Management of nonalcoholic fatty liver disease: An evidence-based clinical practice review

World Journal of Gastroenterology

Volumn 20, Issue 34, 2014, Pages 12182-12201

  Arab, Juan P ^a   Candia, Roberto ^a   Zapata, Rodrigo ^b,c   Muñoz, Cristián ^d   Arancibia, Juan P ^e   Poniachik, Jaime ^e   Soza, Alejandro ^a   Fuster, Francisco ^f   Brahm, Javier ^e,g   Sanhueza, Edgar ^c   Contreras, Jorge ^c   Cuellar, M Carolina ^a   Arrese, Marco ^a   Riquelme, Arnoldo ^a  

^a PONTIFICIA UNIVERSIDAD CATÓLICA DE CHILE   (Chile)

^b UNIVERSITY OF CHILE   (Chile)

^c UNIVERSIDAD DEL DESARROLLO   (Chile)

^d HOSPITAL DEL SALVADOR   (Chile)

^e HOSPITAL CLÍNICO UNIVERSIDAD DE CHILE   (Chile)

^f Unidad de Cuidados Intensivos   (Chile)

^g CLÍNICA LAS CONDES   (Chile)

Author keywords

Consensus; Evidence based medicine; Nonalcoholic fatty liver disease; Steatosis; Treatment

Indexed keywords

ALPHA TOCOPHEROL; PIOGLITAZONE;

CLINICAL PRACTICE; CONSENSUS; DELPHI STUDY; DIET; EVIDENCE BASED PRACTICE; EXERCISE; HUMAN; LIFESTYLE MODIFICATION; LIVER BIOPSY; NONALCOHOLIC FATTY LIVER; REVIEW; UNITED STATES; BIOPSY; CHILE; EVIDENCE BASED MEDICINE; HEALTH CARE SURVEY; NON-ALCOHOLIC FATTY LIVER DISEASE; PREDICTIVE VALUE; QUESTIONNAIRE; RISK ASSESSMENT; RISK FACTOR; TREATMENT OUTCOME;

BIOPSY; CHILE; CONSENSUS; DELPHI TECHNIQUE; EVIDENCE-BASED MEDICINE; HEALTH CARE SURVEYS; HUMANS; NON-ALCOHOLIC FATTY LIVER DISEASE; PREDICTIVE VALUE OF TESTS; QUESTIONNAIRES; RISK ASSESSMENT; RISK FACTORS; TREATMENT OUTCOME;

EID: 84909595165     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i34.12182     Document Type: Review

References (223)

