Current Diabetes Reports

, Volume 8, Issue 1, pp 25–30 | Cite as

Nonalcoholic fatty liver disease: Diagnosis and relation to metabolic syndrome and approach to treatment

Article

Abstract

Nonalcoholic fatty liver disease is an increasingly prevalent disorder that spans a range of conditions from hepatic steatosis to cirrhosis. It is commonly associated with obesity and diabetes, two components of the metabolic syndrome. Although hepatic steatosis may be reversible, disease progression appears to be triggered by overproduction of reactive oxygen species and mitochondrial injury in hepatocytes. Evolving treatments are focused on reversing insulin resistance, which underlies many of the metabolic derangements in this disease.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Dunn W, Angulo P, Sanderson S, et al.: Utility of a new model to diagnose an alcohol basis for steatohepatitis. Gastroenterology 2006, 131:1057–1063.PubMedCrossRefGoogle Scholar
  2. 2.
    Roberts EA: Pediatric nonalcoholic fatty liver disease (NAFLD): a “growing” problem? J Hepatol 2007, 46:1133–1142.PubMedCrossRefGoogle Scholar
  3. 3.
    Farrell GC: Drugs and steatohepatitis. Semin Liver Dis 2002, 22:185–194.PubMedCrossRefGoogle Scholar
  4. 4.
    Asselah T, Rubbia-Brandt L, et al.: Steatosis in chronic hepatitis C: why does it really matter? Gut 2006, 55:123–130.PubMedCrossRefGoogle Scholar
  5. 5.
    Kleiner DE, Brunt EM, Van Natta M, et al.: Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005, 41:1313–1321.PubMedCrossRefGoogle Scholar
  6. 6.
    Sanyal AJ, Banas C, Sargeant C, et al.: Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C. Hepatology 2006, 43:682–689.PubMedCrossRefGoogle Scholar
  7. 7.
    Ekstedt M, Franzen LE, Mathiesen UL, et al.: Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006, 44:865–873.PubMedCrossRefGoogle Scholar
  8. 8.
    Adams LA, Sanderson S, Lindor KD, et al.: The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005, 42:132–138.PubMedCrossRefGoogle Scholar
  9. 9.
    Ratziu V, Charlotte F, Heurtier A, et al.: Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005, 128:1898–1906.PubMedCrossRefGoogle Scholar
  10. 10.
    Merriman RB, Ferrell LD, Patti MG, et al.: Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease. Hepatology 2006, 44:874–880.PubMedCrossRefGoogle Scholar
  11. 11.
    Gholam PM, Flancbaum L, Machan JT, et al.: Nonalcoholic fatty liver disease in severely obese subjects. Am J Gastroenterol 2007, 102:399–408.PubMedCrossRefGoogle Scholar
  12. 12.
    Mofrad P, Contos MJ, Haque M, et al.: Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 2003, 37:1286–1292.PubMedCrossRefGoogle Scholar
  13. 13.
    Sorbi D, McGill DB, Thistle JL, et al.: An assessment of the role of liver biopsies in asymptomatic patients with chronic liver test abnormalities. Am J Gastroenterol 2000, 95:3206–3210.PubMedCrossRefGoogle Scholar
  14. 14.
    Skelly MM, James PD, Ryder SD: Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J Hepatol 2001, 35:195–199.PubMedCrossRefGoogle Scholar
  15. 15.
    Graif M, Yanuka M, Baraz M, et al.: Quantitative estimation of attenuation in ultrasound video images: correlation with histology in diffuse liver disease. Invest Radiol 2000, 35:319–324.PubMedCrossRefGoogle Scholar
  16. 16.
    Mathiesen UL, Franzen LE, Aselius H, et al.: Increased liver echogenicity at ultrasound examination reflects degree of steatosis but not of fibrosis in asymptomatic patients with mild/moderate abnormalities of liver transaminases. Dig Liver Dis 2002, 34:516–522.PubMedCrossRefGoogle Scholar
  17. 17.
