Skip to main content

Advertisement

Log in

Nonalcoholic fatty liver disease as a component of the metabolic syndrome

  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Nonalcoholic fatty liver disease (NAFLD) is an important cause of liver-related morbidity and mortality. The association between NAFLD and the metabolic syndrome is well established: the presence of the metabolic syndrome signifies advanced histology in NAFLD patients. Emerging data indicate that patients with NAFLD have a significantly higher prevalence of cardiovascular disease. This article reviews the definitions of the two syndromes, their association, and the cardiovascular risk conferred by both when they occur separately and together. This review also discusses management options for the syndromes, including treating the individual components of the metabolic syndrome in NAFLD patients.

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.

Similar content being viewed by others

References and Recommended Reading

  1. Contos MJ, Sanyal AJ: The clinicopathologic spectrum and management of nonalcoholic fatty liver disease. Adv Anat Pathol 2002, 9:37–51.

    Article  PubMed  Google Scholar 

  2. Reaven GM: Role of insulin resistance in human disease. Diabetes 1988, 37:1595–1600.

    Article  PubMed  CAS  Google Scholar 

  3. Flegal KM, Carroll MD, Ogden CL, Johnson CL: Prevalence and trends in obesity among US adults, 1999–2000. JAMA 2002, 288:1723–1727.

    Article  PubMed  Google Scholar 

  4. Ford ES, Giles WH, Dietz WH: Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002, 287:356–359.

    Article  PubMed  Google Scholar 

  5. Pourshams A, Malekzadeh R, Monavvari A, et al.: Prevalence and etiology of persistently elevated alanine aminotransferase levels in healthy Iranian blood donors. J Gastroenterol Hepatol 2005, 20:229–233.

    Article  PubMed  Google Scholar 

  6. Schwimmer JB, Deutsch R, Kahen T, et al.: Prevalence of fatty liver in children and adolescents. Pediatrics 2006, 118:1388–1393.

    Article  PubMed  Google Scholar 

  7. Marchesini G, Bugianesi E, Forlani G, et al.: Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003, 37:917–923.

    Article  PubMed  Google Scholar 

  8. Liangpunsakul S, Chalasani N: Unexplained elevations in alanine aminotransferase in individuals with the metabolic syndrome: results from the third National Health and Nutrition Survey (NHANES III). Am J Med Sci 2005, 329:111–116.

    Article  PubMed  Google Scholar 

  9. Fan JG, Zhu J, Li XJ, et al.: Fatty liver and the metabolic syndrome among Shanghai adults. J Gastroenterol Hepatol 2005, 20:1825–1832.

    Article  PubMed  Google Scholar 

  10. Hamaguchi M, Kojima T, Takeda N, et al.: The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med 2005, 143:722–728.

    PubMed  CAS  Google Scholar 

  11. Galassi A, Reynolds K, He J: Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. Am J Med 2006, 119:812–819.

    Article  PubMed  CAS  Google Scholar 

  12. Matteoni CA, Younossi ZM, Gramlich T, et al.: Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999, 116:1413–1419.

    Article  PubMed  CAS  Google Scholar 

  13. Ioannou GN, Weiss NS, Boyko EJ, et al.: Elevated serum alanine aminotransferase activity and calculated risk of coronary heart disease in the United States. Hepatology 2006, 43:1145–1151.

    Article  PubMed  CAS  Google Scholar 

  14. Targher G, Bertolini L, Poli F, et al.: Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes 2005, 54:3541–3546.

    Article  PubMed  CAS  Google Scholar 

  15. Eckel RH, Grundy SM, Zimmet PZ: The metabolic syndrome. Lancet 2005, 365:1415–1428.

    Article  PubMed  CAS  Google Scholar 

  16. Musso G, Gambino R, Durazzo M, et al.: Adipokines in NASH: postprandial lipid metabolism as a link between adiponectin and liver disease. Hepatology 2005, 42:1175–1183.

    Article  PubMed  CAS  Google Scholar 

  17. Hui JM, Hodge A, Farrell GC, et al.: Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 2004, 40:46–54.

    Article  PubMed  CAS  Google Scholar 

  18. Pischon T, Girman CJ, Hotamisligil GS, et al.: Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004, 291:1730–1737.

    Article  PubMed  CAS  Google Scholar 

  19. Kang H, Greenson JK, Omo JT, et al.: Metabolic syndrome is associated with greater histologic severity, higher carbohydrate, and lower fat diet in patients with NAFLD. Am J Gastroenterol 2006, 101:2247–2253.

    Article  PubMed  CAS  Google Scholar 

  20. Grundy SM, Cleeman JI, Daniels SR, et al.; American Heart Association, National Heart, Lung, and Blood Institute: Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005, 112:2735–2752.

    Article  PubMed  Google Scholar 

  21. Palmer M, Schaffner F: Effect of weight reduction on hepatic abnormalities in overweight patients. Gastroenterology 1990, 99:1408–1413.

    PubMed  CAS  Google Scholar 

  22. Zelber-Sagi S, Kessler A, Brazowsky E, et al.: A doubleblind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2006, 4:639–644.

    Article  PubMed  CAS  Google Scholar 

  23. Horvath TL: Endocannabinoids and the regulation of body fat: the smoke is clearing. J Clin Invest 2003, 112:323–326.

    Article  PubMed  CAS  Google Scholar 

  24. Hollander P: Endocannabinoid blockade for improving glycemic control and lipids in patients with type 2 diabetes mellitus. Am J Med 2007, 120(Suppl):S18–S28, discussion S29–S32.

    Article  PubMed  CAS  Google Scholar 

  25. Silverman EM, Sapala JA, Appelman HD: Regression of hepatic steatosis in morbidly obese persons after gastric bypass. Am J Clin Pathol 1995, 104:23–31.

