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Table of Contents
Vol. 29, No. 2, 2011
Issue release date: July 2011
Dig Dis 2011;29:202–210
(DOI:10.1159/000323886)

ASH and NASH

Scaglioni F. · Ciccia S. · Marino M. · Bedogni G. · Bellentani S.
aLiver Center, Gastroenterologia, Distretto di Carpi, Azienda USL di Modena, Carpi, and bLiver Research Center, Trieste, Italy

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Abstract

Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) have a similar pathogenesis and histopathology but a different etiology and epidemiology. NASH and ASH are advanced stages of non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD). NAFLD is characterized by excessive fat accumulation in the liver (steatosis), without any other evident causes of chronic liver diseases (viral, autoimmune, genetic, etc.), and with an alcohol consumption ≤20–30 g/day. On the contrary, AFLD is defined as the presence of steatosis and alcohol consumption >20–30 g/day. The most common phenotypic manifestations of primary NAFLD/NASH are overweight/obesity, visceral adiposity, type 2 diabetes, hypertriglyceridemia and hypertension. The prevalence of NAFLD in the general population in Western countries is estimated to be 25–30%. The prevalence and incidence of NASH and ASH are not known because of the impossibility of performing liver biopsy in the general population. Up to 90% of alcoholics have fatty liver, and 5–15% of these subjects will develop cirrhosis over 20 years. The risk of cirrhosis increases to 30–40% in those who continue to drink alcohol. About 10–35% of alcoholics exhibit changes on liver biopsy consistent with alcoholic hepatitis. Natural histories of NASH and ASH are not completely defined, even if patients with NASH have a reduced life expectancy due to liver-related death and cardiovascular diseases. The best treatment of AFLD/ASH is to stop drinking, and the most effective first-line therapeutic option for NAFLD/NASH is non-pharmacologic lifestyle interventions through a multidisciplinary approach including weight loss, dietary changes, physical exercise, and cognitive-behavior therapy.



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References

  1. Loria P, et al: Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease. A decalogue from the Italian Association for the Study of the Liver (AISF) Expert Committee. Dig Liver Dis 2010;42:272–282.
  2. Ratziu V, et al: A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol 2010;53:372–384.
  3. Baumeister SE, et al: Impact of fatty liver disease on health care utilization and costs in a general population: a 5-year observation. Gastroenterology 2008;134:85–94.
  4. Bellentani S, et al: Drinking habits as cofactors of risk for alcohol induced liver damage. The Dionysos Study Group. Gut 1997;41:845–850.
  5. Bellentani S, et al: Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 2000;132:112–117.
  6. Marchesini G, et al: Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001;50:1844–1850.
  7. Moucari R, et al: Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology 2008;134:416–423.
  8. Powell EE, et al: Steatosis is a cofactor in liver injury in hemochromatosis. Gastroenterology 2005;129:1937–1943.
  9. Naveau S, et al: Excess weight is a risk factor for alcoholic liver disease. Hepatology 1997;25:108–111.
  10. Powell EE, et al: Steatosis: co-factor in other liver diseases. Hepatology 2005;42:5–13.
  11. Corrao G, et al: Are the recent trends in liver cirrhosis mortality affected by the changes in alcohol consumption? Analysis of latency period in European countries. J Stud Alcohol 1997;58:486–494.
  12. Mendenhall CL: Anabolic steroid therapy as an adjunct to diet in alcoholic hepatic steatosis. Am J Dig Dis 1968;13:783–791.
  13. Leevy CM: Fatty liver: a study of 270 patients with biopsy proven fatty liver and review of the literature. Medicine (Baltimore) 1962;41:249–276.
  14. Sorensen TI, et al: Prospective evaluation of alcohol abuse and alcoholic liver injury in men as predictors of development of cirrhosis. Lancet 1984;2:241–244.
  15. Teli MR, et al: Determinants of progression to cirrhosis or fibrosis in pure alcoholic fatty liver. Lancet 1995;346:987–990.
  16. Bedogni G, et al: Prevalence of and risk factors for nonalcoholic fatty liver disease: The Dionysos Nutrition and Liver Study. Hepatology 2005;42:44–52.
  17. Zelber-Sagi S, et al: Prevalence of primary non-alcoholic fatty liver disease in a population-based study and its association with biochemical and anthropometric measures. Liver Int 2006;26:856–863.
  18. Fan JG, et al: Prevalence of and risk factors for fatty liver in a general population of Shanghai, China. J Hepatol 2005;43:508–514.
  19. Nomura H, et al: Prevalence of fatty liver in a general population of Okinawa, Japan. Jpn J Med 1988;27:142–149.
  20. Hilden M, et al: Liver histology in a ‘normal’ population – examinations of 503 consecutive fatal traffic casualties. Scand J Gastroenterol 1977;12:593–597.
  21. Ground KE, Liver pathology in aircrew. Aviat Space Environ Med 1982;53:14–18.
  22. Minervini MI, et al: Liver biopsy findings from healthy potential living liver donors: reasons for disqualification, silent diseases and correlation with liver injury tests. J Hepatol 2009;50:501–510.
  23. Nadalin S, et al: Preoperative donor liver biopsy for adult living donor liver transplantation: risks and benefits. Liver Transpl 2005;11:980–986.
  24. Ryan CK, et al: One hundred consecutive hepatic biopsies in the workup of living donors for right lobe liver transplantation. Liver Transpl 2002;8:1114–1122.
  25. Tran TT, et al: Living donor liver transplantation: histological abnormalities found on liver biopsies of apparently healthy potential donors. J Gastroenterol Hepatol 2006;21:381–383.
  26. Browning JD, et al: Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40:1387–1395.
  27. Weston SR, et al: Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease. Hepatology 2005;41:372–379.
  28. De Ledinghen V, et al: Diagnostic and predictive factors of significant liver fibrosis and minimal lesions in patients with persistent unexplained elevated transaminases. A prospective multicenter study. J Hepatol 2006;45:592–599.
  29. Soderberg C, et al: Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology 2010;51:595–602.

