Clinical approaches to non-alcoholic fatty liver disease

World Journal of Gastroenterology

Volumn 20, Issue 7, 2014, Pages 1712-1723

  Schwenger, Katherine J P ^a   Allard, Johane P ^b  

^a UNIVERSITY OF TORONTO   (Canada)

^b TORONTO GENERAL HOSPITAL   (Canada)

Author keywords

Cirrhosis; Diagnosis; Management; Non alcoholic fatty liver disease; Pathogenesis; Steatohepatitis; Steatosis; Treatment

Indexed keywords

ALANINE AMINOTRANSFERASE; ALPHA TOCOPHEROL; ASCORBIC ACID; ASPARTATE AMINOTRANSFERASE; FRUCTOSE OLIGOSACCHARIDE; GAMMA GLUTAMYLTRANSFERASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INSULIN; INTERLEUKIN 6; METFORMIN; OMEGA 3 FATTY ACID; PIOGLITAZONE; PLACEBO; PREBIOTIC AGENT; PROBIOTIC AGENT; ROSIGLITAZONE; TUMOR NECROSIS FACTOR ALPHA; URSODEOXYCHOLIC ACID; ANTIOXIDANT;

ARTICLE; BARIATRIC SURGERY; DIET THERAPY; DISEASE CLASSIFICATION; HUMAN; LIFESTYLE MODIFICATION; MEDICAL DECISION MAKING; META ANALYSIS (TOPIC); NONALCOHOLIC FATTY LIVER; NONHUMAN; PATHOGENESIS; PHYSICAL ACTIVITY; RANDOMIZED CONTROLLED TRIAL (TOPIC); WEIGHT REDUCTION; BIOPSY; CANCER STAGING; DISEASE COURSE; FATTY LIVER; INFLAMMATION; INSULIN RESISTANCE; LIFESTYLE; LIVER; METABOLIC SYNDROME X; METABOLISM; MORBID OBESITY; NON-ALCOHOLIC FATTY LIVER DISEASE; OXIDATIVE STRESS; PATHOLOGY; RISK FACTOR;

ANTIOXIDANTS; BARIATRIC SURGERY; BIOPSY; DISEASE PROGRESSION; FATTY LIVER; HUMANS; INFLAMMATION; INSULIN RESISTANCE; LIFE STYLE; LIVER; METABOLIC SYNDROME X; NEOPLASM STAGING; NON-ALCOHOLIC FATTY LIVER DISEASE; OBESITY, MORBID; OXIDATIVE STRESS; RISK FACTORS;

EID: 84894257853     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i7.1712     Document Type: Article

References (115)

1. Clark JM, Diehl AM. Hepatic steatosis and type 2 diabetes mellitus. Curr Diab Rep 2002; 2: 210-215 [PMID: 12643175]
2. 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 [PMID: 15895401 DOI: 10.1002/ hep.20734]
3. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40: 1387-1395 [PMID: 15565570 DOI: 10.1002/hep.20466]
4. 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: 274-285 [PMID: 21623852 DOI: 10.1111/j.1365-2036.2011.04724.x]
5. Machado M, Marques-Vidal P, Cortez-Pinto H. Hepatic histology in obese patients undergoing bariatric surgery. J Hepatol 2006; 45: 600-606 [PMID: 16899321 DOI: 10.1016/ j.jhep.2006.06.013]
6. Targher G, Bertolini L, Padovani R, Rodella S, Tessari R, Zenari L, Day C, Arcaro G. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007; 30: 1212-1218 [PMID: 17277038 DOI: 10.2337/dc06-2247]
7. Wieckowska A, Papouchado BG, Li Z, Lopez R, Zein NN, Feldstein AE. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol 2008; 103: 1372-1379 [PMID: 18510618 DOI: 10.1111/j.1572-0241.2007.01774.x]
8. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999; 116: 1413-1419 [PMID: 10348825]
9. van der Poorten D, Milner KL, Hui J, Hodge A, Trenell MI, Kench JG, London R, Peduto T, Chisholm DJ, George J. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology 2008; 48: 449-457 [PMID: 18627003 DOI: 10.1002/hep.22350]
10. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, Vanni E, Villanova N, Melchionda N, Rizzetto M. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003; 37: 917-923 [PMID: 12668987. DOI: 10.1053/jhep.2003.50161]
11. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221-1231 [PMID: 11961152 DOI: 10.1056/NEJMra011775]
12. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012; 55: 2005-2023 [PMID: 22488764 DOI: 10.1002/hep.25762]
13. Lewis JR, Mohanty SR. Nonalcoholic fatty liver disease: a review and update. Dig Dis Sci 2010; 55: 560-578 [PMID: 20101463. DOI: 10.1007/s10620-009-1081-0]
14. Yilmaz Y, Ulukaya E, Dolar E. A "biomarker biopsy" for the diagnosis of NASH: promises from CK-18 fragments. Obes Surg 2008; 18: 1507-1508; author reply 1509-1510 [PMID: 18679759. DOI: 10.1007/s11695-008-9639-z]
15. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005; 115: 1343-1351 [PMID: 15864352. DOI: 10.1172/jci200523621]
16. Dowman JK, Tomlinson JW, Newsome PN. Pathogenesis of non-alcoholic fatty liver disease. QJM 2010; 103: 71-83 [PMID: 19914930. DOI: 10.1093/qjmed/hcp158]
17. Bugianesi E, Marchesini G, Gentilcore E, Cua IH, Vanni E, Rizzetto M, George J. Fibrosis in genotype 3 chronic hepatitis C and nonalcoholic fatty liver disease: Role of insulin resistance and hepatic steatosis. Hepatology 2006; 44: 1648-1655 [PMID: 17133473 DOI: 10.1002/hep.21429]
18. Schreuder TC, Verwer BJ, van Nieuwkerk CM, Mulder CJ. Nonalcoholic fatty liver disease: an overview of current insights in pathogenesis, diagnosis and treatment. World J Gastroenterol 2008; 14: 2474-2486 [PMID: 18442193]
19. Petta S, Muratore C, Craxì A. Non-alcoholic fatty liver disease pathogenesis: the present and the future. Dig Liver Dis 2009; 41: 615-625 [PMID: 19223251 DOI: 10.1016/ j.dld.2009.01.004]
20. Jacobs RL, Lingrell S, Zhao Y, Francis GA, Vance DE. Hepatic CTP: phosphocholine cytidylyltransferase-alpha is a critical predictor of plasma high density lipoprotein and very low density lipoprotein. J Biol Chem 2008; 283: 2147-2155 [PMID: 18042552 DOI: 10.1074/jbc.M706628200]
21. Cortez-Pinto H, de Moura MC, Day CP. Non-alcoholic steatohepatitis: from cell biology to clinical practice. J Hepatol 2006; 44: 197-208 [PMID: 16274837 DOI: 10.1016/ j.jhep.2005.09.002]
22. Crespo J, Cayón A, Fernández-Gil P, Hernández-Guerra M, Mayorga M, Domínguez-Díez A, Fernández-Escalante JC, Pons-Romero F. Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology 2001; 34: 1158-1163 [PMID: 11732005. DOI: 10.1053/jhep.2001.29628]
23. Berg AH, Combs TP, Scherer PE. ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 2002; 13: 84-89 [PMID: 11854024]
24. Widhalm K, Ghods E. Nonalcoholic fatty liver disease: a challenge for pediatricians. Int J Obes (Lond) 2010; 34: 1451-1467 [PMID: 20838401 DOI: 10.1038/ijo.2010.185]
25. Jarrar MH, Baranova A, Collantes R, Ranard B, Stepanova M, Bennett C, Fang Y, Elariny H, Goodman Z, Chandhoke V, Younossi ZM. Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2008; 27: 412-421 [PMID: 18081738 DOI: 10.1111/j.1365-2036.2007.03586.x]
26. Lemoine M, Ratziu V, Kim M, Maachi M, Wendum D, Paye F, Bastard JP, Poupon R, Housset C, Capeau J, Serfaty L. Serum adipokine levels predictive of liver injury in nonalcoholic fatty liver disease. Liver Int 2009; 29: 1431-1438 [PMID: 19422483 DOI: 10.1111/j.1478-3231.2009.02022.x]
27. Mirza MS. Obesity, Visceral Fat, and NAFLD: Querying the Role of Adipokines in the Progression of Nonalcoholic Fatty Liver Disease. ISRN Gastroenterol 2011; 2011: 592404 [PMID: 21991518. DOI: 10.5402/2011/592404]