    Palmentieri B, de Sio I, La Mura V, et al.: The role of bright liver echo pattern on ultrasound B-mode examination in the diagnosis of liver steatosis. Dig Liver Dis 2006, 38:485–489.PubMedCrossRefGoogle Scholar
  18. 18.
    Saadeh S, Younossi ZM, Remer EM, et al.: The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002, 123:745–750.PubMedCrossRefGoogle Scholar
  19. 19.
    Browning JD, Szczepaniak LS, Dobbins R, et al.: Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004, 40:1387–1395.PubMedCrossRefGoogle Scholar
  20. 20.
    Angulo P, Hui JM, Marchesini G, et al.: The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007, 45:846–854.PubMedCrossRefGoogle Scholar
  21. 21.
    Clark JM, Brancati FL, Diehl AM: The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 2003, 98:960–967.PubMedCrossRefGoogle Scholar
  22. 22.
    Angulo P, Keach JC, Batts KP, et al.: Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999, 30:1356–1362.PubMedCrossRefGoogle Scholar
  23. 23.
    Ruhl CE, Everhart JE: Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2003, 124:71–79.PubMedCrossRefGoogle Scholar
  24. 24.
    Gupte P, Amarapurkar D, Agal S, et al.: Non-alcoholic steatohepatitis in type 2 diabetes mellitus. J Gastroenterol Hepatol 2004, 19:854–858.PubMedCrossRefGoogle Scholar
  25. 25.
    Targher G, Bertolini L, Padovani R, et al.: Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007, 30:1212–1218.PubMedCrossRefGoogle Scholar
  26. 26.
    Bellentani S, Saccoccio G, Masutti F, et al.: Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 2000, 132:112–117.PubMedGoogle Scholar
  27. 27.
    Machado M, Marques-Vidal P, Cortez-Pinto H: Hepatic histology in obese patients undergoing bariatric surgery. J Hepatol 2006, 45:600–606.PubMedCrossRefGoogle Scholar
  28. 28.
    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.PubMedGoogle Scholar
  29. 29.
    Fan JG, Li F, Cai XB, et al.: Effects of nonalcoholic fatty liver disease on the development of metabolic disorders. J Gastroenterol Hepatol 2007, 22:1086–1091.PubMedCrossRefGoogle Scholar
  30. 30.
    Browning JD, Horton JD: Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004, 114:147–152.PubMedCrossRefGoogle Scholar
  31. 31.
    Willner IR, Waters B, Patil SR, et al.: Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease. Am J Gastroenterol 2001, 96:2957–2961.PubMedCrossRefGoogle Scholar
  32. 32.
    Chitturi S, Abeygunasekera S, Farrell GC, et al.: NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology 2002, 35:373–379.PubMedCrossRefGoogle Scholar
  33. 33.
    Woodcroft KJ, Hafner MS, Novak RF: Insulin signaling in the transcriptional and posttranscriptional regulation of CYP2E1 expression. Hepatology 2002, 35:263–273.PubMedCrossRefGoogle Scholar
  34. 34.
    Chalasani N, Gorski JC, Asghar MS, et al.: Hepatic cytochrome P450 2E1 activity in nondiabetic patients with nonalcoholic steatohepatitis. Hepatology 2003, 37:544–550.PubMedCrossRefGoogle Scholar
  35. 35.
    Sanyal AJ, Campbell-Sargent C, Mirshahi F, et al.: Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001, 120:1183–1192.PubMedCrossRefGoogle Scholar
  36. 36.
    Gao Z, He Q, Peng B, et al.: Regulation of nuclear translocation of HDAC3 by IkappaBalpha is required for tumor necrosis factor inhibition of peroxisome proliferator-activated receptor gamma function. J Biol Chem 2006, 281:4540–4547.PubMedCrossRefGoogle Scholar
  37. 37.
    Leclercq IA, Da Silva Morais A, Schroyen B, et al.: Insulin resistance in hepatocytes and sinusoidal liver cells: mechanisms and consequences. J Hepatol 2007, 47:142–156.PubMedCrossRefGoogle Scholar
  38. 38.
    Bataller R, Brenner DA: Liver fibrosis. J Clin Invest 2005, 115:209–218.PubMedCrossRefGoogle Scholar
  39. 39.