    External Resources

  30. Campos GM, et al: A clinical scoring system for predicting nonalcoholic steatohepatitis in morbidly obese patients. Hepatology 2008;47:1916–1923.
  31. Machado M, Marques-Vidal P, Cortez-Pinto H: Hepatic histology in obese patients undergoing bariatric surgery. J Hepatol 2006;45:600–606.
  32. Bedogni G, et al: Incidence and natural course of fatty liver in the general population: The Dionysos Study. Hepatology 2007;46:1387–1391.
  33. Hamaguchi M, et al: The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med 2005;143:722–728.
  34. Bruno S, et al: Incidence and risk factors for non-alcoholic steatohepatitis: prospective study of 5,408 women enrolled in Italian Tamoxifen Chemoprevention Trial. BMJ 2005;330:932.
  35. El-Hassan AY, et al: Fatty infiltration of the liver: analysis of prevalence, radiological and clinical features and influence on patient management. Br J Radiol 1992;65:774–778.
  36. Bacon BR, et al: Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology 1994;107:1103–1109.
  37. Powell EE, et al: The natural history of nonalcoholic steatohepatitis: a follow-up study of 42 patients for up to 21 years. Hepatology 1990;11:74–80.
  38. Frith J, et al: Non-alcoholic fatty liver disease in older people. Gerontology 2009;55:607–613.
  39. Schwimmer JB, et al: Heritability of nonalcoholic fatty liver disease. Gastroenterology 2009;136:1585–1592.
  40. Wagenknecht LE, et al: Correlates and heritability of nonalcoholic fatty liver disease in a minority cohort. Obesity (Silver Spring) 2009;17:1240–1246.
  41. Marchesini G, et al: Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 1999;107:450–455.
  42. Marchesini G, et al: Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003;37:917–923.
  43. Suzuki A, et al: Chronological development of elevated aminotransferases in a nonalcoholic population. Hepatology 2005;41:64–71.
  44. Hamaguchi M, et al: The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med 2005;143:722–728.
  45. Dam-Larsen S, et al: Long-term prognosis of fatty liver: risk of chronic liver disease and death. Gut 2004;53:750–755.
  46. Ekstedt M, et al: Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006;44:865–873.
  47. Gastaldelli A, et al: Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population. Hepatology 2009;49:1537–1544.
  48. Feldstein AE, et al: Free fatty acids promote hepatic lipotoxicity by stimulating TNF-α expression via a lysosomal pathway. Hepatology 2004;40:185–194.
  49. Day CP, James OF: Hepatic steatosis: innocent bystander or guilty party? Hepatology 1998;27:1463–1466.
  50. Pan M, et al: Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production. J Clin Invest 2004;113:1277–1287.
  51. Zou C, et al: Lack of Fas antagonism by Met in human fatty liver disease. Nat Med 2007;13:1078–1085.
  52. Ji C, Kaplowitz N: ER stress: can the liver cope? J Hepatol 2006;45:321–333.
  53. Marra F, et al: Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis. Trends Mol Med 2008;14:72–81.
  54. Lakshman MR: Some novel insights into the pathogenesis of alcoholic steatosis. Alcohol 2004;34:45–48.
  55. Thiele GM, Freeman TL, Klassen LW: Immunologic mechanisms of alcoholic liver injury. Semin Liver Dis 2004;24:273–287.
  56. Lieber CS, ALCOHOL: its metabolism and interaction with nutrients. Annu Rev Nutr 2000;20:395–430.
  57. Paradis V, et al: High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology 2001;34:738–744.
  58. Fehrenbach H, et al: Up-regulated expression of the receptor for advanced glycation end products in cultured rat hepatic stellate cells during transdifferentiation to myofibroblasts. Hepatology 2001;34:943–952.
  59. Marra F, Bertolani C: Adipokines in liver diseases. Hepatology 2009;50:957–969.
  60. Hui JM, et al: Beyond insulin resistance in NASH: TNF-α or adiponectin? Hepatology 2004;40:46–54.
  61. Kadowaki T, et al: Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006;116:1784–1792.
  62. Levitsky J, Mailliard ME: Diagnosis and therapy of alcoholic liver disease. Semin Liver Dis 2004;24:233–247.
  63. Hannuksela ML, et al: Biochemical markers of alcoholism. Clin Chem Lab Med 2007;45:953–961.
  64. Yersin B, et al: Screening for excessive alcohol drinking. Comparative value of carbohydrate-deficient transferring, γ-glutamyltransferase, and mean corpuscular volume. Arch Intern Med 1995;155:1907–1911.
