Nonalcoholic Fatty Liver Disease

Jae Sung Ko

doi:10.4166/kjg.2010.56.1.6

Journal List > Korean J Gastroenterol > v.56(1) > 1006760

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Ko: Nonalcoholic Fatty Liver Disease

Review

Korean J Gastroenterol 2010;56(1):6-14.

Published online: 21 February 2010

DOI: https://doi.org/10.4166/kjg.2010.56.1.6

Nonalcoholic Fatty Liver Disease

Jae Sung Ko, M.D.

Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea

Correspondence to: Jae Sung Ko, M.D. Department of Pediatrics, Seoul National University Hospital, 28, Yongondong, Jongro-gu, Seoul 110-744, Korea Tel: +82-2-2072-2197, Fax: +82-2-743-3455 E-mail: kojs@snu.ac.kr

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is commonly associated with obesity. The spectrum of NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Fructose ingestion, visceral obesity, and metabolic syndrome are risk factors for liver fibrosis. NAFLD is characterized by two steps of liver injury: intrahepatic lipid accumulation in the setting of insulin resistance, and inflammatory progression to NASH by oxidative stress and inflammatory mediators. Noninvasive methods (e.g., abdominal ultrasonography) are safe ways to support a diagnosis of hepatic steatosis, but liver biopsy remains the gold standard for accurate diagnosis and staging of NASH. Pediatric NASH often displays a histologic pattern distinct from that found in adults. Lifestyle modification through diet and exercise should be at-tempted in patients diagnosed with NAFLD.

Keywords: Nonalcoholic fatty liver disease, Steatohepatitis, Obesity

REFERENCES

1. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto un-named disease. Mayo Clin Proc. 1980; 55:434–438.

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

3. Bellentani S, Scaglioni F, Marino M, Bedogni G. Epidemiology of non-alcoholic fatty liver disease. Dig Dis. 2010; 28:155–161.

4. Browning JD. Statins and hepatic steatosis: perspectives from the dallas heart study. Hepatology. 2006; 44:466–471.

5. Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: the dionysos nutrition and liver study. Hepatology. 2005; 42:44–52.

6. Park SH, Jeon WK, Kim SH, et al. Prevalence and risk factors of non-alcoholic fatty liver disease among Korean adults. J Gastroenterol Hepatol. 2006; 21:138–143.

7. Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology. 1990; 12:1106–1110.

8. Park HS, Han JH, Choi KM, Kim SM. Relation between elevated serum alanine aminotransferase and metabolic syndrome in Korean adolescents. Am J Clin Nutr. 2005; 82:1046–1051.

9. Strauss RS, Barlow SE, Dietz WH. Prevalence of abnormal serum aminotransferase values in overweight and obese adolescents. J Pediatr. 2000; 136:727–733.

10. Tominaga K, Kurata JH, Chen YK, et al. Prevalence of fatty liver in Japanese children and relationship to obesity. An epi-demiological ultrasonographic survey. Dig Dis Sci. 1995; 40:2002–2009.

11. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006; 118:1388–1393.

12. Schwimmer JB, McGreal N, Deutsch R, Finegold MJ, Lavine JE. Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents. Pediatrics. 2005; 115:e561–565.

13. Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology. 2002; 122:1649–1657.

14. Shimizu I, Inoue H, Yano M, et al. Estrogen receptor levels and lipid peroxidation in hepatocellular carcinoma with hepatitis C virus infection. Liver. 2001; 21:342–349.

15. Petersen KF, Dufour S, Feng J, et al. Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men. Proc Natl Acad Sci USA. 2006; 103:18273–18277.

16. Deurenberg P, Deurenberg-Yap M, Guricci S. Asians are different from Caucasians and from each other in their body mass index/body fat per cent relationship. Obes Rev. 2002; 3:141–146.

17. Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008; 40:1461–1465.

18. Petersen KF, Dufour S, Hariri A, et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N Engl J Med. 2010; 362:1082–1089.

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

20. Manco M, Marcellini M, Devito R, Comparcola D, Sartorelli MR, Nobili V. Metabolic syndrome and liver histology in paediatric non-alcoholic steatohepatitis. Int J Obes (Lond). 2008; 32:381–387.

21. Stranges S, Dorn JM, Muti P, et al. Body fat distribution, relative weight, and liver enzyme levels: a population-based study. Hepatology. 2004; 39:754–763.

22. Jeong SK, Kim YK, Park JW, Shin YJ, Kim DS. Impact of visceral fat on the metabolic syndrome and nonalcoholic fatty liver disease. J Korean Med Sci. 2008; 23:789–795.

23. van der Poorten D, Milner KL, Hui J, et al. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology. 2008; 48:449–457.

24. Manco M, Bedogni G, Marcellini M, et al. Waist circumference correlates with liver fibrosis in children with non-alcoholic steatohepatitis. Gut. 2008; 57:1283–1287.

25. Nobili V, Marcellini M, Devito R, et al. NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice. Hepatology. 2006; 44:458–465.

26. Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S. Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation. 2008; 118:277–283.

27. Choi SY, Kim D, Kim HJ, et al. The relation between non-alcoholic fatty liver disease and the risk of coronary heart disease in Koreans. Am J Gastroenterol. 2009; 104:1953–1960.

28. Brea A, Mosquera D, Martin E, Arizti A, Cordero JL, Ros E. Nonalcoholic fatty liver disease is associated with carotid atherosclerosis: a case-control study. Arterioscler Thromb Vasc Biol. 2005; 25:1045–1050.

29. Demirciog ¨ lu F, Koç yig ¨ it it A, Arslan N, Cakmakç i H, Hizli S, Sedat AT. Intima-media thickness of carotid artery and susceptibility to atherosclerosis in obese children with non-alcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2008; 47:68–75.

30. Tetri LH, Basaranoglu M, Brunt EM, Yerian LM, Neuschwander-Tetri BA. Severe NAFLD with hepatic nec-roinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. Am J Physiol Gastrointest Liver Physiol. 2008; 295:G987–995.

31. Abid A, Taha O, Nseir W, Farah R, Grosovski M, Assy N. Soft drink consumption is associated with fatty liver disease independent of metabolic syndrome. J Hepatol. 2009; 51:918–924.

32. Abdelmalek MF, Suzuki A, Guy C, et al. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology. 2010; 51:1961–1971.

33. Fassio E, Alvarez E, Dominguez N, Landeira G, Longo C. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology. 2004; 40:820–826.

34. Adams LA, Lymp JF, St Sauver J, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005; 129:113–121.

35. Angulo P. Longterm mortality in nonalcoholic fatty liver disease: is liver histology of any prognostic significance? Hepatology. 2010; 51:373–375.

36. Söderberg C, Stå l P, Askling J, et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology. 2010; 51:595–602.

37. Rafiq N, Bai C, Fang Y, et al. Longterm follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol. 2009; 7:234–238.

38. Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, Benson JT, Enders FB, Angulo P. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut. 2009; 58:1538–1544.

39. Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology. 1998; 114:842–845.

40. Lewis JR, Mohanty SR. Nonalcoholic fatty liver disease: a review and update. Dig Dis Sci. 2010; 55:560–578.

41. Schwarz JM, Neese RA, Turner S, Dare D, Hellerstein MK. Short-term alterations in carbohydrate energy intake in humans. Striking effects on hepatic glucose production, de novo lipogenesis, lipolysis, and whole-body fuel selection. J Clin Invest. 1995; 96:2735–2743.

42. Lim JS, Mietus-Snyder M, Valente A, Schwarz JM, Lustig RH. The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome. Nat Rev Gastroenterol Hepatol. 2010; 7:251–264.

43. Charlton M, Sreekumar R, Rasmussen D, Lindor K, Nair KS. Apolipoprotein synthesis in nonalcoholic steatohepatitis. Hepatology. 2002; 35:898–904.

44. Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest. 2004; 114:147–152.

45. Cai D, Yuan M, Frantz DF, et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 2005; 11:183–190.

46. Crespo J, Cayó n A, Ferná ndez-Gil P, et al. Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology. 2001; 34:1158–1163.

47. Targher G, Bertolini L, Rodella S, et al. Associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease. Clin Endocrinol (Oxf). 2006; 64:679–683.

48. Baffy G. Kupffer cells in non-alcoholic fatty liver disease: the emerging view. J Hepatol. 2009; 51:212–223.

49. Pé rez-Carreras M, Del Hoyo P, Martin MA, et al. Defective hepatic mitochondrial respiratory chain in patients with non-alcoholic steatohepatitis. Hepatology. 2003; 38:999–1007.

50. Vendemiale G, Grattagliano I, Caraceni P, et al. Mitochondrial oxidative injury and energy metabolism alteration in rat fatty liver: effect of the nutritional status. Hepatology. 2001; 33:808–815.

51. Sanyal AJ, Campbell-Sargent C, Mirshahi F, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology. 2001; 120:1183–1192.

52. Patton HM, Lavine JE, Van Natta ML, et al. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology. 2008; 135:1961–1971.

53. Haukeland JW, Damås JK, Konopski Z, et al. Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2. J Hepatol. 2006; 44:1167–1174.

54. Suzuki A, Angulo P, Lymp J, Li D, Satomura S, Lindor K. Hyaluronic acid, an accurate serum marker for severe hepatic fibrosis in patients with non-alcoholic fatty liver disease. Liver Int. 2005; 25:779–786.

55. Ratziu V, Massard J, Charlotte F, et al. Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol. 2006; 6:6.

56. 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.

57. Patton HM, Sirlin C, Behling C, Middleton M, Schwimmer JB, Lavine JE. Pediatric nonalcoholic fatty liver disease: a critical appraisal of current data and implications for future research. J Pediatr Gastroenterol Nutr. 2006; 43:413–427.