28. Marra F, Bertolani C. Adipokines in liver diseases. Hepatology 2009; 50: 957-969 [PMID: 19585655 DOI: 10.1002/ hep.23046]
29. Musso G, Gambino R, De Michieli F, Cassader M, Rizzetto M, Durazzo M, Fagà E, Silli B, Pagano G. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 2003; 37: 909-916 [PMID: 12668986 DOI: 10.1053/jhep.2003.50132]
30. Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R, Webb M, Blendis L, Halpern Z, Oren R. Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): a population based study. J Hepatol 2007; 47: 711-717 [PMID: 17850914. DOI: 10.1016/j.jhep.2007.06.020]
31. Sathiaraj E, Chutke M, Reddy MY, Pratap N, Rao PN, Reddy DN, Raghunath M. A case-control study on nutritional risk factors in non-alcoholic fatty liver disease in Indian population. Eur J Clin Nutr 2011; 65: 533-537 [PMID: 21346716. DOI: 10.1038/ejcn.2011.3]
32. Solga S, Alkhuraishe AR, Clark JM, Torbenson M, Greenwald A, Diehl AM, Magnuson T. Dietary composition and nonalcoholic fatty liver disease. Dig Dis Sci 2004; 49: 1578-1583 [PMID: 15573908]
33. Vos MB, Lavine JE. Dietary fructose in nonalcoholic fatty liver disease. Hepatology 2013; 57: 2525-2531 [PMID: 23390127. DOI: 10.1002/hep.26299]
34. Pollock NK, Bundy V, Kanto W, Davis CL, Bernard PJ, Zhu H, Gutin B, Dong Y. Greater fructose consumption is associated with cardiometabolic risk markers and visceral adiposity in adolescents. J Nutr 2012; 142: 251-257 [PMID: 22190023 DOI: 10.3945/jn.111.150219]
35. Lê KA, Faeh D, Stettler R, Ith M, Kreis R, Vermathen P, Boesch C, Ravussin E, Tappy L. A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans. Am J Clin Nutr 2006; 84: 1374-1379 [PMID: 17158419]
36. Mouzaki M, Comelli EM, Arendt BM, Bonengel J, Fung SK, Fischer SE, McGilvray ID, Allard JP. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 2013; 58: 120-127 [PMID: 23401313 DOI: 10.1002/hep.26319]
37. Spencer MD, Hamp TJ, Reid RW, Fischer LM, Zeisel SH, Fodor AA. Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency. Gastroenterology 2011; 140: 976-986 [PMID: 21129376 DOI: 10.1053/j.gastro.2010.11.049]
38. Raman M, Ahmed I, Gillevet PM, Probert CS, Ratcliffe NM, Smith S, Greenwood R, Sikaroodi M, Lam V, Crotty P, Bailey J, Myers RP, Rioux KP. Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2013; 11: 868-75. e1-3 [PMID: 23454028 DOI: 10.1016/j.cgh.2013.02.015]
39. Zhu L, Baker SS, Gill C, Liu W, Alkhouri R, Baker RD, Gill SR. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology 2013; 57: 601-609 [PMID: 23055155 DOI: 10.1002/hep.26093]
40. Dowman JK, Tomlinson JW, Newsome PN. Systematic review: the diagnosis and staging of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2011; 33: 525-540 [PMID: 21198708 DOI: 10.1111/ j.1365-2036.2010.04556.x]
41. Adams LA, Feldstein AE. Non-invasive diagnosis of nonalcoholic fatty liver and nonalcoholic steatohepatitis. J Dig Dis 2011; 12: 10-16 [PMID: 21091933 DOI: 10.1111/j.1751-2980.2010.00471. x]
42. Yan E, Durazo F, Tong M, Hong K. Nonalcoholic fatty liver disease: pathogenesis, identification, progression, and management. Nutr Rev 2007; 65: 376-384 [PMID: 17867371]
43. Pratt DS, Kaplan MM. Evaluation of abnormal liverenzyme results in asymptomatic patients. N Engl J Med 2000; 342: 1266-1271 [PMID: 10781624 DOI: 10.1056/ NEJM200004273421707]