  65. Conigrave KM, et al: CDT, GGT, and AST as markers of alcohol use: the WHO/ISBRA collaborative project. Alcohol Clin Exp Res 2002;26:332–339.
  66. Uchida T, et al: Alcoholic foamy degeneration – a pattern of acute alcoholic injury of the liver. Gastroenterology 1983;84:683–692.
  67. Nyblom H, et al: High AST/ALT ratio may indicate advanced alcoholic liver disease rather than heavy drinking. Alcohol Alcohol 2004;39:336–339.
  68. Bortolotti F, De Paoli G, Tagliaro F: Carbohydrate-deficient transferrin as a marker of alcohol abuse: a critical review of the literature 2001–2005. J Chromatogr B Analyt Technol Biomed Life Sci 2006;841:96–109.
  69. Bedogni G, et al: The fatty liver index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol 2006;6:33.
  70. Poynard T, et al: The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis. Comp Hepatol 2005;4:10.
  71. Kotronen A, et al: Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology 2009;137:865–872.
  72. Bedogni G, et al: A simple index of lipid overaccumulation is a good marker of liver steatosis. BMC Gastroenterol 2010;10:98.
  73. Zelber-Sagi S, et al: Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study. Hepatology 2008;48:1791–1798.
  74. Ratziu V, et al: Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease. BMC Gastroenterology 2006;6:6.
  75. Guha IN, et al: Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: validating the European Liver Fibrosis Panel and exploring simple markers. Hepatology 2008;47:455–460.
  76. Cales P, et al: Comparison of blood tests for liver fibrosis specific or not to NAFLD. J Hepatol 2009;50:165–173.
  77. Harrison SA, et al: Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut 2008;57:1441–1447.
  78. Angulo P, et al: The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007;45:846–854.
  79. Ratziu V, et al: Liver fibrosis in overweight patients. Gastroenterology 2000;118:1117–1123.
  80. Wahrenberg H, et al: Use of waist circumference to predict insulin resistance: retrospective study. BMJ 2005;330:1363–1364.
  81. Matthews DR, et al: Homeostasis model assessment: insulin resistance and β-cell function from plasma fasting glucose and insulin concentrations in man. Diabetologia 1985;28:412–419.
  82. Katz A, et al: Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000;85:2402–2410.
  83. Bugianesi E, McCullough AJ, Marchesini G: Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology 2005;42:987–1000.
  84. Mari A, et al: A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care 2001;24:539–548.
  85. McLaughlin T, et al: Is there a simple way to identify insulin-resistant individuals at increased risk of cardiovascular disease? Am J Cardiol 2005;96:399–404.
  86. Saadeh S, et al: The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002;123:745–750.
  87. Angulo P: Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221–1231.
  88. Mancini M, et al: Sonographic hepatic-renal ratio as indicator of hepatic steatosis: comparison with 1H-magnetic resonance spectroscopy. Metabolism 2009;58:1724–1730.
  89. D’Assignies G, et al: Noninvasive quantitation of human liver steatosis using magnetic resonance and bioassay methods. Eur Radiol 2009;19:2033–2040.
  90. McPherson S, et al: Magnetic resonance imaging and spectroscopy accurately estimate the severity of steatosis provided the stage of fibrosis is considered. J Hepatol 2009;51:389–397.
  91. Nobili V, et al: Accuracy and reproducibility of transient elastography for the diagnosis of fibrosis in pediatric nonalcoholic steatohepatitis. Hepatology 2008;48:442–448.
  92. Yoneda M, 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.
  93. Poynard T, et al: Concordance in a world without a gold standard: a new non-invasive methodology for improving accuracy of fibrosis markers. PLoS One 2008;3:e3857.
  94. Kim KM, et al: Diagnosis of hepatic steatosis and fibrosis by transient elastography in asymptomatic healthy individuals: a prospective study of living related potential liver donors. J Gastroenterol 2007;42:382–388.
  95. Roulot D, et al: Liver stiffness values in apparently healthy subjects: influence of gender and metabolic syndrome. J Hepatol 2008;48:606–613.