    PubMed  CAS  Google Scholar 

  26. Luyckx FH, Desaive C, Thiry A, et al.: Liver abnormalities in severely obese subjects: effect of drastic weight loss after gastroplasty. Int J Obes Relat Metab Disord 1998, 22:222–226.

    Article  PubMed  CAS  Google Scholar 

  27. Klein S, Mittendorfer B, Eagon JC, et al.: Gastric bypass surgery improves metabolic and hepatic abnormalities associated with nonalcoholic fatty liver disease. Gastroenterology 2006, 130:1564–1572.

    Article  PubMed  CAS  Google Scholar 

  28. Barker KB, Palekar NA, Bowers SP, et al.: Non-alcoholic steatohepatitis: effect of Roux-en-Y gastric bypass surgery. Am J Gastroenterol 2006, 101:368–373.

    Article  PubMed  Google Scholar 

  29. Rallidis LS, Drakoulis CK, Parasi AS: Pravastatin in patients with nonalcoholic steatohepatitis: results of a pilot study. Atherosclerosis 2004, 174:193–196.

    Article  PubMed  CAS  Google Scholar 

  30. Horlander JC, Kwo PY, Cummings OW: Atorvastatin for the treatment of NASH [abstract]. Gastroenterology 2001, 120:A544.

    Article  Google Scholar 

  31. Chalasani N, Aljadhey H, Kesterson J, et al.: Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroenterology 2004, 126:1287–1292.

    Article  PubMed  CAS  Google Scholar 

  32. Vuppalanchi R, Teal E, 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 2005, 329:62–65.

    Article  PubMed  Google Scholar 

  33. Vlachogiannakos J, Tang AK, Patch D, Burroughs AK: Angiotensin converting enzyme inhibitors and angiotensin II antagonists as therapy in chronic liver disease. Gut 2001, 49:303–308.

    Article  PubMed  CAS  Google Scholar 

  34. Hirose A, Ono M, Saibara T, et al.: Angiotensin II type 1 receptor blocker inhibits fibrosis in rat nonalcoholic steatohepatitis. Hepatology 2007, 45:1375–1381.

    Article  PubMed  CAS  Google Scholar 

  35. Yokohama S, Yoneda M, Haneda M, et al.: Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology 2004, 40:1222–1225.

    Article  PubMed  CAS  Google Scholar 

  36. Caldwell SH, Hespenheide EE, Redick JA, et al.: A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis. Am J Gastroenterol 2001, 96:519–525.

    Article  PubMed  CAS  Google Scholar 

  37. Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, et al.: Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-[gamma] ligand rosiglitazone. Hepatology 2003, 38:1008–1017.

    PubMed  CAS  Google Scholar 

  38. Promrat K, Lutchman G, Uwaifo GI, et al.: A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology 2004, 39:188–196.

    Article  PubMed  CAS  Google Scholar 

  39. Shadid S, Jensen MD: Effect of pioglitazone on biochemical indices of non-alcoholic fatty liver disease in upper body obesity. Clin Gastroenterol Hepatol 2003, 1:384–387.

    Article  PubMed  CAS  Google Scholar 

  40. Sanyal AJ, Mofrad PS, Contos MJ, et al.: A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 2004, 2:1107–1115.

    Article  PubMed  CAS  Google Scholar 

  41. Belfort R, Harrison SA, Brown K, et al.: A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006, 355:2297–2307.

    Article  PubMed  CAS  Google Scholar 

  42. Ratziu V, Charlotte F, Jacqueminet S, et al.: A one year randomized, placebo-controlled, double-blind trial of rosiglitazone in nonalcoholic steatohepatitis: results of the FLIRT pilot trial [abstract]. Hepatology 2006, 44(Suppl):201A.

    Google Scholar 

  43. Nissen SE, Wolski K: Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007, 356:2457–2471.

    Article  PubMed  CAS  Google Scholar 

  44. Home PD, Pocock SJ, Beck-Nielsen H, et al.; RECORD Study Group: Rosiglitazone evaluated for cardiovascular outcomes-an interim analysis. N Engl J Med 2007, 357:28–38.

    Article  PubMed  CAS  Google Scholar 

  45. Marchesini G, Brizi M, Bianchi G, et al.: Metformin in non-alcoholic steatohepatitis. Lancet 2001, 358:893–894.

    Article  PubMed  CAS  Google Scholar 

  46. Nair S, Diehl AM, Wiseman M, et al.: Metformin in the treatment of non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2004, 20:23–38.

    Article  PubMed  CAS  Google Scholar 

  47. Uygun A, Kadayifci A, Isik AT, et al.: Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2004, 19:537–544.

    Article  PubMed  CAS  Google Scholar 

  48. Bugianesi E, Gentilcore E, Manini R, et al.: A randomized controlled trial of metformin vs. vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol 2005, 100:1082–1090.

    Article  PubMed  CAS  Google Scholar 

  49. Schwimmer JB, Middleton MS, Deutsch R, Lavine JE: A phase 2 clinical trial of metformin as a treatment for nondiabetic paediatric non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2005, 21:871–879.

    Article  PubMed  CAS  Google Scholar 

  50. Loomba R, Lutchman G, Kleiner D, et al.: Pilot study of metformin in patients with nonalcoholic steatohepatitis [abstract]. Hepatology 2006, 44(Suppl):260A.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Naga Chalasani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khashab, M.A., Liangpunsakul, S. & Chalasani, N. Nonalcoholic fatty liver disease as a component of the metabolic syndrome. Curr Gastroenterol Rep 10, 73–80 (2008). https://doi.org/10.1007/s11894-008-0012-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-008-0012-0

Keywords

Navigation