44. Sorbi D, Boynton J, Lindor KD. The ratio of aspartate aminotransferase to alanine aminotransferase: potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease. Am J Gastroenterol 1999; 94: 1018-1022 [PMID: 10201476. DOI: 10.1111/j.1572-0241.1999.01006.x]
45. Adams LA, Angulo P, Lindor KD. Nonalcoholic fatty liver disease. CMAJ 2005; 172: 899-905 [PMID: 15795412 DOI: 10.1503/cmaj.045232]
46. Festi D, Schiumerini R, Marzi L, Di Biase AR, Mandolesi D, Montrone L, Scaioli E, Bonato G, Marchesini-Reggiani G, Colecchia A. Review article: the diagnosis of non-alcoholic fatty liver disease--availability and accuracy of noninvasive methods. Aliment Pharmacol Ther 2013; 37: 392-400 [PMID: 23278163 DOI: 10.1111/apt.12186]
47. Federico A, Trappoliere M, Loguercio C. Treatment of patients with non-alcoholic fatty liver disease: current views and perspectives. Dig Liver Dis 2006; 38: 789-801 [PMID: 16750661. DOI: 10.1016/j.dld.2006.04.009]
48. Pacifico L, Celestre M, Anania C, Paolantonio P, Chiesa C, Laghi A. MRI and ultrasound for hepatic fat quantification: relationships to clinical and metabolic characteristics of pediatric nonalcoholic fatty liver disease. Acta Paediatr 2007; 96: 542-547 [PMID: 17306008 DOI: 10.1111/ j.1651-2227.2007.00186.x]
49. Koehler EM, Schouten JN, Hansen BE, Hofman A, Stricker BH, Janssen HL. External validation of the fatty liver index for identifying nonalcoholic fatty liver disease in a population-based study. Clin Gastroenterol Hepatol 2013; 11: 1201-1204 [PMID: 23353640 DOI: 10.1016/j.cgh.2012.12.031]
50. Jiang ZY, Xu CY, Chang XX, Li WW, Sun LY, Yang XB, Yu LF. Fatty liver index correlates with non-alcoholic fatty liver disease, but not with newly diagnosed coronary artery atherosclerotic disease in Chinese patients. BMC Gastroenterol 2013; 13: 110 [PMID: 23834773 DOI: 10.1186/1471-230X-13-1 10]
51. Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, Tiribelli C. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol 2006; 6: 33 [PMID: 17081293 DOI: 10.1186/1471-230X-6-33]
52. Cortez-Pinto H, Camilo ME. Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH): diagnosis and clinical course. Best Pract Res Clin Gastroenterol 2004; 18: 1089-1104 [PMID: 15561640 DOI: 10.1016/ j.bpg.2004.06.021]
53. Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, Enders F, Saksena S, Burt AD, Bida JP, Lindor K, Sanderson SO, Lenzi M, Adams LA, Kench J, Therneau TM, Day CP. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007; 45: 846-854 [PMID: 17393509 DOI: 10.1002/ hep.21496]
54. Treeprasertsuk S, Björnsson E, Enders F, Suwanwalaikorn S, Lindor KD. NAFLD fibrosis score: a prognostic predictor for mortality and liver complications among NAFLD patients. World J Gastroenterol 2013; 19: 1219-1229 [PMID: 23482703 DOI: 10.3748/wjg.v19.i8.1219]
55. Qureshi K, Clements RH, Abrams GA. The utility of the "NAFLD fibrosis score" in morbidly obese subjects with NAFLD. Obes Surg 2008; 18: 264-270 [PMID: 18214632 DOI: 10.1007/s11695-007-9295-8]
56. Calès P, Lainé F, Boursier J, Deugnier Y, Moal V, Oberti F, Hunault G, Rousselet MC, Hubert I, Laafi J, Ducluzeaux PH, Lunel F. Comparison of blood tests for liver fibrosis specific or not to NAFLD. J Hepatol 2009; 50: 165-173 [PMID: 18977552. DOI: 10.1016/j.jhep.2008.07.035]
