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Category: Volume 07 Issue 04 April 2019
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Title: Evaluating the Role of Statins in Patients with non-Alcoholic Fatty Liver Disease (NAFLD)

Authors: Dr Gagan Gunjan, Dr P.K.Agrawal, Dr Krishna Baruah

 DOI: https://dx.doi.org/10.18535/jmscr/v7i4.164

Abstract

Introduction

Non-alcoholic fatty liver disease is an emerging liver disease in Indian and Western countries. It is defined as fatty infiltration of liver with a spectrum of disorders ranging from simple fatty liver to non alcoholic staeatohepatitis to fibrosis/cirrhosis attributable to various risk factors like Obesity, hyperlipidaemia, Type2 DM and insulin resistance.1,2 Fatty liver is not an unusual finding nowadays-being recognized in 30-40% of general population, 10-20% of normal weight individuals and 70-80% of obese individuals.4,5

It is one of the most frequent causes of incidental elevation of serum liver enzymes. Dyslipidaemia is frequently observed in patients with non-alcoholic fatty liver disease and treatment with statins play a critical role in overall management of these patients. NAFLD is now recognized as the most prevalent chronic liver disease, a situation that is not going to change soon and statins play a crucial role in lowering the risk of cardiovascular events shown in several clinical trials. Global prevalence of NAFLD is estimated to be between 25% and 33%.9,10

Objective

The primary objective is to demonstrate beneficial role of statins in patients of NAFLD with minimal effect on liver transaminases (ALT/AST) thus making it a promising drug for the same.

