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Treatment strategies in nonalcoholic fatty liver disease

Nature Clinical Practice Gastroenterology & Hepatology volume 2, pages 148–155 (2005)Cite this article

Abstract

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized health problem. Increased fat accumulation in the liver is observed in 20–30% of the population in the Western world, and in approximately 10% of this cohort it is associated with nonalcoholic steatohepatitis, which is characterized by inflammation and fibrosis. Disease presentation of NAFLD ranges from asymptomatic disease to cirrhosis with the complication of liver failure and hepatocellular carcinoma. NAFLD is suspected on the basis of various clinical aspects (an elevated alanine aminotransferase concentration, presence of obesity and diabetes) that alone are not sufficient to establish diagnosis or prognosis. The major diagnostic procedure is liver biopsy, which allows assessment of liver injury. In most cases, NAFLD is associated with insulin resistance, which is therefore the target of most current NAFLD treatment modalities. Various treatment strategies such as weight loss and/or exercise, thiazolidinediones, metformin, lipid-lowering agents and antioxidants have been studied. So far, no single intervention has convincingly improved liver histology. It is recommended that patients at high risk of developing advanced liver disease, and who are not part of controlled studies, should receive nutritional counseling and take physical exercise to achieve moderate weight loss and improve insulin sensitivity.

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References

  1. Ludwig J et al. (1980) Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 55: 434–438

    CAS  PubMed  Google Scholar 

  2. Angulo P (2002) Nonalcoholic fatty liver disease. N Engl J Med 346: 1221–1231

    Article  CAS  PubMed  Google Scholar 

  3. Marchesini G et al. (2001) Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 50: 1844–1850

    Article  CAS  PubMed  Google Scholar 

  4. Sanyal AJ (2005) Mechanisms of disease: pathogenesis of nonalcoholic fatty liver disease. Nat Clin Pract Gastroenterol Hepatol 2: 46–53

    Article  CAS  PubMed  Google Scholar 

  5. Browning JD and Horton JD (2004) Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114: 147–152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Neuschwander-Tetri BA and Caldwell SH (2003) Nonalcoholic steatohepatitis: Summary of an AASLD single topic conference. Hepatology 37: 1202–1219

    Article  PubMed  Google Scholar 

  7. Tajiri K et al. (1997) Nonalcoholic steatohepatitis masquerading as autoimmune hepatitis. J Clin Gastroenterol 25: 538–540

    Article  CAS  PubMed  Google Scholar 

  8. Saadeh S et al. (2002) The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 123: 745–750

    Article  PubMed  Google Scholar 

  9. Brunt EM et al. (1999) Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94: 2467–2474

    Article  CAS  PubMed  Google Scholar 

  10. Matteoni CA et al. (1999) Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 116: 1413–1419

    Article  CAS  PubMed  Google Scholar 

  11. Dam-Larsen S et al. (2004) Long term prognosis of fatty liver: risk of chronic liver disease and death. Gut 53: 750–755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jepsen P et al. (2003) Prognosis of patients with a diagnosis of fatty liver—a registry-based cohort study. Hepatogastroenterology 50: 2101–2104

    PubMed  Google Scholar 

  13. Powell EE et al. (1990) The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 11: 74–80

    Article  PubMed  Google Scholar 

  14. Harrison SA et al. (2003) The natural history of nonalcoholic fatty liver disease: a clinical histopathological study. Am J Gastroenterol 98: 2042–2047

    Article  PubMed  Google Scholar 

  15. Fassio E et al. (2004) Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology 40: 820–826

    PubMed  Google Scholar 

  16. Caldwell SH et al. (1999) Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology 29: 664–669

    Article  CAS  PubMed  Google Scholar 

  17. Angulo P et al. (1999) Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 30: 1356–1362

    Article  CAS  PubMed  Google Scholar 

  18. Gramlich T et al. (2004) Pathologic features associated with fibrosis in nonalcoholic fatty liver disease. Hum Pathol 35: 196–199

    Article  PubMed  Google Scholar 

  19. Younossi ZM et al. (2004) Nonalcoholic fatty liver disease in patients with type 2 diabetes. Clin Gastroenterol Hepatol 2: 262–265

    Article  PubMed  Google Scholar 

  20. Ratziu V et al. (2000) Liver fibrosis in overweight patients. Gastroenterology 118: 1117–1123

    Article  CAS  PubMed  Google Scholar 

  21. Dixon JB et al. (2001) Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 121: 91–100

    Article  CAS  PubMed  Google Scholar 

  22. Drenick EJ et al. (1970) Effect on hepatic morphology of treatment of obesity by fasting, reducing diets and small-bowel bypass. N Engl J Med 282: 829–834

    Article  CAS  PubMed  Google Scholar 

  23. Rozental P et al. (1967) Liver morphology and function tests in obesity and during total starvation. Am J Dig Dis 12: 198–208

    Article  CAS  PubMed  Google Scholar 

  24. Luyckx FH et al. (1998) Liver abnormalities in severely obese subjects: effect of drastic weight loss after gastroplasty. Int J Obes Relat Metab Disord 22: 222–226

    Article  CAS  PubMed  Google Scholar 

  25. Andersen T et al. (1991) Hepatic effects of dietary weight loss in morbidly obese subjects. J Hepatol 12: 224–229

    Article  CAS  PubMed  Google Scholar 

  26. Wang RT et al. (2003) Is weight reduction an effective therapy for nonalcoholic fatty liver? A systematic review. Am J Med 115: 554–559