57. Wong VW, Vergniol J, Wong GL, Foucher J, Chan HL, Le Bail B, Choi PC, Kowo M, Chan AW, Merrouche W, Sung JJ, de Lédinghen V. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology 2010; 51: 454-462 [PMID: 20101745 DOI: 10.1002/hep.23312]
58. Wu SD, Wang JY, Li L. Staging of liver fibrosis in chronic hepatitis B patients with a composite predictive model: a comparative study. World J Gastroenterol 2010; 16: 501-507 [PMID: 20101779 DOI: 10.3748/wjg.v16.i4.501]
59. Yoneda M, Yoneda M, Mawatari H, Fujita K, Endo H, Iida H, Nozaki Y, Yonemitsu K, Higurashi T, Takahashi H, Kobayashi N, Kirikoshi H, Abe Y, Inamori M, Kubota K, Saito S, Tamano M, Hiraishi H, Maeyama S, Yamaguchi N, Togo S, Nakajima A. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD). Dig Liver Dis 2008; 40: 371-378 [PMID: 18083083. DOI: 10.1016/j.dld.2007.10.019]
60. Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, de Lédinghen V, Marcellin P, Dhumeaux D, Trinchet JC, Beaugrand M. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology 2005; 41: 48-54 [PMID: 15690481 DOI: 10.1002/hep.20506]
61. Yoneda M, Yoneda M, Fujita K, Inamori M, Tamano M, Hiriishi H, Nakajima A. Transient elastography in patients with non-alcoholic fatty liver disease (NAFLD). Gut 2007; 56: 1330-1331 [PMID: 17470477 DOI: 10.1136/gut.2007.126417]
62. Sandrin L, Tanter M, Gennisson JL, Catheline S, Fink M. Shear elasticity probe for soft tissues with 1-D transient elastography. IEEE Trans Ultrason Ferroelectr Freq Control 2002; 49: 436-446 [PMID: 11989699]
63. Myers RP, Pomier-Layrargues G, Kirsch R, Pollett A, Duarte-Rojo A, Wong D, Beaton M, Levstik M, Crotty P, Elkashab M. Feasibility and diagnostic performance of the FibroScan XL probe for liver stiffness measurement in overweight and obese patients. Hepatology 2012; 55: 199-208 [PMID: 21898479 DOI: 10.1002/hep.24624]
64. de Lédinghen V, Wong VW, Vergniol J, Wong GL, Foucher J, Chu SH, Le Bail B, Choi PC, Chermak F, Yiu KK, Merrouche W, Chan HL. Diagnosis of liver fibrosis and cirrhosis using liver stiffness measurement: comparison between M and XL probe of FibroScan®. J Hepatol 2012; 56: 833-839 [PMID: 22173167. DOI: 10.1016/j.jhep.2011.10.017]
65. Adams LA, Feldstein AE. Nonalcoholic steatohepatitis: risk factors and diagnosis. Expert Rev Gastroenterol Hepatol 2010; 4: 623-635 [PMID: 20932147 DOI: 10.1586/egh.10.56]
66. McCarthy EM, Rinella ME. The role of diet and nutrient composition in nonalcoholic Fatty liver disease. J Acad Nutr Diet 2012; 112: 401-409 [PMID: 22717200 DOI: 10.1016/ j.jada.2011.10.007]
67. Capristo E, Miele L, Forgione A, Vero V, Farnetti S, Mingrone G, Greco AV, Gasbarrini G, Grieco A. Nutritional aspects in patients with non-alcoholic steatohepatitis (NASH). Eur Rev Med Pharmacol Sci 2005; 9: 265-268 [PMID: 16231587]
68. Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR, Fava JL, Wing RR. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010; 51: 121-129 [PMID: 19827166 DOI: 10.1002/hep.23276]
69. 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: 255-266 [PMID: 21723839. DOI: 10.1016/j.jhep.2011.06.010]
70. Zelber-Sagi S, Ratziu V, Oren R. Nutrition and physical activity in NAFLD: an overview of the epidemiological evidence. World J Gastroenterol 2011; 17: 3377-3389 [PMID: 21876630. DOI: 10.3748/wjg.v17.i29.3377]
