Management of fatty liver disease with the metabolic syndrome

References

• Baumeister SE, Volzke H, Marschall P, et al. Impact of fatty liver disease on health care utilization and costs in a general population: a 5-year observation. Gastroenterology 2008;134(1):85-94
   PubMed Web of Science ®Google Scholar
• Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 2012;142(7):1592-609
   PubMed Web of Science ®Google Scholar
• Ratziu V, Bellentani S, Cortez-Pinto H, et al. A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol 2010;53(2):372-84
   PubMed Web of Science ®Google Scholar
• Gao X, Fan JG; Study Group of Liver and Metabolism, Chinese Society of Endocrinology. Diagnosis and management of non-alcoholic fatty liver disease and related metabolic disorders: consensus statement from the Study Group of Liver and Metabolism, Chinese Society of Endocrinology. J Diabetes 2013;5(4):406-15
   PubMed Web of Science ®Google Scholar
• Thun MJ, Peto R, Lopez AD, et al. Alcohol consumption and mortality among middle-aged and elderly U.S. adults. N Engl J Med 1997;337(24):1705-14
   PubMed Web of Science ®Google Scholar
• Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med 2011;43(8):617-49
   PubMed Web of Science ®Google Scholar
• Charlton MR, Burns JM, Pedersen RA, et al. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology 2011;141(4):1249-53
   PubMed Web of Science ®Google Scholar
• Tarantino G, Finelli C. What about non-alcoholic fatty liver disease as a new criterion to define metabolic syndrome? World J Gastroenterol 2013;19(22):3375-84
   PubMed Web of Science ®Google Scholar
• Mottillo S, Filion KB, Genest J, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol 2010;56(14):1113-32
   PubMed Web of Science ®Google Scholar
• Ducluzeau PH, Boursier J, Bertrais S, et al. MRI measurement of liver fat content predicts the metabolic syndrome. Diabetes Metab 2013;39(4):314-21
   PubMedGoogle Scholar
• Bellentani S, Tiribelli C. The spectrum of liver disease in the general population: lesson from the Dionysos study. J Hepatol 2001;35(4):531-7
   PubMedGoogle Scholar
• Wong VW, Wong GL, Choi PC, et al. Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut 2010;59(7):969-74
   PubMed Web of Science ®Google Scholar
• Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 2013;10(6):330-44
   PubMed Web of Science ®Google Scholar
• Ryysy L, Hakkinen AM, Goto T, et al. Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients. Diabetes 2000;49(5):749-58
   PubMedGoogle Scholar
• Targher G, Chonchol M, Bertolini L, et al. Increased risk of CKD among type 2 diabetics with nonalcoholic fatty liver disease. J Am Soc Nephrol 2008;19(8):1564-70
   PubMed Web of Science ®Google Scholar
• Adams LA, Harmsen S, St Sauver JL, et al. Nonalcoholic fatty liver disease increases risk of death among patients with diabetes: a community-based cohort study. Am J Gastroenterol 2010;105(7):1567-73
   PubMed Web of Science ®Google Scholar
• Margariti E, Deutsch M, Manolakopoulos S, Papatheodoridis GV. Nonalcoholic fatty liver disease may develop in individuals with normal body mass index. J Gastroenterol 2012;25(1):45-51
   Google Scholar
• Park YW, Zhu S, Palaniappan L, et al. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med 2003;163(4):427-36
   PubMedGoogle Scholar
• Messier V, Karelis AD, Robillard ME, et al. Metabolically healthy but obese individuals: relationship with hepatic enzymes. Metabolism 2010;59(1):20-4
   PubMedGoogle Scholar
• Tarantino G, Caputi A. JNKs, insulin resistance and inflammation: a possible link between NAFLD and coronary artery disease. World J Gastroenterol 2011;17(33):3785-94
   PubMed Web of Science ®Google Scholar