1. Angulo P, Lindor KD. Non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2002; 17 Suppl: S186-S190 [PMID: 12000605]
2. Cheung O, Sanyal AJ. Recent advances in nonalcoholic fatty liver disease. Curr Opin Gastroenterol 2009; 25: 230-237 [PMID: 19396962]
3. 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]
4. Méndez-Sánchez N, Arrese M, Zamora-Valdés D, Uribe M. Current concepts in the pathogenesis of nonalcoholic fatty liver disease. Liver Int 2007; 27: 423-433 [PMID: 17403181]
5. 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]
6. Younossi ZM. Review article: current management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2008; 28: 2-12 [PMID: 18410557 DOI: 10.1111/j.1365-2036.2008.03710.x]
7. Riquelme A, Arrese M, Soza A, Morales A, Baudrand R, Pérez-Ayuso RM, González R, Alvarez M, Hernández V, García-Zattera MJ, Otarola F, Medina B, Rigotti A, Miquel JF, Marshall G, Nervi F. Non-alcoholic fatty liver disease and its association with obesity, insulin resistance and increased serum levels of C-reactive protein in Hispanics. Liver Int 2009; 29: 82-88 [PMID: 18647235 DOI: 10.1111/j.1478-3231.2008.01823.x]
8. Argo CK, Northup PG, Al-Osaimi AM, Caldwell SH. Systematic review of risk factors for fibrosis progression in nonalcoholic steatohepatitis. J Hepatol 2009; 51: 371-379 [PMID: 19501928]
9. Bellentani S, Marino M. Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD). Ann Hepatol 2009; 8 Suppl 1: S4-S8 [PMID: 19381118]
10. Caldwell S, Argo C. The natural history of non-alcoholic fatty liver disease. Dig Dis 2010; 28: 162-168 [PMID: 20460906 DOI: 10.1159/000282081]
11. Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology 2010; 51: 1820-1832 [PMID: 20432259 DOI: 10.1002/hep.23594]
12. Méndez-Sánchez N, Arrese M, Zamora-Valdés D, Uribe M. Treating nonalcoholic fatty liver disease. Liver Int 2007; 27: 1157-1165 [PMID: 17919226 DOI: 10.1111/j.1478-3231.2007.01567.x]
13. Vuppalanchi R, Chalasani N. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management. Hepatology 2009; 49: 306-317 [PMID: 19065650 DOI: 10.1002/hep.22603]
14. Arab JP, Ramírez C, Arrese M. Early warning of liver disease in diabetics. Ann Hepatol 2010; 9: 307-309 [PMID: 20720278]
15. Porepa L, Ray JG, Sanchez-Romeu P, Booth GL. Newly diagnosed diabetes mellitus as a risk factor for serious liver disease. CMAJ 2010; 182: E526-E531 [PMID: 20566726 DOI: 10.1503/cmaj.092144]
16. Adams LA, Angulo P. Recent concepts in non-alcoholic fatty liver disease. Diabet Med 2005; 22: 1129-1133 [PMID: 16108837 DOI: 10.1111/j.1464-5491.2005.01748.x]
17. Fan JG, Farrell GC. Epidemiology of non-alcoholic fatty liver disease in China. J Hepatol 2009; 50: 204-210 [PMID: 19014878 DOI: 10.1016/j.jhep.2008.10.010]
18. Rector RS, Thyfault JP, Wei Y, Ibdah JA. Non-alcoholic fatty liver disease and the metabolic syndrome: an update. World J Gastroenterol 2008; 14: 185-192 [PMID: 18186553]
19. Trauner M, Arrese M, Wagner M. Fatty liver and lipotoxicity. Biochim Biophys Acta 2010; 1801: 299-310 [PMID: 19857603 DOI: 10.1016/j.bbalip.2009.10.007]
20. Schwimmer JB, Celedon MA, Lavine JE, Salem R, Campbell N, Schork NJ, Shiehmorteza M, Yokoo T, Chavez A, Middleton MS, Sirlin CB. Heritability of nonalcoholic fatty liver disease. Gastroenterology 2009; 136: 1585-1592 [PMID: 19208353 DOI: 10.1053/j.gastro.2009.01.050]
21. Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005; 129: 113-121 [PMID: 16012941]
22. Angulo P. Long-term mortality in nonalcoholic fatty liver disease: is liver histology of any prognostic significance? Hepatology 2010; 51: 373-375 [PMID: 20101746 DOI: 10.1002/hep.23521]
23. Edens MA, Kuipers F, Stolk RP. Non-alcoholic fatty liver disease is associated with cardiovascular disease risk markers. Obes Rev 2009; 10: 412-419 [PMID: 19413701 DOI: 10.1111/j.1467-789X.2009.00594.x]
24. Zelber-Sagi S, Lotan R, Shibolet O, Webb M, Buch A, Nitzan-Kaluski D, Halpern Z, Santo E, Oren R. Non-alcoholic fatty liver disease independently predicts prediabetes during a 7-year prospective follow-up. Liver Int 2013; 33: 1406-1412 [PMID: 23656177 DOI: 10.1111/liv.12200]