71. Lazo M, Solga SF, Horska A, Bonekamp S, Diehl AM, Brancati FL, Wagenknecht LE, Pi-Sunyer FX, Kahn SE, Clark JM. Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with type 2 diabetes. Diabetes Care 2010; 33: 2156-2163 [PMID: 20664019 DOI: 10.2337/dc10-0856]
72. Kantartzis K, Thamer C, Peter A, Machann J, Schick F, Schraml C, Königsrainer A, Königsrainer I, Kröber S, Niess A, Fritsche A, Häring HU, Stefan N. High cardiorespiratory fitness is an independent predictor of the reduction in liver fat during a lifestyle intervention in non-alcoholic fatty liver disease. Gut 2009; 58: 1281-1288 [PMID: 19074179 DOI: 10.1136/gut.2008.151977]
73. St George A, Bauman A, Johnston A, Farrell G, Chey T, George J. Effect of a lifestyle intervention in patients with abnormal liver enzymes and metabolic risk factors. J Gastroenterol Hepatol 2009; 24: 399-407 [PMID: 19067776 DOI: 10.1111/j.1440-1746.2008.05694.x]
74. Hallsworth K, Fattakhova G, Hollingsworth KG, Thoma C, Moore S, Taylor R, Day CP, Trenell MI. Resistance exercise reduces liver fat and its mediators in non-alcoholic fatty liver disease independent of weight loss. Gut 2011; 60: 1278-1283 [PMID: 21708823 DOI: 10.1136/gut.2011.242073]
75. Attar BM, Van Thiel DH. Current concepts and management approaches in nonalcoholic fatty liver disease. ScientificWorldJournal 2013; 2013: 481893 [PMID: 23576902 DOI: 10.1155/2013/481893]
76. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001; 108: 1167-1174 [PMID: 11602624 DOI: 10.1172/JCI13505]
77. Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE. Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med 1995; 333: 550-554 [PMID: 7623903. DOI: 10.1056/NEJM199508313330903]
78. Mazza A, Fruci B, Garinis GA, Giuliano S, Malaguarnera R, Belfiore A. The role of metformin in the management of NAFLD. Exp Diabetes Res 2012; 2012: 716404 [PMID: 22194737. DOI: 10.1155/2012/716404]
79. Nair S, Diehl AM, Wiseman M, Farr GH, Perrillo RP. Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther 2004; 20: 23-28 [PMID: 15225167 DOI: 10.1111/j.1365-2036.2004.02025.x]
80. Nobili V, Manco M, Ciampalini P, Alisi A, Devito R, Bugianesi E, Marcellini M, Marchesini G. Metformin use in children with nonalcoholic fatty liver disease: an open-label, 24-month, observational pilot study. Clin Ther 2008; 30: 1168-1176 [PMID: 18640473. DOI: 10.1016/j.clinthera.2008.06.012]
81. Haukeland JW, Konopski Z, Eggesbø HB, von Volkmann HL, Raschpichler G, Bjøro K, Haaland T, Løberg EM, Birkeland K. Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol 2009; 44: 853-860 [PMID: 19811343 DOI: 10.1080/0036552090 2845268]
82. Oh MK, Winn J, Poordad F. Review article: diagnosis and treatment of non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2008; 28: 503-522 [PMID: 18532991 DOI: 10.1111/ j.1365-2036.2008.03752.x]
83. Van Wagner LB, Rinella ME. The role of insulin-sensitizing agents in the treatment of nonalcoholic steatohepatitis. Therap Adv Gastroenterol 2011; 4: 249-263 [PMID: 21765869 DOI: 10.1177/1756283X11403809]
84. Caldwell SH, Argo CK, Al-Osaimi AM. Therapy of NAFLD: insulin sensitizing agents. J Clin Gastroenterol 2006; 40 Suppl 1: S61-S66 [PMID: 16540770]
85. Ratziu V, Giral P, Jacqueminet S, Charlotte F, Hartemann-Heurtier A, Serfaty L, Podevin P, Lacorte JM, Bernhardt C, Bruckert E, Grimaldi A, Poynard T. Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology 2008; 135: 100-110 [PMID: 18503774 DOI: 10.1053/j.gastro.2008.03.078]
86. Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, Balas B, Gastaldelli A, Tio F, Pulcini J, Berria R, Ma JZ, Dwivedi S, Havranek R, Fincke C, DeFronzo R, Bannayan GA, Schenker S, Cusi K. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355: 2297-2307 [PMID: 17135584 DOI: 10.1056/NEJMoa060326]
87. Lutchman G, Modi A, Kleiner DE, Promrat K, Heller T, Ghany M, Borg B, Loomba R, Liang TJ, Premkumar A, Hoofnagle JH. The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology 2007; 46: 424-429 [PMID: 17559148 DOI: 10.1002/hep.21661]
88. Aithal GP, Thomas JA, Kaye PV, Lawson A, Ryder SD, Spendlove I, Austin AS, Freeman JG, Morgan L, Webber J. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology 2008; 135: 1176-1184 [PMID: 18718471 DOI: 10.1053/j.gastro.2008.06.047]
89. Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010; 362: 1675-1685 [PMID: 20427778 DOI: 10.1056/NEJMoa0907929]
90. 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 [PMID: 14638353 DOI: 10.1111/ j.1572-0241.2003.08699.x]
91. Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005; 142: 37-46 [PMID: 15537682]
92. Klein EA, Thompson IM, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, Minasian LM, Ford LG, Parnes HL, Gaziano JM, Karp DD, Lieber MM, Walther PJ, Klotz L, Parsons JK, Chin JL, Darke AK, Lippman SM, Goodman GE, Meyskens FL, Baker LH. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011; 306: 1549-1556 [PMID: 21990298 DOI: 10.1001/jama.2011.1437]
93. Lindor KD, Kowdley KV, Heathcote EJ, Harrison ME, Jorgensen R, Angulo P, Lymp JF, Burgart L, Colin P. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 2004; 39: 770-778 [PMID: 14999696 DOI: 10.1002/hep.20092]
94. Santos VN, Lanzoni VP, Szejnfeld J, Shigueoka D, Parise ER. A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid. Braz J Med Biol Res 2003; 36: 723-729 [PMID: 12792701]
95. Masterton GS, Plevris JN, Hayes PC. Review article: omega-3 fatty acids-a promising novel therapy for non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2010; 31: 679-692 [PMID: 20415840 DOI: 10.1111/j.1365-2036.2010.04230.x]
96. Capanni M, Calella F, Biagini MR, Genise S, Raimondi L, Bedogni G, Svegliati-Baroni G, Sofi F, Milani S, Abbate R, Surrenti C, Casini A. 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 [PMID: 16611275 DOI: 10.1111/j.1365-2036.2006.02885.x]
97. Chatrath H, Vuppalanchi R, Chalasani N. Dyslipidemia in patients with nonalcoholic fatty liver disease. Semin Liver Dis 2012; 32: 22-29 [PMID: 22418885 DOI: 10.1055/ s-0032-1306423]
98. Athyros VG, Mikhailidis DP, Papageorgiou AA, Symeonidis AN, Pehlivanidis AN, Bouloukos VI, Elisaf M. The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study. J Clin Pathol 2004; 57: 728-734 [PMID: 15220366 DOI: 10.1136/jcp.2003.012989]
99. Maroni L, Guasti L, Castiglioni L, Marino F, Contini S, Macchi V, De Leo A, Gaudio G, Tozzi M, Grandi AM, Cosentino M, Venco A. Lipid targets during statin treatment in dyslipidemic patients affected by nonalcoholic fatty liver disease. Am J Med Sci 2011; 342: 383-387 [PMID: 21629037 DOI: 10.1097/MAJ.0b013e318213e526]
100. Ekstedt M, Franzén LE, Mathiesen UL, Holmqvist M, Bodemar G, Kechagias S. Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes: a histopathological follow-up study. J Hepatol 2007; 47: 135-141 [PMID: 17400325. DOI: 10.1016/j.jhep.2007.02.013]