• Wang Y, Li YY, Nie YQ, et al. Association between metabolic syndrome and the development of non-alcoholic fatty liver disease. Exp Ther Med 2013;6(1):77-84
   PubMedGoogle Scholar
• Porepa L, Ray JG, Sanchez-Romeu P, Booth GL. Newly diagnosed diabetes mellitus as a risk factor for serious liver disease. CMAJ 2010;2(11):26-531
   Google Scholar
• Fraser A, Harris R, Sattar N, et al. Alanine aminotransferase, gamma-glutamyltransferase, and incident diabetes: the British Women's Heart and Health Study and meta-analysis. Diabetes Care 2009;32(4):741-50
   PubMedGoogle Scholar
• Yamada T, Fukatsu M, Suzuki S, et al. Fatty liver predicts impaired fasting glucose and type 2 diabetes mellitus in Japanese undergoing a health checkup. J Gastroenterol Hepatol 2010;25(2):352-6
   PubMedGoogle Scholar
• Sung KC, Kim SH. Interrelationship between fatty liver and insulin resistance in the development of type 2 diabetes. J Clin Endocrinol Metab 2011;96(4):1093-7
   PubMedGoogle Scholar
• Bae JC, Rhee EJ, Lee WY, et al. Combined effect of nonalcoholic fatty liver disease and impaired fasting glucose on the development of type 2 diabetes: a 4-year retrospective longitudinal study. Diabetes Care 2011;34(3):727-9
   PubMed Web of Science ®Google Scholar
• Cicero AF, D'Addato S, Reggi A, On Behalf Of The Brisighella Heart Study C. Gender difference in hepatic steatosis index and lipid accumulation product ability to predict incident metabolic syndrome in the historical cohort of the Brisighella Heart Study. Metab Syndr Relat Disord 2013;11(6):412-16
   PubMedGoogle Scholar
• Ekstedt M, Franzen LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006;44(4):865-73
   PubMed Web of Science ®Google Scholar
• Stepanova M, Younossi ZM. Independent association between nonalcoholic fatty liver disease and cardiovascular disease in the US population. Clin Gastroenterol Hepatol 2012;10(6):646-50
   PubMed Web of Science ®Google Scholar
• Targher G, Bertolini L, Rodella S, et al. Nonalcoholic fatty liver disease is independently associated with an increased incidence of cardiovascular events in type 2 diabetic patients. Diabetes Care 2007;30(8):2119-21
   PubMed Web of Science ®Google Scholar
• Assy N, Djibre A, Farah R, et al. Presence of coronary plaques in patients with nonalcoholic fatty liver disease. Radiology 2010;254(2):393-400
   PubMedGoogle Scholar
• Wong VW, Wong GL, Yip GW, et al. Coronary artery disease and cardiovascular outcomes in patients with non-alcoholic fatty liver disease. Gut 2011;60(12):1721-7
   PubMed Web of Science ®Google Scholar
• Colak Y, Senates E, Yesil A, et al. Assessment of endothelial function in patients with nonalcoholic fatty liver disease. Endocrine 2013;43(1):100-7
   PubMedGoogle Scholar
• Lee YJ, Shim JY, Moon BS, et al. The relationship between arterial stiffness and nonalcoholic fatty liver disease. Dig Dis Sci 2012;57(1):196-203
   PubMedGoogle Scholar
• Sookoian S, Pirola CJ. Non-alcoholic fatty liver disease is strongly associated with carotid atherosclerosis: a systematic review. J Hepatol 2008;49(4):600-7
   PubMed Web of Science ®Google Scholar
• Hallsworth K, Hollingsworth KG, Thoma C, et al. Cardiac structure and function are altered in adults with non-alcoholic fatty liver disease. J Hepatol 2013;58(4):757-62
   PubMedGoogle Scholar
• Rijzewijk LJ, Jonker JT, van der Meer RW, et al. Effects of hepatic triglyceride content on myocardial metabolism in type 2 diabetes. J Am Coll Cardiol 2010;56(3):225-33
   PubMedGoogle Scholar
• Cusi K, Chang Z, Harrison S, et al. Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with non-alcoholic fatty liver disease. J Hepatol 2014;60(1):167-74
   PubMed Web of Science ®Google Scholar