25. Harris RP, Helfand M, Woolf SH, Lohr KN, Mulrow CD, Teutsch SM, Atkins D. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med 2001; 20: 21-35 [PMID: 11306229]
26. Sawaya GF, Guirguis-Blake J, LeFevre M, Harris R, Petitti D. Update on the methods of the U.S. Preventive Services Task Force: estimating certainty and magnitude of net benefit. Ann Intern Med 2007; 147: 871-875 [PMID: 18087058]
27. American Gastroenterological Association Medical Position Statement: guidelines for the use of enteral nutrition. Gastroenterology 1995; 108: 1280-1281 [PMID: 7698595]
28. Hayward RS, Wilson MC, Tunis SR, Bass EB, Guyatt G. Users' guides to the medical literature. VIII. How to use clinical practice guidelines. A. Are the recommendations valid? The Evidence-Based Medicine Working Group. JAMA 1995; 274: 570-574 [PMID: 7629987]
29. Letelier LM, Moore P. [Evidence based medicine: a view after a decade]. Rev Med Chil 2003; 131: 939-946 [PMID: 14558251]
30. Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA 1993; 270: 2598-2601 [PMID: 8230645]
31. Hasson F, Keeney S, McKenna H. Research guidelines for the Delphi survey technique. J Adv Nurs 2000; 32: 1008-1015 [PMID: 11095242]
32. 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]
33. Chen SM, Liu CY, Li SR, Huang HT, Tsai CY, Jou HJ. Effects of therapeutic lifestyle program on ultrasound-diagnosed nonalcoholic fatty liver disease. J Chin Med Assoc 2008; 71: 551-558 [PMID: 19015052 DOI: 10.1016/S1726-4901(08)70168-0]
34. Wang CL, Liang L, Fu JF, Zou CC, Hong F, Xue JZ, Lu JR, Wu XM. Effect of lifestyle intervention on non-alcoholic fatty liver disease in Chinese obese children. World J Gastroenterol 2008; 14: 1598-1602 [PMID: 18330955]
35. Sreenivasa Baba C, Alexander G, Kalyani B, Pandey R, Rastogi S, Pandey A, Choudhuri G. Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis. J Gastroenterol Hepatol 2006; 21: 191-198 [PMID: 16706832 DOI: 10.1111/j.1440-1746.2005.04233.x]
36. Ueno T, Sugawara H, Sujaku K, Hashimoto O, Tsuji R, Tamaki S, Torimura T, Inuzuka S, Sata M, Tanikawa K. Therapeutic effects of restricted diet and exercise in obese patients with fatty liver. J Hepatol 1997; 27: 103-107 [PMID: 9252081]
37. Satapathy SK, Sanyal AJ. Novel treatment modalities for nonalcoholic steatohepatitis. Trends Endocrinol Metab 2010; 21: 668-675 [PMID: 20880717 DOI: 10.1016/j.tem.2010.08.003]
38. Orchard TJ, Temprosa M, Goldberg R, Haffner S, Ratner R, Marcovina S, Fowler S. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med 2005; 142: 611-619 [PMID: 15838067]
39. Vilar Gomez E, Rodriguez De Miranda A, Gra Oramas B, Arus Soler E, Llanio Navarro R, Calzadilla Bertot L, Yasells Garcia A, Del Rosario Abreu Vazquez M. Clinical trial: a nutritional supplement Viusid, in combination with diet and exercise, in patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther 2009; 30: 999-1009 [PMID: 19691668 DOI: 10.1111/j.1365-2036.2009.04122.x]
40. Wang RT, Koretz RL, Yee HF. Is weight reduction an effective therapy for nonalcoholic fatty liver? A systematic review. Am J Med 2003; 115: 554-559 [PMID: 14599635]
41. Moscatiello S, Di Luzio R, Bugianesi E, Suppini A, Hickman IJ, Di Domizio S, Dalle Grave R, Marchesini G. Cognitive-behavioral treatment of nonalcoholic Fatty liver disease: a propensity score-adjusted observational study. Obesity (Silver Spring) 2011; 19: 763-770 [PMID: 20966900 DOI: 10.1038/oby.2010.254]
42. Moschen AR, Tilg H. Nutrition in pathophysiology and treatment of nonalcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care 2008; 11: 620-625 [PMID: 18685459 DOI: 10.1097/MCO.0b013e32830b5d09]
43. Bellentani S, Dalle Grave R, Suppini A, Marchesini G. Behavior therapy for nonalcoholic fatty liver disease: The need for a multidisciplinary approach. Hepatology 2008; 47: 746-754 [PMID: 18098321 DOI: 10.1002/hep.22009]
44. Neuschwander-Tetri BA. Lifestyle modification as the primary treatment of NASH. Clin Liver Dis 2009; 13: 649-665 [PMID: 19818311 DOI: 10.1016/j.cld.2009.07.006]
45. 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]