101. Tandra S, Vuppalanchi R. Use of statins in patients with liver disease. Curr Treat Options Cardiovasc Med 2009; 11: 272-278 [PMID: 19627660]
102. Iacono A, Raso GM, Canani RB, Calignano A, Meli R. Probiotics as an emerging therapeutic strategy to treat NAFLD: focus on molecular and biochemical mechanisms. J Nutr Biochem 2011; 22: 699-711 [PMID: 21292470 DOI: 10.1016/ j.jnutbio.2010.10.002]
103. Parnell JA, Raman M, Rioux KP, Reimer RA. The potential role of prebiotic fibre for treatment and management of nonalcoholic fatty liver disease and associated obesity and insulin resistance. Liver Int 2012; 32: 701-711 [PMID: 22221818 DOI: 10.1111/j.1478-3231.2011.02730.x]
104. Daubioul CA, Horsmans Y, Lambert P, Danse E, Delzenne NM. Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis: results of a pilot study. Eur J Clin Nutr 2005; 59: 723-726 [PMID: 15770222. DOI: 10.1038/sj.ejcn.1602127]
105. Li Z, Yang S, Lin H, Huang J, Watkins PA, Moser AB, Desimone C, Song XY, Diehl AM. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology 2003; 37: 343-350 [PMID: 12540784. DOI: 10.1053/jhep.2003.50048]
106. Loguercio C, Federico A, Tuccillo C, Terracciano F, D'Auria MV, De Simone C, Del Vecchio Blanco C. Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol 2005; 39: 540-543 [PMID: 15942443]
107. Solga SF, Buckley G, Clark JM, Horska A, Diehl AM. The effect of a probiotic on hepatic steatosis. J Clin Gastroenterol 2008; 42: 1117-1119 [PMID: 18936646 DOI: 10.1097/ MCG.0b013e31816d920c]
108. Aller R, De Luis DA, Izaola O, Conde R, Gonzalez Sagrado M, Primo D, De La Fuente B, Gonzalez J. 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: 1090-1095 [PMID: 22013734]
109. Bellentani S, Saccoccio G, Masutti F, Crocè LS, Brandi G, Sasso F, Cristanini G, Tiribelli C. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 2000; 132: 112-117 [PMID: 10644271]
110. Cotrim HP, Daltro C. Liver: Does bariatric surgery reduce the severity of NAFLD? Nat Rev Gastroenterol Hepatol 2010; 7: 11-13 [PMID: 20051969 DOI: 10.1038/nrgastro.2009.215]
111. NIH conference. Gastrointestinal surgery for severe obesity. Consensus Development Conference Panel. Ann Intern Med 1991; 115: 956-961 [PMID: 1952493]
112. Baker MK, Byrne TK, Feldmann ME. Surgical treatment of obesity. Prim Care 2009; 36: 417-427 [PMID: 19501252 DOI: 10.1016/j.pop.2009.01.001]
113. Moschen AR, Molnar C, Wolf AM, Weiss H, Graziadei I, Kaser S, Ebenbichler CF, Stadlmann S, Moser PL, Tilg H. Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression. J Hepatol 2009; 51: 765-777 [PMID: 19664840. DOI: 10.1016/j.jhep.2009.06.016]
114. Furuya CK, de Oliveira CP, de Mello ES, Faintuch J, Raskovski A, Matsuda M, Vezozzo DC, Halpern A, Garrido AB, Alves VA, Carrilho FJ. Effects of bariatric surgery on nonalcoholic fatty liver disease: preliminary findings after 2 years. J Gastroenterol Hepatol 2007; 22: 510-514 [PMID: 17376042 DOI: 10.1111/j.1440-1746.2007.04833.x]
115. Chavez-Tapia NC, Tellez-Avila FI, Barrientos-Gutierrez T, Mendez-Sanchez N, Lizardi-Cervera J, Uribe M. Bariatric surgery for non-alcoholic steatohepatitis in obese patients. Cochrane Database Syst Rev 2010; (1): CD007340 [PMID: 20091629. DOI: 10.1002/14651858.CD007340.pub2]