• Machado MV, Cortez-Pinto H. Non-invasive diagnosis of non-alcoholic fatty liver disease. A critical appraisal. J Hepatol 2013;58(5):1007-19
   PubMed Web of Science ®Google Scholar
• Bozzetto L, Prinster A, Annuzzi G, et al. Liver fat is reduced by an isoenergetic MUFA diet in a controlled randomized study in type 2 diabetic patients. Diabetes Care 2012;35(7):1429-35
   PubMed Web of Science ®Google Scholar
• Zelber-Sagi S, Lotan R, Shlomai A, et al. Predictors for incidence and remission of NAFLD in the general population during a seven-year prospective follow-up. J Hepatol 2012;56(5):1145-51
   PubMed Web of Science ®Google Scholar
• Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010;51(1):121-9
   PubMed Web of Science ®Google Scholar
• Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA. Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial. Hepatology 2009;49(1):80-6
   PubMed Web of Science ®Google Scholar
• Thoma C, Day CP, Trenell MI. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol 2012;56(1):255-66
   PubMed Web of Science ®Google Scholar
• Andersen T, Gluud C, Franzmann MB, Christoffersen P. Hepatic effects of dietary weight loss in morbidly obese subjects. J Hepatol 1991;12(2):224-9
   PubMed Web of Science ®Google Scholar
• Kwon OW, Jun DW, Lee SM, et al. Carbohydrate but not fat is associated with elevated aminotransferases. Aliment Pharmacol Ther 2012. [Epub ahead of print]
   Google Scholar
• Santos FL, Esteves SS, da Costa Pereira A, et al. Systematic review and meta-analysis of clinical trials of the effects of low carbohydrate diets on cardiovascular risk factors. Obes Rev 2012;13(11):1048-66
   PubMed Web of Science ®Google Scholar
• Sacks FM, Bray GA, Carey VJ, et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009;360(9):859-73
   PubMed Web of Science ®Google Scholar
• Kirk E, Reeds DN, Finck BN, et al. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology 2009;136(5):1552-60
   PubMed Web of Science ®Google Scholar
• Haufe S, Engeli S, Kast P, et al. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects. Hepatology 2011;53(5):1504-14
   PubMed Web of Science ®Google Scholar
• Westerbacka J, Lammi K, Hakkinen AM, et al. Dietary fat content modifies liver fat in overweight nondiabetic subjects. J Clin Endocrinol Metab 2005;90(5):2804-9
   PubMedGoogle Scholar
• Browning JD, Baker JA, Rogers T, et al. Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. Am J Clin Nutr 2011;93(5):1048-52
   PubMedGoogle Scholar
• Johnston RD, Stephenson MC, Crossland H, et al. No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. Gastroenterology 2013;5(5):16-1025; e1012
   Google Scholar
• Abid A, Taha O, Nseir W, et al. Soft drink consumption is associated with fatty liver disease independent of metabolic syndrome. J Hepatol 2009;51(5):918-24
   PubMed Web of Science ®Google Scholar
• 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(6):1961-71
   PubMed Web of Science ®Google Scholar
• Yasutake K, Nakamuta M, Shima Y, et al. Nutritional investigation of non-obese patients with non-alcoholic fatty liver disease: the significance of dietary cholesterol. Scand J Gastroenterol 2009;44(4):471-7
   PubMed Web of Science ®Google Scholar
• Caballero F, Fernandez A, De Lacy AM, et al. Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH. J Hepatol 2009;50(4):789-96
   PubMed Web of Science ®Google Scholar
• Ioannou GN, Morrow OB, Connole ML, Lee SP. Association between dietary nutrient composition and the incidence of cirrhosis or liver cancer in the United States population. Hepatology 2009;50(1):175-84
   PubMedGoogle Scholar