References

  1. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55:2005–2023. doi:10.1002/hep.25762. [PubMed] [CrossRef] [Google Scholar]
  2. Angulo P. Diagnosing steatohepatitis and predicting liver-related mortality in patients with NAFLD: two distinct concepts. Hepatology. 2011;53:1792–1794. doi:10.1002/hep.24403. [PubMed] [CrossRef] [Google Scholar]
  3. Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002;123:745-50.
  4. Loomba, A.J. SanyalThe global NAFLD epidemic Nature Reviews Gastroenterology &Hepatology, 10 (2013), pp. 686-690Google Scholar
  5. Pais, F. Charlotte, L. Fedchuk, et al.A systematic review of follow-up biopsies reveals disease progression in patients with non-alcoholic fatty liverJournal of Hepatology, 59 (2013), pp. 550-556 Google Scholar
  6. Vernon, A. Baranova, Z.M. Younossi Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults Alimentary Pharmacology and Therapeutics, 34 (2011), pp. 274-285Google Scholar
  7. R. Souza, F. Diniz Mde, J.E. Medeiros-Filho, et al.Metabolic syndrome and risk factors for non-alcoholic fatty liver disease Arquivos de Gastroenterologia, 49 (2012), pp. 89-96Google Scholar
  8. Ballestri, A. Lonardo, S. Bonapace, et al.Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease World Journal of Gastroenterology, 20 (2014), pp. 1724-1745Google Scholar
  9. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease—meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2015;64:73–84. doi:101002/hep.28431. [PubMed] [Google Scholar]
  10. Lazo M, Clark JM. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis. 2008;28:339–350. doi:10.1055/s-0028-1091978. [PubMed] [CrossRef] [Google Scholar]
  11. Labrecque DR, Abbas Z, Anania F, et al. World Gastroenterology Organisation global guidelines: nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J Clin Gastroenterol. 2014;48:467–473. doi:10.1097/MCG.0000000000000116. [PubMed] [CrossRef] [Google Scholar]
  12. Pignatelli, R. Carnevale, D. Pastori, et al.Immediate antioxidant and antiplatelet effect of atorvastatin via inhibition of Nox2 Circulation, 126 (2012), pp. 92-103Google Scholar
  13. Violi, C. Calvieri, D. Ferro, et al.Statins as antithrombotic drugs Circulation, 127 (2013), pp. 251-257Google Scholar
  14. Del Ben, L. Polimeni, R. Carnevale, et al.NOX2-generated oxidative stress is associated with severity of ultrasound liver steatosis in patients with non-alcoholic fatty liver disease BMC Gastroenterology, 14 (2014), p. 81
  15. G. Athyros, K. Tziomalos, T.D. Gossios, et al.Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis Lancet, 376 (2010), pp. 1916-1922
  16. A. DujovneSide effects of statins: hepatitis versus “transaminitis”-myositis versus “CPK it is” American Journal of Cardiology, 89 (2002), pp. 1411-1413Google Scholar
  17. Screening experience and baseline characteristics in the West of Scotland Coronary Prevention Study. The WOSCOPS Study Group. West of Scotland Coronary Prevention Study American Journal of Cardiology, 76 (1995), pp. 485-491Google Scholar
  18. M. Sacks, M.A. Pfeffer, L. Moye, et al.Rationale and design of a secondary prevention trial of lowering normal plasma cholesterol levels after acute myocardial infarction: the Cholesterol and Recurrent Events trial (CARE) American Journal of Cardiology, 68 (1991), pp. 1436-1446Google Scholar
  19. Design features and baseline characteristics of the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) Study: a randomized trial in patients with previous acute myocardial infarction and/or unstable angina pectoris American Journal of Cardiology, 76 (1995), pp. 474-479
  20. de Denus, S.A. Spinler, K. Miller, et al.Statins and liver toxicity: a meta-analysis Pharmacotherapy, 24 (2004), pp. 584-591
  21. A. Alsheikh-Ali, P.V. Maddukuri, H. Han, et al. Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer: insights from large randomized statin trials Journal of the American College of Cardiology, 50 (2007), pp. 409-418Google Scholar
  22. M. Dale, C.M. White, N.N. Henyan, et al. Impact of statin dosing intensity on transaminase and creatine kinase American Journal of Medicine, 120 (2007), pp. 706-712
  23. Tzefos M, Olin JL. 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitor use in chronic liver disease: a therapeutic controversy. J Clin Lipidol. 2011;5:450–459. doi:10.1016/j.jacl.2011.06.013. [PubMed] [CrossRef] [Google Scholar]
  24. de Keyser CE, Koehler EM, Schouten JN, et al. Statin therapy is associated with a reduced risk of non-alcoholic fatty liver in overweight individuals. Dig Liver Dis. 2014;46:720–725. doi:10.1016/j.dld.2014.04.002. [PubMed] [CrossRef] [Google Scholar]
  25. Maroni L, Guasti L, Castiglioni L, et al. Lipid targets during statin treatment in dyslipidemia patients affected by nonalcoholic fatty liver disease. Am J Med Sci. 2011;342:383–387. doi:10.1097/MAJ.0b013e318213e526. [PubMed] [CrossRef] [Google Scholar]
  26. Rana H, Yadav SS, Reddy HD, Singhal S, Singh DK, Usman K. Comparative effect of insulin sensitizers and statin on metabolic profile and ultrasonographical score in non alcoholic fatty liver disease. J Clin Diagn Res. 2016;10:OC19–OC23.
  27. C. LaRosa, S.M. Grundy, D.D. Waters, et al.Intensive lipid lowering with atorvastatin in patients with stable coronary disease New England Journal of Medicine, 352 (2005), pp. 1425-1435Google Scholar
  28. A. Blazing, J.A. De Lemos, C.K. Dyke, et al. The A-to-Z Trial: methods and rationale for a single trial investigating combined use of low-molecular-weight heparin with the glycoprotein IIb/IIIa inhibitor tirofiban and defining the efficacy of early aggressive simvastatin therapy American Heart Journal, 142 (2001), pp. 211-217
  29. Eslami, S. Merat, R. Malekzadeh, et al.Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis Cochrane Database of Systematic Reviews, 12 (2013), p. CD008623Google Scholar
  30. G. Athyros, D.P. Mikhailidis, T.P. Didangelos, et al. Effect of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome: a randomised studyCurrent Medical Research and Opinion, 22 (2006), pp. 873-883Google Scholar
  31. E. de Keyser, E.M. Koehler, J.N. Schouten, et al. Statin therapy is associated with a reduced risk of non-alcoholic fatty liver in overweight individuals Digestive and Liver Disease, 46 (2014), pp. 720-725Google Scholar
  32. Antonopoulos, S. Mikros, M. Mylonopoulou, et al.Rosuvastatin as a novel treatment of non-alcoholic fatty liver disease in hyperlipidemic patients Atherosclerosis, 184 (2006), pp. 233-234 Google Scholar
  33. Abel, J. Feher, E. Dinya, et al.Safety and efficacy of combined ezetimibe/ simvastatin treatment and simvastatin monotherapy in patients with non-alcoholic fatty liver disease Medical Science Monitor, 15 (2009), pp. MS6-MS11
  34. Joseph AE, Saverymuttu SH, al-Sam S, Cook MG, Maxwell JD. Comparison of liver histology with ultrasonography in assessing diffuse parenchymal liver disease. Clin Radiol 1991;43:26-31.
  35. Debongnie JC, Pauls C, Fievez M, Wibin E. Prospective evaluation of the diagnostic accuracy of liver ultrasonography. Gut 1981;22:130-5.
  36. Saverymuttu SH, Joseph AE, Maxwell JD. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed) 1986;292:13-5.
  37. Webb M, Yeshua H, Zelber-Sagi S, Santo E, Brazowski E, Halpern Z, et al. Diagnostic value of a computerized hepatorenal index for sonographic quantification of liver steatosis. AJR Am J Roentgenol 2009;192:909-14.
  38. Valls C, Iannacconne R, Alba E, Murakami T, Hori M, Passariello R, et al. Fat in the liver: Diagnosis and characterization. Eur Radiol 2006;16:2292-30

Corresponding Author

Dr Gagan Gunjan

MD Gen. Medicine