46. Park HS, Kim MW, Shin ES. Effect of weight control on hepatic abnormalities in obese patients with fatty liver. J Korean Med Sci 1995; 10: 414-421 [PMID: 8924225]
47. Palmer M, Schaffner F. Effect of weight reduction on hepatic abnormalities in overweight patients. Gastroenterology 1990; 99: 1408-1413 [PMID: 2210247]
48. Vajro P, Mandato C, Franzese A, Ciccimarra E, Lucariello S, Savoia M, Capuano G, Migliaro F. Vitamin E treatment in pediatric obesity-related liver disease: a randomized study. J Pediatr Gastroenterol Nutr 2004; 38: 48-55 [PMID: 14676594]
49. Huang MA, Greenson JK, Chao C, Anderson L, Peterman D, Jacobson J, Emick D, Lok AS, Conjeevaram HS. 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 [PMID: 15842581]
50. Hickman IJ, Jonsson JR, Prins JB, Ash S, Purdie DM, Clouston AD, Powell EE. Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut 2004; 53: 413-419 [PMID: 14960526]
51. Kugelmas M, Hill DB, Vivian B, Marsano L, McClain CJ. Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. Hepatology 2003; 38: 413-419 [PMID: 12883485 DOI: 10.1053/jhep.2003.50316]
52. Schäfer S, Kantartzis K, Machann J, Venter C, Niess A, Schick F, Machicao F, Häring HU, Fritsche A, Stefan N. Lifestyle intervention in individuals with normal versus impaired glucose tolerance. Eur J Clin Invest 2007; 37: 535-543 [PMID: 17576204 DOI: 10.1111/j.1365-2362.2007.01820.x]
53. Gasteyger C, Larsen TM, Vercruysse F, Astrup A. Effect of a dietary-induced weight loss on liver enzymes in obese subjects. Am J Clin Nutr 2008; 87: 1141-1147 [PMID: 18469232]
54. Ryan MC, Abbasi F, Lamendola C, Carter S, McLaughlin TL. Serum alanine aminotransferase levels decrease further with carbohydrate than fat restriction in insulin-resistant adults. Diabetes Care 2007; 30: 1075-1080 [PMID: 17351275 DOI: 10.2337/dc06-2169]
55. Browning JD, Baker JA, Rogers T, Davis J, Satapati S, Burgess SC. Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. Am J Clin Nutr 2011; 93: 1048-1052 [PMID: 21367948 DOI: 10.3945/ajcn.110.007674]
56. 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]
57. Andersen T, Gluud C, Franzmann MB, Christoffersen P. Hepatic effects of dietary weight loss in morbidly obese subjects. J Hepatol 1991; 12: 224-229 [PMID: 2051001]
58. Nobili V, Manco M, Devito R, Ciampalini P, Piemonte F, Marcellini M. Effect of vitamin E on aminotransferase levels and insulin resistance in children with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2006; 24: 1553-1561 [PMID: 17206944 DOI: 10.1111/j.1365-2036.2006.03161.x]
59. Suzuki A, Lindor K, St Saver J, Lymp J, Mendes F, Muto A, Okada T, Angulo P. Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J Hepatol 2005; 43: 1060-1066 [PMID: 16140415 DOI: 10.1016/j.jhep.2005.06.008]
60. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393-403 [PMID: 11832527 DOI: 10.1056/NEJMoa012512]
61. Knowler WC, Fowler SE, Hamman RF, Christophi CA, Hoffman HJ, Brenneman AT, Brown-Friday JO, Goldberg R, Venditti E, Nathan DM. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet 2009; 374: 1677-1686 [PMID: 19878986 DOI: 10.1016/S0140-6736(09)61457-4]
62. Rafiq N, Younossi ZM. Effects of weight loss on nonalcoholic fatty liver disease. Semin Liver Dis 2008; 28: 427-433 [PMID: 18956298 DOI: 10.1055/s-0028-1091986]
63. Clark JM. Weight loss as a treatment for nonalcoholic fatty liver disease. J Clin Gastroenterol 2006; 40 Suppl 1: S39-S43 [PMID: 16540766 DOI: 10.1097/01.mcg.0000168641.31321.fa]
64. Elias MC, Parise ER, de Carvalho L, Szejnfeld D, Netto JP. Effect of 6-month nutritional intervention on non-alcoholic fatty liver disease. Nutrition 2010; 26: 1094-1099 [PMID: 20022466 DOI: 10.1016/j.nut.2009.09.001]
65. 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]
66. Peng L, Wang J, Li F. Weight reduction for non-alcoholic fatty liver disease. Cochrane Database Syst Rev 2011; (6): CD003619 [PMID: 21678341 DOI: 10.1002/14651858.CD003619.pub3]
67. 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]
68. Mager DR, Patterson C, So S, Rogenstein CD, Wykes LJ, Roberts EA. Dietary and physical activity patterns in children with fatty liver. Eur J Clin Nutr 2010; 64: 628-635 [PMID: 20216561 DOI: 10.1038/ejcn.2010.35]