    Article  PubMed  Google Scholar 

  27. Park HS et al. (1995) Effect of weight control on hepatic abnormalities in obese patients with fatty liver. J Korean Med Sci 10: 414–421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ueno T et al. (1997) Therapeutic effects of restricted diet and exercise in obese patients with fatty liver. J Hepatol 27: 103–107

    Article  CAS  PubMed  Google Scholar 

  29. Ranlov I and Hardt F (1990) Regression of liver steatosis following gastroplasty or gastric bypass for morbid obesity. Digestion 47: 208–214

    Article  CAS  PubMed  Google Scholar 

  30. Dixon JB et al. (2004) Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss. Hepatology 39: 1647–1654

    Article  PubMed  Google Scholar 

  31. Harrison SA et al. (2003) Orlistat in the treatment of NASH: a case series. Am J Gastroenterol 98: 926–930

    Article  CAS  PubMed  Google Scholar 

  32. Harrison SA et al. (2004) A pilot study of orlistat treatment in obese, non-alcoholic steatohepatitis patients. Aliment Pharmacol Ther 20: 623–628

    Article  CAS  PubMed  Google Scholar 

  33. Kral JG et al. (2004) Effects of surgical treatment of the metabolic syndrome on liver fibrosis and cirrhosis. Surgery 135: 48–58

    Article  PubMed  Google Scholar 

  34. Baltasar A et al. (2004) Clinical hepatic impairment after the duodenal switch. Obes Surg 14: 77–83

    Article  PubMed  Google Scholar 

  35. Yki-Jarvinen H (2004) Thiazolidinediones. N Engl J Med 351: 1106–1118

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  37. Promrat K et al. (2004) A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology 39: 188–196

    Article  CAS  PubMed  Google Scholar 

  38. Neuschwander-Tetri BA et al. (2003) Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology 38: 1008–1017

    Article  CAS  PubMed  Google Scholar 

  39. Marchesini G et al. (2001) Metformin in non-alcoholic steatohepatitis. Lancet 358: 893–894

    Article  CAS  PubMed  Google Scholar 

  40. Uygun A et al. (2004) Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 19: 537–544

    Article  CAS  PubMed  Google Scholar 

  41. Nair S et al. (2004) Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther 20: 23–28

    Article  CAS  PubMed  Google Scholar 

  42. Laurin J et al. (1996) Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: a pilot study. Hepatology 23: 1464–1467

    Article  CAS  PubMed  Google Scholar 

  43. Basaranoglu M et al. (1999) A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis. J Hepatol 31: 384

    Article  CAS  PubMed  Google Scholar 

  44. Rallidis LS et al. (2004) Pravastatin in patients with nonalcoholic steatohepatitis: results of a pilot study. Atherosclerosis 174: 193–196

    Article  CAS  PubMed  Google Scholar 

  45. Harrison SA et al. (2003) Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 98: 2485–2490

    Article  CAS  PubMed  Google Scholar 

  46. Adams LA and Angulo P (2003) Vitamins E and C for the treatment of NASH: duplication of results but lack of demonstration of efficacy. Am J Gastroenterol 98: 2348–2350

    Article  CAS  PubMed  Google Scholar 

  47. Hasegawa T et al. (2001) Plasma transforming growth factor-beta1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Aliment Pharmacol Ther 15: 1667–1672

    Article  CAS  PubMed  Google Scholar 

  48. Sanyal AJ et al. (2004) A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 2: 1107–1115

    Article  CAS  PubMed  Google Scholar 

  49. Abdelmalek MF et al. (2001) Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am J Gastroenterol 96: 2711–2717

    Article  CAS  PubMed  Google Scholar 

  50. Lindor KD et al. (2004) Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 39: 770–778

    Article  CAS  PubMed  Google Scholar 

  51. Yoshiji H et al. (2001) Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats. Hepatology 34: 745–750

    Article  CAS  PubMed  Google Scholar 

  52. Yokohama S et al. (2004) Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology 40: 1222–1225

    Article  CAS  PubMed  Google Scholar 

  53. Tilg H and Diehl AM (2000) Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med 343: 1467–1476

    Article  CAS  PubMed  Google Scholar 

  54. Satapathy SK et al. (2004) Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. Am J Gastroenterol 99: 1946–1952

    Article  CAS  PubMed  Google Scholar 

  55. Colditz GA et al. (1995) Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 122: 481–486

    Article  CAS  PubMed  Google Scholar 

  56. Eriksson S et al. (1986) Nonalcoholic steatohepatitis in obesity: a reversible condition. Acta Med Scand 220: 83–88

    Article  CAS  PubMed  Google Scholar 

  57. Silverman EM et al. (1995) Regression of hepatic steatosis in morbidly obese persons after gastric bypass. Am J Clin Pathol 104: 23–3155

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors' work is supported by the Austrian Science Fund.

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Authors and Affiliations

  1. Department of Medicine, Academic Teaching Hospital Hall in Tyrol,

    Herbert Tilg

  2. Division of Gastroenterology and Hepatology, Innsbruck Medical University, Innsbruck, Austria

    Herbert Tilg

  3. faculty member of the Division of Gastroenterology and Hepatology, Innsbruck Medical University, Austria

    Arthur Kaser

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Correspondence to Herbert Tilg.

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Tilg, H., Kaser, A. Treatment strategies in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2, 148–155 (2005). https://doi.org/10.1038/ncpgasthep0116

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  • DOI: https://doi.org/10.1038/ncpgasthep0116

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