  96. Arena U, et al: Acute viral hepatitis increases liver stiffness values measured by transient elastography. Hepatology 2008;47:380–384.
  97. Millonig G, et al: Extrahepatic cholestasis increases liver stiffness (FibroScan) irrespective of fibrosis. Hepatology 2008;48:1718–1723.
  98. Lebray P, et al: Liver stiffness is an unreliable marker of liver fibrosis in patients with cardiac insufficiency. Hepatology 2008;48:2089.
  99. Ratziu V, et al: Can nonalcoholic steatohepatitis be diagnosed without liver biopsy? Biomarkers Med 2009;3:353–361.
  100. Poynard T, et al: Diagnostic value of biochemical markers (NashTest) for the prediction of non alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol 2006;6:34.
  101. Feldstein AE, et al: Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology 2009;50:1072–1078.
  102. Younossi ZM, et al: A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis. Obes Surg 2008;18:1430–1437.
  103. Mattaponi CA, et al: Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999;116:1413–1419.
  104. Brunt EM, et al: Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): a histologic marker of advanced NAFLD – clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network. Hepatology 2009;49:809–820.
  105. Brunt EM, Histopathology of non-alcoholic fatty liver disease. Clin Liver Dis 2009;13:533–544.
  106. Kleiner DE, et al: Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313–1321.
  107. Worner TM, Lieber CS: Perivenular fibrosis as precursor lesion of cirrhosis. JAMA 1985;254:627–630.
  108. Savolainen V, et al: Early perivenular fibrogenesis – precirrhotic lesions among moderate alcohol consumers and chronic alcoholics. J Hepatol 1995;23:524–531.
  109. Nakano M, Worner TM, Lieber CS: Perivenular fibrosis in alcoholic liver injury: ultrastructure and histologic progression. Gastroenterology 1982;83:777–785.
  110. MacSween RN, Scott AR: Hepatic cirrhosis: a clinico-pathological review of 520 cases. J Clin Pathol 1973;26:936–942.
  111. Schwimmer JB, et al: Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 2005;42:641–649.
  112. Abrams GA, et al: Portal fibrosis and hepatic steatosis in morbidly obese subjects: a spectrum of nonalcoholic fatty liver disease. Hepatology 2004;40:475–483.
  113. Dixon JB, Bhathal PS, O’Brien PE: Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 2001;121:91–100.
  114. Ratziu V, et al: Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005;128:1898–1906.
  115. Vuppalanchi R, et al: Effects of liver biopsy sample length and number of readings on sampling variability in nonalcoholic Fatty liver disease. Clin Gastroenterol Hepatol 2009;7:481–486.
  116. Bedossa P, Dargere D, Paradis V: Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology 2003;38:1449–1457.
  117. Sougioultzis S, et al: Alcoholic hepatitis: from pathogenesis to treatment. Curr Med Res Opin 2005;21:1337–1346.
  118. Younossi ZM, Review article: current management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2008;28:2–12.
  119. O’Shea RS, Dasarathy S, McCullough AJ: Alcoholic liver disease. Am J Gastroenterol 105:14–32; quiz 33.
  120. Stickel F, et al: Nutritional therapy in alcoholic liver disease. Aliment Pharmacol Ther 2003;18:357–373.
  121. Pessione F, et al: Five-year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking and abstinence. Liver Int 2003;23:45–53.
  122. Borowsky SA, Strome S, Lott E: Continued heavy drinking and survival in alcoholic cirrhotics. Gastroenterology 1981;80:1405–1409.
  123. Brunt PW, et al: Studies in alcoholic liver disease in Britain. I. Clinical and pathological patterns related to natural history. Gut 1974;15:52–58.
  124. Luca A, et al: Effects of ethanol consumption on hepatic hemodynamics in patients with alcoholic cirrhosis. Gastroenterology 1997;112:1284–1289.
  125. Kelly JP, et al: Alcohol consumption and the risk of major upper gastrointestinal bleeding. Am J Gastroenterol 1995;90:1058–1064.
  126. Halsted CH: Nutrition and alcoholic liver disease. Semin Liver Dis 2004;24:289–304.
  127. Lochs H, Plauth M: Liver cirrhosis: rationale and modalities for nutritional support–the European Society of Parenteral and Enteral Nutrition consensus and beyond. Curr Opin Clin Nutr Metab Care 1999;2:345–349.