• Musso G, Gambino R, Michieli F, Cassader M. Dietary Habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 2003;37:909-15
   PubMed Web of Science ®Google Scholar
• Machado MV, Ravasco P, Jesus L, et al. Blood oxidative stress markers in non-alcoholic steatohepatitis and how it correlates with diet. Scand J Gastroenterol 2008;43(1):95-102
   PubMed Web of Science ®Google Scholar
• Cao J, Dai DL, Yao L, et al. Saturated fatty acid induction of endoplasmic reticulum stress and apoptosis in human liver cells via the PERK/ATF4/CHOP signaling pathway. Mol Cell Biochem 2011;364(1-2):115-29
   Google Scholar
• Ricchi M, Odoardi MR, Carulli L, et al. Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes. J Gastroenterol Hepatol 2009;24(5):830-40
   PubMed Web of Science ®Google Scholar
• Cortez-Pinto H, Jesus L, Barros H, et al. How different is the dietary pattern in non-alcoholic steatohepatitis patients? Clin Nutr 2006(25):816-23
   PubMedGoogle Scholar
• Toshimitsu K, Matsuura B, Ohkubo I, et al. Dietary habits and nutrient intake in non-alcoholic steatohepatitis. Nutrition 2007;23(1):46-52
   PubMedGoogle Scholar
• Sawada N, Inoue M, Iwasaki M, et al. Consumption of n-3 fatty acids and fish reduces risk of hepatocellular carcinoma. Gastroenterology 2012;142(7):1468-75
   PubMed Web of Science ®Google Scholar
• Parker HM, Johnson NA, Burdon CA, et al. Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 2012;56(4):944-51
   PubMed Web of Science ®Google Scholar
• Risk and Prevention Study Collaborative Group. Roncaglioni MC, Tombesi M, Avanzini F, et al. n-3 fatty acids in patients with multiple cardiovascular risk factors. N Engl J Med 2013;368(19):1800-8
   PubMed Web of Science ®Google Scholar
• Ryan MC, Itsiopoulos C, Thodis T, et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol 2013;59(1):138-43
   PubMed Web of Science ®Google Scholar
• Sun Q, Ma J, Campos H, et al. A prospective study of trans fatty acids in erythrocytes and risk of coronary heart disease. Circulation 2007;115(14):1858-65
   PubMed Web of Science ®Google Scholar
• Obara N, Fukushima K, Ueno Y, et al. Possible involvement and the mechanisms of excess trans-fatty acid consumption in severe NAFLD in mice. J Hepatol 2010;53(2):326-34
   PubMed Web of Science ®Google Scholar
• Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R, et al. Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): a population based study. J Hepatol 2007;47(5):711-17
   PubMed Web of Science ®Google Scholar
• Ricci G, Canducci E, Pasini V, et al. Nutrient intake in Italian obese patients: relationships with insulin resistance and markers of non-alcoholic fatty liver disease. Nutrition 2011;27(6):672-6
   PubMedGoogle Scholar
• Dunn W, Xu R, Schwimmer JB. Modest wine drinking and decreased prevalence of suspected nonalcoholic fatty liver disease. Hepatology 2008;47(6):1947-54
   PubMed Web of Science ®Google Scholar
• Dunn W, Sanyal AJ, Brunt EM, et al. Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD). J Hepatol 2012;57(2):384-91
   PubMed Web of Science ®Google Scholar
• Moriya A, Iwasaki Y, Ohguchi S, et al. Alcohol consumption appears to protect against non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2011;33(3):378-88
   PubMedGoogle Scholar
• Bellentani S, Saccoccio G, Masutti F, et al. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 2000;132(2):112-17
   PubMedGoogle Scholar
• Ruhl CE, Everhart JE. Joint effects of body weight and alcohol on elevated serum alanine aminotransferase in the United States population. Clin Gastroenterol Hepatol 2005;3(12):1260-8
   PubMed Web of Science ®Google Scholar
• Loomba R, Yang HI, Su J, et al. Synergism between obesity and alcohol in increasing the risk of hepatocellular carcinoma: a prospective cohort study. Am J Epidemiol 2013;177(4):333-42