    Kadowaki T, Yamauchi T, Kubota N, et al.: Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006, 116:1784–1792.PubMedCrossRefGoogle Scholar
  40. 40.
    Hui JM, Hodge A, Farrell GC, et al.: Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 2004, 40:46–54.PubMedCrossRefGoogle Scholar
  41. 41.
    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.PubMedCrossRefGoogle Scholar
  42. 42.
    Wang RT, Koretz RL, Yee HF, Jr: Is weight reduction an effective therapy for nonalcoholic fatty liver? A systematic review. Am J Med 2003, 115:554–559.PubMedCrossRefGoogle Scholar
  43. 43.
    Dixon JB, Bhathal PS, O’Brien PE: Weight loss and non-alcoholic fatty liver disease: falls in gamma-glutamyl transferase concentrations are associated with histologic improvement. Obes Surg 2006, 16:1278–1286.PubMedCrossRefGoogle Scholar
  44. 44.
    Mathurin P, Gonzalez F, Kerdraon O, et al.: The evolution of severe steatosis after bariatric surgery is related to insulin resistance. Gastroenterology 2006, 130:1617–1624.PubMedCrossRefGoogle Scholar
  45. 45.
    Harrison SA, Fincke C, Helinski D, et al.: A pilot study of orlistat treatment in obese, non-alcoholic steatohepatitis patients. Aliment Pharmacol Ther 2004, 20:623–628.PubMedCrossRefGoogle Scholar
  46. 46.
    Zelber-Sagi S, Kessler A, Brazowsky E, et al.: A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2006, 4:639–644.PubMedCrossRefGoogle Scholar
  47. 47.
    Harrison SA, Torgerson S, Hayashi P, et al.: Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2003, 98:2485–2490.PubMedCrossRefGoogle Scholar
  48. 48.
    Lindor KD, Kowdley KV, Heathcote EJ, et al.: Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 2004, 39:770–778.PubMedCrossRefGoogle Scholar
  49. 49.
    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.PubMedCrossRefGoogle Scholar
  50. 50.
    Bugianesi E, Gentilcore E, Manini R, et al.: A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol 2005, 100:1082–1090.PubMedCrossRefGoogle Scholar
  51. 51.
    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.PubMedGoogle Scholar
  52. 52.
    Promrat K, Lutchman G, Uwaifo GI, et al.: A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology 2004, 39:188–196.PubMedCrossRefGoogle Scholar
  53. 53.
    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.PubMedCrossRefGoogle Scholar
  54. 54.
    Rosen CJ: The rosiglitazone story—lessons from an FDA Advisory Committee meeting. N Engl J Med 2007, 357:844–846.PubMedCrossRefGoogle Scholar
  55. 55.
    Schupp M, Janke J, Clasen R, et al.: Angiotensin type 1 receptor blockers induce peroxisome proliferators-activated receptor-gamma activity. Circulation 2004, 109:2054–2057.PubMedCrossRefGoogle Scholar
  56. 56.
    Leung PS, Suen PM, Ip SP, et al.: Expression and localization of AT1 receptors in hepatic Kupffer cells: its potential role in regulating a fibrogenic response. Regul Pept 2003, 116:61–69.PubMedCrossRefGoogle Scholar
  57. 57.
    Yang L, Bataller R, Dulyx J, et al.: Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice. J Hepatol 2005, 43:317–323.PubMedCrossRefGoogle Scholar
  58. 58.
    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.PubMedCrossRefGoogle Scholar
  59. 59.
    Fujita K, Yoneda M, Wada K, et al.: Telmisartan, an angiotensin II type 1 receptor blocker, controls progress of nonalcoholic steatohepatitis in rats. Dig Dis Sci 2007, in press.Google Scholar
  60. 60.
    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.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2008

Authors and Affiliations

  1. 1.Departments of Medicine and PharmacologyUniversity of VermontBurlingtonUSA

Personalised recommendations