58. Osawa H, Mori Y. Sonographic diagnosis of fatty liver using a histogram technique that compares liver and renal cortical echo amplitudes. J Clin Ultrasound. 1996; 24:25–29.

59. Park SH, Kim PN, Kim KW, et al. Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment. Radiology. 2006; 239:105–112.

60. Lee JY, Kim KM, Lee SG, et al. Prevalence and risk factors of non-alcoholic fatty liver disease in potential living liver donors in Korea: a review of 589 consecutive liver biopsies in a single center. J Hepatol. 2007; 47:239–244.

61. Fishbein M, Castro F, Cheruku S, et al. Hepatic MRI for fat quantitation: its relationship to fat morphology, diagnosis, and ultrasound. J Clin Gastroenterol. 2005; 39:619–625.

62. Szczepaniak LS, Nurenberg P, Leonard D, et al. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab. 2005; 288:E462–468.

63. Yoneda M, Mawatari H, Fujita K, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD). Dig Liver Dis. 2008; 40:371–378.

64. Yin M, Talwalkar JA, Glaser KJ, et al. Assessment of hepatic fibrosis with magnetic resonance elastography. Clin Gastroenterol Hepatol. 2007; 5:1207–1213.

65. 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.

66. Loomba R, Sirlin CB, Schwimmer JB, Lavine JE. Advances in pediatric nonalcoholic fatty liver disease. Hepatology. 2009; 50:1282–1293.

67. Schwimmer JB, Behling C, Newbury R, et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology. 2005; 42:641–649.

68. Ko JS, Yoon JM, Yang HR, et al. Clinical and histological features of nonalcoholic fatty liver disease in children. Dig Dis Sci. 2009; 54:2225–2230.

69. Petersen KF, Dufour S, Befroy D, Lehrke M, Hendler RE, Shulman GI. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes. 2005; 54:603–608.

70. Huang MA, Greenson JK, Chao C, et al. One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study. Am J Gastroenterol. 2005; 100:1072–1081.

71. Andersen T, Gluud C, Franzmann MB, Christoffersen P. Hepatic effects of dietary weight loss in morbidly obese subjects. J Hepatol. 1991; 12:224–229.

72. Sanyal AJ; American Gastroenterological Association. AGA technical review on nonalcoholic fatty liver disease. Gastroenterology. 2002; 123:1705–1725.

73. Reinehr T, Schmidt C, Toschke AM, Andler W. Lifestyle intervention in obese children with non-alcoholic fatty liver disease: 2-year follow-up study. Arch Dis Child. 2009; 94:437–442.

74. Benjaminov O, Beglaibter N, Gindy L, et al. The effect of a low-carbohydrate diet on the nonalcoholic fatty liver in morbidly obese patients before bariatric surgery. Surg Endosc. 2007; 21:1423–1427.

75. Samaha FF, Iqbal N, Seshadri P, et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med. 2003; 348:2074–2081.

76. Ebbeling CB, Leidig MM, Feldman HA, Lovesky MM, Ludwig DS. Effects of a low-glycemic load vs low-fat diet in obese young adults: a randomized trial. JAMA. 2007; 297:2092–2102.

77. Shai I, Schwarzfuchs D, Henkin Y, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008; 359:229–241.

78. Boulé NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a metaanalysis of controlled clinical trials. JAMA. 2001; 286:1218–1227.

79. Hannukainen JC, Nuutila P, Borra R, et al. Increased physical activity decreases hepatic free fatty acid uptake: a study in human monozygotic twins. J Physiol. 2007; 578:347–358.

80. St George A, Bauman A, Johnston A, Farrell G, Chey T, George J. Independent effects of physical activity in patients with nonalcoholic fatty liver disease. Hepatology. 2009; 50:68–76.

81. Johnson NA, Sachinwalla T, Walton DW, et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology. 2009; 50:1105–1112.

82. Hasegawa T, Yoneda M, Nakamura K, Makino I, Terano A. Plasma transforming growth factor-beta1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Aliment Pharmacol Ther. 2001; 15:1667–1672.

83. Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol. 2003; 98:2485–2490.

84. Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM. Pioglitazone, vitamin E, or placebo for non-alcoholic steatohepatitis. N Engl J Med. 2010; 362:1675–1685.

85. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M, Melchionda N. Metformin in non-alcoholic steatohepatitis. Lancet. 2001; 358:893–894.

86. 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.

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

88. 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.

89. Aithal GP, Thomas JA, Kaye PV, et al. Randomized, place-bo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology. 2008; 135:1176–1184.

90. Lindor KD, Kowdley KV, Heathcote EJ, et al. Ursodeoxy-cholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology. 2004; 39:770–778.

91. Kral JG, Thung SN, Biron S, et al. Effects of surgical treatment of the metabolic syndrome on liver fibrosis and cirrhosis. Surgery. 2004; 135:48–58.

92. 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.

TOOLS

Similar articles