   PubMed Web of Science ®Google Scholar
• Ascha MS, Hanouneh IA, Lopez R, et al. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 2010;51(6):1972-8
   PubMed Web of Science ®Google Scholar
• Howard AA, Arnsten JH, Gourevitch MN. Effect of alcohol consumption on diabetes mellitus: a systematic review. Ann Intern Med 2004;140(3):211-19
   PubMed Web of Science ®Google Scholar
• Shai I, Wainstein J, Harman-Boehm I, et al. Glycemic effects of moderate alcohol intake among patients with type 2 diabetes: a multicenter, randomized, clinical intervention trial. Diabetes Care 2007;30(12):3011-16
   PubMedGoogle Scholar
• Davies MJ, Baer DJ, Judd JT, et al. Effects of moderate alcohol intake on fasting insulin and glucose concentrations and insulin sensitivity in postmenopausal women: a randomized controlled trial. JAMA 2002;287(19):2559-62
   PubMed Web of Science ®Google Scholar
• Athyros VG, Liberopoulos EN, Mikhailidis DP, et al. Association of drinking pattern and alcohol beverage type with the prevalence of metabolic syndrome, diabetes, coronary heart disease, stroke, and peripheral arterial disease in a Mediterranean cohort. Angiology 2007;58(6):689-97
   PubMed Web of Science ®Google Scholar
• King DE, Mainous AG III, Geesey ME. Adopting moderate alcohol consumption in middle age: subsequent cardiovascular events. Am J Med 2008;121(3):201-6
   PubMed Web of Science ®Google Scholar
• Di Castelnuovo A, Costanzo S, Bagnardi V, et al. Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies. Arch Intern Med 2006;166(22):2437-45
   PubMed Web of Science ®Google Scholar
• Flensborg-Madsen T, Knop J, Mortensen EL, et al. Amount of alcohol consumption and risk of developing alcoholism in men and women. Alcohol Alcohol 2007;42(5):442-7
   PubMedGoogle Scholar
• Yesil A, Yilmaz Y. Review article: coffee consumption, the metabolic syndrome and non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2013;38(9):1038-44
   PubMedGoogle Scholar
• Hino A, Adachi H, Enomoto M, et al. Habitual coffee but not green tea consumption is inversely associated with metabolic syndrome: an epidemiological study in a general Japanese population. Diabetes Res Clin Pract 2007;76(3):383-9
   PubMed Web of Science ®Google Scholar
• Takami H, Nakamoto M, Uemura H, et al. Inverse correlation between coffee consumption and prevalence of metabolic syndrome: baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima, Japan. J Epidemiol 2013;23(1):12-20
   PubMed Web of Science ®Google Scholar
• Driessen MT, Koppes LL, Veldhuis L, et al. Coffee consumption is not related to the metabolic syndrome at the age of 36 years: the Amsterdam Growth and Health Longitudinal Study. Eur J Clin Nutr 2009;63(4):536-42
   PubMedGoogle Scholar
• Birerdinc A, Stepanova M, Pawloski L, Younossi ZM. Caffeine is protective in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2012;35(1):76-82
   PubMed Web of Science ®Google Scholar
• Molloy JW, Calcagno CJ, Williams CD, et al. Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis. Hepatology 2012;55(2):429-36
   PubMed Web of Science ®Google Scholar
• Pan XR, Li GW, Hu YH, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 1997;20(4):537-44
   PubMed Web of Science ®Google Scholar
• Sullivan S, Kirk EP, Mittendorfer B, et al. Randomized trial of exercise effect on intrahepatic triglyceride content and lipid kinetics in nonalcoholic fatty liver disease. Hepatology 2012;55(6):1738-45
   PubMed Web of Science ®Google Scholar
• Hallsworth K, Fattakhova G, Hollingsworth KG, et al. Resistance exercise reduces liver fat and its mediators in non-alcoholic fatty liver disease independent of weight loss. Gut 2011;60(9):1278-83