  128. Neuschwander-Tetri BA: Lifestyle modification as the primary treatment of NASH. Clin Liver Dis 2009;13:649–665.
  129. Petersen KF, et al: 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.
  130. Tiikkainen M, et al: Effects of identical weight loss on body composition and features of insulin resistance in obese women with high and low liver fat content. Diabetes 2003;52:701–707.
  131. Palmer M, Schaffner F: Effect of weight reduction on hepatic abnormalities in overweight patients. Gastroenterology 1990;99:1408–1413.
  132. Suzuki A, et al: Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J Hepatol 2005;43:1060–1066.
  133. Harrison SA, et al: Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial. Hepatology 2009;49:80–86.
  134. Sacks FM, et al: Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009;360:859–873.
  135. Bellentani S, et al: Behavior therapy for nonalcoholic fatty liver disease: The need for a multidisciplinary approach. Hepatology 2008;47:746–754.
  136. Tetri LH, et al: Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent. Am J Physiol Gastrointest Liver Physiol 2008;295:G987–G995.
  137. Kechagias S, et al: Fast-food-based hyperalimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects. Gut 2008;57:649–654.
  138. Araya J, et al: Increase in long-chain polyunsaturated fatty acid n–6/n–3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease. Clin Sci (Lond) 2004;106:635–643.
  139. Ouyang X, et al: Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol 2008;48:993–999.
  140. Lee S, Gura KM, Puder M: Omega–3 fatty acids and liver disease. Hepatology 2007;45:841–845.
  141. Cortez-Pinto H, et al: How different is the dietary pattern in non-alcoholic steatohepatitis patients? Clin Nutr 2006;25:816–823.
  142. Zelber-Sagi S, et al: Long-term nutritional intake and the risk for non-alcoholic fatty liver disease: a population-based study. J Hepatol 2007;47:711–717.
  143. Levy JR, Clore JN, Stevens W: Dietary n–3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats. Hepatology 2004;39:608–616.
  144. Sekiya M, et al: Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology 2003;38:1529–1539.
  145. Capanni M, et al: Prolonged n–3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study. Aliment Pharmacol Ther 2006;23:1143–1151.
  146. Tanaka N, et al: Highly purified eicosapentaenoic acid treatment improves nonalcoholic steatohepatitis. J Clin Gastroenterol 2008;42:413–418.
  147. Krasnoff JB, et al: Health-related fitness and physical activity in patients with nonalcoholic fatty liver disease. Hepatology 2008;47:1158–1166.
  148. Newton JL, et al: Fatigue in non-alcoholic fatty liver disease is significant and associates with inactivity and excessive daytime sleepiness but not with liver disease severity or insulin resistance. Gut 2008;57:807–813.
  149. Church TS, et al: Association of cardiorespiratory fitness, body mass index, and waist circumference to nonalcoholic fatty liver disease. Gastroenterology 2006;130:2023–2030.
  150. Frith J, et al: Potential strategies to improve uptake of exercise interventions in non-alcoholic fatty liver disease. J Hepatol 2010;52:112–116.
  151. Perseghin G, et al: Habitual physical activity is associated with intrahepatic fat content in humans. Diabetes Care 2007;30:683–688.
  152. Mikines KJ, The influence of physical activity and inactivity on insulin action and secretion in man. Acta Physiol Scand Suppl 1992;609:1–43.
  153. Ibanez J, et al: Twice-weekly progressive resistance training decreases abdominal fat and improves insulin sensitivity in older men with type 2 diabetes. Diabetes Care 2005;28:662–667.
  154. Johnson NA, et al: Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology 2009;50:1105–1112.
  155. St George A, et al: Independent effects of physical activity in patients with nonalcoholic fatty liver disease. Hepatology 2009;50:68–76.
  156. Helmerhorst HJ, et al: Objectively measured sedentary time may predict insulin resistance independent of moderate- and vigorous-intensity physical activity. Diabetes 2009;58:1776–1779.
  157. Lieber CS: New concepts of the pathogenesis of alcoholic liver disease lead to novel treatments. Curr Gastroenterol Rep 2004;6:60–65.


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