69. Krasnoff JB, Painter PL, Wallace JP, Bass NM, Merriman RB. Health-related fitness and physical activity in patients with nonalcoholic fatty liver disease. Hepatology 2008; 47: 1158-1166 [PMID: 18266250 DOI: 10.1002/hep.22137]
70. Johnson NA, Sachinwalla T, Walton DW, Smith K, Armstrong A, Thompson MW, George J. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology 2009; 50: 1105-1112 [PMID: 19637289 DOI: 10.1002/hep.23129]
71. Ismail I, Keating SE, Baker MK, Johnson NA. A systematic review and meta-analysis of the effect of aerobic vs. resistance exercise training on visceral fat. Obes Rev 2012; 13: 68-91 [PMID: 21951360 DOI: 10.1111/j.1467-789X.2011.00931.x]
72. Hayward C, Lockwood J, Williams C, Cole R, Torres D, Harrison S. Lifestyle Modification and NAFLD: A Prospective, Randomized Trial. Hepatology 2010; 52: 622A
73. Kistler KD, Brunt EM, Clark JM, Diehl AM, Sallis JF, Schwimmer JB. Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic fatty liver disease. Am J Gastroenterol 2011; 106: 460-48; quiz 469 [PMID: 21206486 DOI: 10.1038/ajg.2010.488]
74. Conjeevaram HS, Tiniakos DG. Editorial: Exercise for NAFLD: does intensity matter? Am J Gastroenterol 2011; 106: 470-475 [PMID: 21378763 DOI: 10.1038/ajg.2010.496]
75. Bae JC, Suh S, Park SE, Rhee EJ, Park CY, Oh KW, Park SW, Kim SW, Hur KY, Kim JH, Lee MS, Lee MK, Kim KW, Lee WY. Regular exercise is associated with a reduction in the risk of NAFLD and decreased liver enzymes in individuals with NAFLD independent of obesity in Korean adults. PLoS One 2012; 7: e46819 [PMID: 23110056 DOI: 10.1371/journal.pone.0046819]
76. 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 [PMID: 19444870 DOI: 10.1002/hep.22940]
77. Chan HL, de Silva HJ, Leung NW, Lim SG, Farrell GC. How should we manage patients with non-alcoholic fatty liver disease in 2007? J Gastroenterol Hepatol 2007; 22: 801-808 [PMID: 17565632 DOI: 10.1111/j.1440-1746.2007.04977.x]
78. Devries MC, Samjoo IA, Hamadeh MJ, Tarnopolsky MA. Effect of endurance exercise on hepatic lipid content, enzymes, and adiposity in men and women. Obesity (Silver Spring) 2008; 16: 2281-2288 [PMID: 18719669 DOI: 10.1038/oby.2008.358]
79. Keating SE, Hackett DA, George J, Johnson NA. Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 2012; 57: 157-166 [PMID: 22414768 DOI: 10.1016/j.jhep.2012.02.023]
80. Zelber-Sagi S, Kessler A, Brazowsky E, Webb M, Lurie Y, Santo M, Leshno M, Blendis L, Halpern Z, Oren R. A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2006; 4: 639-644 [PMID: 16630771 DOI: 10.1016/j.cgh.2006.02.004]
81. Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA. Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial. Hepatology 2009; 49: 80-86 [PMID: 19053049 DOI: 10.1002/hep.22575]
82. Neff LM, Aronne LJ. Pharmacotherapy for obesity. Curr Atheroscler Rep 2007; 9: 454-462 [PMID: 18377785]
83. Sabuncu T, Nazligul Y, Karaoglanoglu M, Ucar E, Kilic FB. The effects of sibutramine and orlistat on the ultrasonographic findings, insulin resistance and liver enzyme levels in obese patients with non-alcoholic steatohepatitis. Rom J Gastroenterol 2003; 12: 189-192 [PMID: 14502318]
84. Harrison SA, Neuschwander-Tetri BA. Pharmacologic management of nonalcoholic fatty liver disease. Clin Liver Dis 2004; 8: 715-28, xii [PMID: 15331071]
85. Sabuncu T, Harma M, Harma M, Nazligul Y, Kilic F. Sibutramine has a positive effect on clinical and metabolic parameters in obese patients with polycystic ovary syndrome. Fertil Steril 2003; 80: 1199-1204 [PMID: 14607575]
86. Filippatos TD, Elisaf MS. Combination drug treatment in patients with non-alcoholic fatty liver disease. World J Hepatol 2010; 2: 139-142 [PMID: 21160985 DOI: 10.4254/wjh.v2.i4.139]
87. James WP, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni AP, Torp-Pedersen C, Sharma AM, Shepherd GM, Rode RA, Renz CL. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 2010; 363: 905-917 [PMID: 20818901 DOI: 10.1056/NEJMoa1003114]
88. Scheen AJ. Cardiovascular risk-benefit profile of sibutramine. Am J Cardiovasc Drugs 2010; 10: 321-334 [PMID: 20860415]