   PubMed Web of Science ®Google Scholar
• 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(4):1105-12
   PubMed Web of Science ®Google Scholar
• Tamura Y, Tanaka Y, Sato F, et al. Effects of diet and exercise on muscle and liver intracellular lipid contents and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 2005;90(6):3191-6
   PubMed Web of Science ®Google Scholar
• Gauthier MS, Couturier K, Latour JG, Lavoie JM. Concurrent exercise prevents high-fat-diet-induced macrovesicular hepatic steatosis. Eur J Appl Physiol 2003;94(6):2127-34
   Google Scholar
• Slentz CA, Bateman LA, Willis LH, et al. Effects of aerobic vs. resistance training on visceral and liver fat stores, liver enzymes, and insulin resistance by HOMA in overweight adults from STRRIDE AT/RT. Am J Physiol 2011;301(5):E1033-9
   PubMed Web of Science ®Google Scholar
• Bacchi E, Negri C, Targher G, et al. Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 randomized trial). Hepatology 2013;58(4):1287-95
   PubMed Web of Science ®Google Scholar
• Fenkci S, Sarsan A, Rota S, Ardic F. Effects of resistance or aerobic exercises on metabolic parameters in obese women who are not on a diet. Adv Ther 2006;23(3):404-13
   PubMedGoogle Scholar
• O'Donovan G, Kearney EM, Nevill AM, et al. The effects of 24 weeks of moderate- or high-intensity exercise on insulin resistance. Eur J Appl Physiol 2005;95(5-6):522-8
   PubMedGoogle Scholar
• Scaglioni F, Marino M, Ciccia S, et al. Short-term multidisciplinary non-pharmacological intervention is effective in reducing liver fat content assessed non-invasively in patients with nonalcoholic fatty liver disease (NAFLD). Clin Res Hepatol Gastroenterol 2013;37(4):353-8
   PubMedGoogle Scholar
• Younossi ZM, Reyes MJ, Mishra A, et al. Systematic review with meta-analysis: non-alcoholic steatohepatitis - a case for personalised treatment based on pathogenic targets. Aliment Pharmacol Ther 2014;39(1):3-14
   PubMed Web of Science ®Google Scholar
• Vongsuvanh R, George J, Qiao L, van der Poorten D. Visceral adiposity in gastrointestinal and hepatic carcinogenesis. Cancer Lett 2013;330(1):1-10
   PubMedGoogle Scholar
• 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(6):623-8
   PubMed Web of Science ®Google Scholar
• 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(5):639-44
   PubMed Web of Science ®Google Scholar
• Gloy VL, Briel M, Bhatt DL, et al. Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials. BMJ 2013;347:f5934
   PubMed Web of Science ®Google Scholar
• Ikramuddin S, Korner J, Lee WJ, et al. Roux-en-Y gastric bypass vs intensive medical management for the control of type 2 diabetes, hypertension, and hyperlipidemia: the Diabetes Surgery Study randomized clinical trial. JAMA 2013;309(21):2240-9
   PubMed Web of Science ®Google Scholar
• Mummadi RR, Kasturi KS, Chennareddygari S, Sood GK. Effect of bariatric surgery on nonalcoholic fatty liver disease: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2008;6(12):1396-402
   PubMed Web of Science ®Google Scholar
• Mathurin P, Hollebecque A, Arnalsteen L, et al. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology 2009;137(2):532-40
   PubMed Web of Science ®Google Scholar
• Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010;362(18):1675-85
   PubMed Web of Science ®Google Scholar
• Hoofnagle JH, Van Natta ML, Kleiner DE, et al. Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2013;38(2):134-43
   PubMed Web of Science ®Google Scholar
• Lavine JE, Schwimmer JB, Van Natta ML, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA 2011;305(16):1659-68
   PubMed Web of Science ®Google Scholar
