;64(1):13–5.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Aldo J. Montano-Loza MD, PhD.

Ethics declarations

Conflict of Interest

Carlos Moctezuma-Velázquez declares that he has no conflict of interest. Juan Abraldes declares that he has no conflict of interest. Aldo Montano-Loza declares that he has no conflict of interest.

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

Juan G. Abraldes and Aldo J. Montano-Loza are co-senior authors

This article is part of the Topical Collection on Liver

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moctezuma-Velázquez, C., Abraldes, J.G. & Montano-Loza, A.J. The Use of Statins in Patients With Chronic Liver Disease and Cirrhosis. Curr Treat Options Gastro 16, 226–240 (2018). https://doi.org/10.1007/s11938-018-0180-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11938-018-0180-4

Keywords

Navigation