89. Chavez-Tapia NC, Tellez-Avila FI, Bedogni G, Crocè LS, Masutti F, Tiribelli C. Systematic review and meta-analysis on the adverse events of rimonabant treatment: considerations for its potential use in hepatology. BMC Gastroenterol 2009; 9: 75 [PMID: 19818116 DOI: 10.1186/1471-230X-9-75]
90. Lee HK, Choi EB, Pak CS. The current status and future perspectives of studies of cannabinoid receptor 1 antagonists as anti-obesity agents. Curr Top Med Chem 2009; 9: 482-503 [PMID: 19689362]
91. Brolin RE. Bariatric surgery and long-term control of morbid obesity. JAMA 2002; 288: 2793-2796 [PMID: 12472304]
92. Sjöström L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B, Dahlgren S, Larsson B, Narbro K, Sjöström CD, Sullivan M, Wedel H. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004; 351: 2683-2693 [PMID: 15616203 DOI: 10.1056/NEJMoa035622]
93. Dixon JB, Bhathal PS, Hughes NR, O'Brien PE. Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss. Hepatology 2004; 39: 1647-1654 [PMID: 15185306 DOI: 10.1002/hep.20251]
94. 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: 1396-1402 [PMID: 18986848 DOI: 10.1016/j.cgh.2008.08.012]
95. Stephen S, Baranova A, Younossi ZM. Nonalcoholic fatty liver disease and bariatric surgery. Expert Rev Gastroenterol Hepatol 2012; 6: 163-171 [PMID: 22375522 DOI: 10.1586/egh.11.97]
96. De Ridder RJ, Schoon EJ, Smulders JF, van Hout GC, Stockbrügger RW, Koek GH. Review article: Non-alcoholic fatty liver disease in morbidly obese patients and the effect of bariatric surgery. Aliment Pharmacol Ther 2007; 26 Suppl 2: 195-201 [PMID: 18081662 DOI: 10.1111/j.1365-2036.2007.03483.x]
97. Hafeez S, Ahmed MH. Bariatric surgery as potential treatment for nonalcoholic fatty liver disease: a future treatment by choice or by chance? J Obes 2013; 2013: 839275 [PMID: 23431426 DOI: 10.1155/2013/839275]
98. Lee YM, Low HC, Lim LG, Dan YY, Aung MO, Cheng CL, Wee A, Lim SG, Ho KY. Intragastric balloon significantly improves nonalcoholic fatty liver disease activity score in obese patients with nonalcoholic steatohepatitis: a pilot study. Gastrointest Endosc 2012; 76: 756-760 [PMID: 22840293 DOI: 10.1016/j.gie.2012.05.023]
99. 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]
100. Ratziu V, Caldwell S, Neuschwander-Tetri BA. Therapeutic trials in nonalcoholic steatohepatitis: insulin sensitizers and related methodological issues. Hepatology 2010; 52: 2206-2215 [PMID: 21105109 DOI: 10.1002/hep.24042]
101. Rakoski MO, Singal AG, Rogers MA, Conjeevaram H. Metaanalysis: insulin sensitizers for the treatment of non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2010; 32: 1211-1221 [PMID: 20955440 DOI: 10.1111/j.1365-2036.2010.04467.x]
102. Socha P, Horvath A, Vajro P, Dziechciarz P, Dhawan A, Szajewska H. Pharmacological interventions for nonalcoholic fatty liver disease in adults and in children: a systematic review. J Pediatr Gastroenterol Nutr 2009; 48: 587-596 [PMID: 19412008 DOI: 10.1097/MPG.0b013e31818e04d1]
103. Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila FI, Sanchez-Avila F, Montano-Reyes MA, Uribe M. Insulin sensitizers in treatment of nonalcoholic fatty liver disease: Systematic review. World J Gastroenterol 2006; 12: 7826-7831 [PMID: 17203528]
104. Utzschneider KM, Kahn SE. Review: The role of insulin resistance in nonalcoholic fatty liver disease. J Clin Endocrinol Metab 2006; 91: 4753-4761 [PMID: 16968800 DOI: 10.1210/jc.2006-0587]
105. Moscatiello S, Marzocchi R, Villanova N, Bugianesi E, Marchesini G. Which treatment for nonalcoholic fatty liver disease? Mini Rev Med Chem 2008; 8: 767-775 [PMID: 18673132]
106. 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]
107. Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T, Doo E, Ghany M, Premkumar A, Park Y, Liang TJ, Yanovski JA, Kleiner DE, Hoofnagle JH. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology 2004; 39: 188-196 [PMID: 14752837]
108. 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]
109. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M, Melchionda N. Metformin in non-alcoholic steatohepatitis. Lancet 2001; 358: 893-894 [PMID: 11567710]