• Musso G, Cassader M, Rosina F, Gambino R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia 2012;55(4):885-904
   PubMed Web of Science ®Google Scholar
• Miller ER III, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142(1):37-46
   PubMed Web of Science ®Google Scholar
• Klein EA, Thompson IM Jr, Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011;306(14):1549-56
   PubMed Web of Science ®Google Scholar
• Schurks M, Glynn RJ, Rist PM, et al. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ 2010;341:c5702
   PubMed Web of Science ®Google Scholar
• Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 2011;34(3):274-85
   PubMed Web of Science ®Google Scholar
• 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(22):2297-307
   PubMed Web of Science ®Google Scholar
• Aithal GP, Thomas JA, Kaye PV, et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology 2008;135(4):1176-84
   PubMed Web of Science ®Google Scholar
• Mahady SE, Webster AC, Walker S, et al. The role of thiazolidinediones in non-alcoholic steatohepatitis - a systematic review and meta analysis. J Hepatol 2011;55(6):1383-90
   PubMed Web of Science ®Google Scholar
• Lutchman G, Modi A, Kleiner DE, et al. The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology 2007;46(2):424-9
   PubMed Web of Science ®Google Scholar
• Lewis JD, Ferrara A, Peng T, et al. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care 2011;34(4):916-22
   PubMed Web of Science ®Google Scholar
• Kenny PR, Brady DE, Torres DM, et al. Exenatide in the treatment of diabetic patients with non-alcoholic steatohepatitis: a case series. Am J Gastroenterol 2010;105(12):2707-9
   PubMedGoogle Scholar
• Cuthbertson DJ, Irwin A, Gardner CJ, et al. Improved glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists. PLoS One 2012;7(12):e50117
   PubMed Web of Science ®Google Scholar
• Hyogo H, Tazuma S, Arihiro K, et al. Efficacy of atorvastatin for the treatment of nonalcoholic steatohepatitis with dyslipidemia. Metabolism 2008;57(12):1711-18
   PubMed Web of Science ®Google Scholar
• Hyogo H, Yamagishi S, Maeda S, et al. Atorvastatin improves disease activity of nonalcoholic steatohepatitis partly through its tumour necrosis factor-alpha-lowering property. Dig Liver Dis 2012;44(6):492-6
   PubMedGoogle Scholar
• Gomez-Dominguez E, Gisbert JP, Moreno-Monteagudo JA, et al. A pilot study of atorvastatin treatment in dyslipemid, non-alcoholic fatty liver patients. Aliment Pharmacol Ther 2006;23(11):1643-7
   PubMedGoogle Scholar
• Nelson A, Torres DM, Morgan AE, et al. A pilot study using simvastatin in the treatment of nonalcoholic steatohepatitis: a randomized placebo-controlled trial. J Clin Gastroenterol 2009;43(10):990-4
   PubMed Web of Science ®Google Scholar
• Athyros VG, Katsiki N, Karagiannis A, Mikhailidis DP. Are statins 'IDEAL' for non-alcoholic fatty liver disease? Curr Med Res Opin 2014;30(2):229-31
   PubMed Web of Science ®Google Scholar
• Singh S, Singh PP, Singh AG, et al. Statins are associated with a reduced risk of hepatocellular cancer: a systematic review and meta-analysis. Gastroenterology 2013;144(2):323-32
   PubMed Web of Science ®Google Scholar
• Pradelli D, Soranna D, Scotti L, et al. Statins and primary liver cancer: a meta-analysis of observational studies. Eur J Cancer Prev 2013;22(3):229-34
   PubMedGoogle Scholar
• Dale KM, Coleman CI, Henyan NN, et al. Statins and cancer risk: a meta-analysis. JAMA 2006;295(1):74-80
   PubMed Web of Science ®Google Scholar
• Cholesterol Treatment Trialists Collaboration. Emberson JR, Kearney PM, et al. Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy. PLoS One 2012;7(1):e29849
   PubMedGoogle Scholar
• Athyros VG, Mikhailidis DP, Didangelos TP, et al. Effect of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome: a randomised study. Curr Med Res Opin 2006;22(5):873-83
   PubMed Web of Science ®Google Scholar
• Fernandez-Miranda C, Perez-Carreras M, Colina F, et al. A pilot trial of fenofibrate for the treatment of non-alcoholic fatty liver disease. Dig Liver Dis 2008;40(3):200-5
   PubMedGoogle Scholar
• Merat S, Malekzadeh R, Sohrabi MR, et al. Probucol in the treatment of non-alcoholic steatohepatitis: a double-blind randomized controlled study. J Hepatol 2003;38(4):414-18
   PubMed Web of Science ®Google Scholar
• Ishitobi T, Hyogo H, Tokumo H, et al. Efficacy of probucol for the treatment of non-alcoholic steatohepatitis with dyslipidemia: an open-label pilot study. Hepatol Res 2013. [Epub ahead of print]
   PubMedGoogle Scholar
• Yoneda M, Fujita K, Nozaki Y, et al. Efficacy of ezetimibe for the treatment of non-alcoholic steatohepatitis: an open-label, pilot study. Hepatol Res 2010;40(6):566-73
   PubMed Web of Science ®Google Scholar
• Park H, Shima T, Yamaguchi K, et al. Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease. J Gastroenterol 2011;46(1):101-7
   PubMed Web of Science ®Google Scholar
• Yokohama S, Yoneda M, Haneda M, et al. Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology 2004;40(5):1222-5
   PubMed Web of Science ®Google Scholar
• Hirata T, Tomita K, Kawai T, et al. Effect of telmisartan or losartan for treatment of nonalcoholic fatty liver disease: fatty liver protection trial by telmisartan or losartan study (FANTASY). Int J Endocrinol 2013;2013:587140
   PubMedGoogle Scholar
• Ratziu V, de Ledinghen V, Oberti F, et al. A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis. J Hepatol 2011;54(5):1011-19
   PubMed Web of Science ®Google Scholar
• Balmer ML, Siegrist K, Zimmermann A, Dufour JF. Effects of ursodeoxycholic acid in combination with vitamin E on adipokines and apoptosis in patients with nonalcoholic steatohepatitis. Liver Int 2009;29(8):1184-8
   PubMedGoogle Scholar
• Gabbi C, Bertolotti M, Anzivino C, et al. Effects of bile duct ligation and cholic acid treatment on fatty liver in two rat models of non-alcoholic fatty liver disease. Dig Liver Dis 2012;44(12):1018-26
   PubMedGoogle Scholar
• Mudaliar S, Henry RR, Sanyal AJ, et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 2013;145(3):574-82; e571
   PubMed Web of Science ®Google Scholar
• Van Wagner LB, Koppe SW, Brunt EM, et al. Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial. Ann Hepatol 2011;10(3):277-86
   PubMed Web of Science ®Google Scholar
• Zein CO, Yerian LM, Gogate P, et al. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology 2011;54(5):1610-19
   PubMed Web of Science ®Google Scholar
• Loguercio C, De Simone T, Federico A, et al. Gut-liver axis: a new point of attack to treat chronic liver damage? Am J Gastroenterol 2002;97(8):2144-6
   PubMedGoogle Scholar
• Loguercio C, Federico A, Tuccillo C, et al. Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol 2005;39(6):540-3
   PubMed Web of Science ®Google Scholar
• Aller R, De Luis DA, Izaola O, et al. Effect of a probiotic on liver aminotransferases in nonalcoholic fatty liver disease patients: a double blind randomized clinical trial. Eur Rev Med Pharmacol Sci 2011;15(9):1090-5
   PubMed Web of Science ®Google Scholar
• Malaguarnera M, Vacante M, Antic T, et al. Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis. Dig Dis Sci 2012;57(2):545-53
   PubMed Web of Science ®Google Scholar
• Wong VW, Won GL, Chim AM, et al. Treatment of nonalcoholic steatohepatitis with probiotics. A proof-of-concept study. Ann Hepatol 2013;12(2):256-62
   PubMed Web of Science ®Google Scholar