110. Schwimmer JB, Middleton MS, Deutsch R, Lavine JE. A phase 2 clinical trial of metformin as a treatment for nondiabetic paediatric non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2005; 21: 871-879 [PMID: 15801922]
111. 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]
112. Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N, David E, Rizzetto M, Marchesini G. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol 2005; 100: 1082-1090 [PMID: 15842582]
113. Garinis GA, Fruci B, Mazza A, De Siena M, Abenavoli S, Gulletta E, Ventura V, Greco M, Abenavoli L, Belfiore A. Metformin versus dietary treatment in nonalcoholic hepatic steatosis: a randomized study. Int J Obes (Lond) 2010; 34: 1255-1264 [PMID: 20179669 DOI: 10.1038/ijo.2010.40]
114. Angelico F, Burattin M, Alessandri C, Del Ben M, Lirussi F. Drugs improving insulin resistance for non-alcoholic fatty liver disease and/or non-alcoholic steatohepatitis. Cochrane Database Syst Rev 2007; (1): CD005166 [PMID: 17253544 DOI: 10.1002/14651858.CD005166.pub2]
115. Tock L, Dâmaso AR, de Piano A, Carnier J, Sanches PL, Lederman HM, Ernandes RM, de Mello MT, Tufik S. Longterm effects of metformin and lifestyle modification on nonalcoholic Fatty liver disease obese adolescents. J Obes 2010; 2010: pii 831901 [PMID: 20798858 DOI: 10.1155/2010/831901]
116. Lavine JE, Schwimmer JB, Molleston JP, Scheimann AO, Murray KF, Abrams SH, Rosenthal P, Sanyal AJ, Robuck PR, Brunt EM, Unalp A, Tonascia J. Treatment of nonalcoholic fatty liver disease in children: TONIC trial design. Contemp Clin Trials 2010; 31: 62-70 [PMID: 19761871 DOI: 10.1016/j.cct.2009.09.001]
117. Lavine JE, Schwimmer JB, Van Natta ML, Molleston JP, Murray KF, Rosenthal P, Abrams SH, Scheimann AO, Sanyal AJ, Chalasani N, Tonascia J, Ünalp A, Clark JM, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR. 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: 1659-1668 [PMID: 21521847 DOI: 10.1001/jama.2011.520]
118. Krakoff J, Clark JM, Crandall JP, Wilson C, Molitch ME, Brancati FL, Edelstein SL, Knowler WC. Effects of metformin and weight loss on serum alanine aminotransferase activity in the diabetes prevention program. Obesity (Silver Spring) 2010; 18: 1762-1767 [PMID: 20186137 DOI: 10.1038/oby.2010.21]
119. Shyangdan D, Clar C, Ghouri N, Henderson R, Gurung T, Preiss D, Sattar N, Fraser A, Waugh N. Insulin sensitisers in the treatment of non-alcoholic fatty liver disease: a systematic review. Health Technol Assess 2011; 15: 1-110 [PMID: 22059955 DOI: 10.3310/hta15380]
120. Yki-Järvinen H. Thiazolidinediones. N Engl J Med 2004; 351: 1106-1118 [PMID: 15356308 DOI: 10.1056/NEJMra041001]
121. Musso G, Gambino R, Cassader M, Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology 2010; 52: 79-104 [PMID: 20578268 DOI: 10.1002/hep.23623]
122. Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology 2003; 38: 1008-1017 [PMID: 14512888]
123. 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]
124. 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]
125. Gupta AK, Bray GA, Greenway FL, Martin CK, Johnson WD, Smith SR. Pioglitazone, but not metformin, reduces liver fat in Type-2 diabetes mellitus independent of weight changes. J Diabetes Complications 2010; 24: 289-296 [PMID: 19577936 DOI: 10.1016/j.jdiacomp.2009.05.004]
126. Ratziu V, Charlotte F, Bernhardt C, Giral P, Halbron M, Lenaour G, Hartmann-Heurtier A, Bruckert E, Poynard T. Long-term efficacy of rosiglitazone in nonalcoholic steatohepatitis: results of the fatty liver improvement by rosiglitazone therapy (FLIRT 2) extension trial. Hepatology 2010; 51: 445-453 [PMID: 19877169 DOI: 10.1002/hep.23270]
127. 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]
128. Boettcher E, Csako G, Pucino F, Wesley R, Loomba R. Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2012; 35: 66-75 [PMID: 22050199 DOI: 10.1111/j.1365-2036.2011.04912.x]
129. Taylor C, Hobbs FD. Type 2 diabetes, thiazolidinediones, and cardiovascular risk. Br J Gen Pract 2009; 59: 520-524 [PMID: 19567003 DOI: 10.3399/bjgp09X453440]
130. Zambon A, Cusi K. The role of fenofibrate in clinical practice. Diab Vasc Dis Res 2007; 4 Suppl 3: S15-S20 [PMID: 17935056 DOI: 10.3132/dvdr.2007.053]
131. Liberopoulos EN, Athyros VG, Elisaf MS, Mikhailidis DP. Statins for non-alcoholic fatty liver disease: a new indication? Aliment Pharmacol Ther 2006; 24: 698-699 [PMID: 16907904 DOI: 10.1111/j.1365-2036.2006.03021.x]
132. Basaranoglu M, Acbay O, Sonsuz A. A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis. J Hepatol 1999; 31: 384 [PMID: 10453959]
133. Laurin J, Lindor KD, Crippin JS, Gossard A, Gores GJ, Ludwig J, Rakela J, McGill DB. Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: a pilot study. Hepatology 1996; 23: 1464-1467 [PMID: 8675165 DOI: 10.1002/hep.510230624]
134. Fabbrini E, Mohammed BS, Korenblat KM, Magkos F, Mc-Crea J, Patterson BW, Klein S. Effect of fenofibrate and niacin on intrahepatic triglyceride content, very low-density lipoprotein kinetics, and insulin action in obese subjects with nonalcoholic fatty liver disease. J Clin Endocrinol Metab 2010; 95: 2727-2735 [PMID: 20371660 DOI: 10.1210/jc.2009-2622]
135. Athyros VG, Mikhailidis DP, Didangelos TP, Giouleme OI, Liberopoulos EN, Karagiannis A, Kakafika AI, Tziomalos K, Burroughs AK, Elisaf MS. Effect of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome: a randomised study. Curr Med Res Opin 2006; 22: 873-883 [PMID: 16709309 DOI: 10.1185/030079906X104696]
136. Hyogo H, Tazuma S, Arihiro K, Iwamoto K, Nabeshima Y, Inoue M, Ishitobi T, Nonaka M, Chayama K. Efficacy of atorvastatin for the treatment of nonalcoholic steatohepatitis with dyslipidemia. Metabolism 2008; 57: 1711-1718 [PMID: 19013295 DOI: 10.1016/j.metabol.2008.07.030]
137. Nelson A, Torres DM, Morgan AE, Fincke C, Harrison SA. A pilot study using simvastatin in the treatment of nonalcoholic steatohepatitis: A randomized placebo-controlled trial. J Clin Gastroenterol 2009; 43: 990-994 [PMID: 19448566 DOI: 10.1097/MCG.0b013e31819c392e]
138. Hatzitolios A, Savopoulos C, Lazaraki G, Sidiropoulos I, Haritanti P, Lefkopoulos A, Karagiannopoulou G, Tzioufa V, Dimitrios K. Efficacy of omega-3 fatty acids, atorvastatin and orlistat in non-alcoholic fatty liver disease with dyslipidemia. Indian J Gastroenterol 2004; 23: 131-134 [PMID: 15333967]
139. Kiyici M, Gulten M, Gurel S, Nak SG, Dolar E, Savci G, Adim SB, Yerci O, Memik F. Ursodeoxycholic acid and atorvastatin in the treatment of nonalcoholic steatohepatitis. Can J Gastroenterol 2003; 17: 713-718 [PMID: 14679419]
140. Abel T, Fehér J, Dinya E, Eldin MG, Kovács A. Safety and efficacy of combined ezetimibe/simvastatin treatment and simvastatin monotherapy in patients with non-alcoholic fatty liver disease. Med Sci Monit 2009; 15: MS6-M11 [PMID: 19946244]
141. Mihaila RG, Nedelcu L, Fratila O, Rezi EC, Domnariu C, Deac M. Effects of lovastatin and pentoxyphyllin in nonalcoholic steatohepatitis. Hepatogastroenterology 2009; 56: 1117-1121 [PMID: 19760953]
142. Rallidis LS, Drakoulis CK, Parasi AS. Pravastatin in patients with nonalcoholic steatohepatitis: results of a pilot study. Atherosclerosis 2004; 174: 193-196 [PMID: 15135271 DOI: 10.1016/j.atherosclerosis.2004.01.008]
143. Gómez-Domínguez E, Gisbert JP, Moreno-Monteagudo JA, García-Buey L, Moreno-Otero R. A pilot study of atorvastatin treatment in dyslipemid, non-alcoholic fatty liver patients. Aliment Pharmacol Ther 2006; 23: 1643-1647 [PMID: 16696815 DOI: 10.1111/j.1365-2036.2006.02926.x]
144. Foster T, Budoff MJ, Saab S, Ahmadi N, Gordon C, Guerci AD. Atorvastatin and antioxidants for the treatment of nonalcoholic fatty liver disease: the St Francis Heart Study randomized clinical trial. Am J Gastroenterol 2011; 106: 71-77 [PMID: 20842109 DOI: 10.1038/ajg.2010.299]
145. Chalasani N . Statins and hepatotoxicity: focus on patients with fatty liver. Hepatology 2005; 41: 690-695 [PMID: 15789367 DOI: 10.1002/hep.20671]
146. Vuppalanchi R, Teal E, Chalasani N. Patients with elevated baseline liver enzymes do not have higher frequency of hepatotoxicity from lovastatin than those with normal baseline liver enzymes. Am J Med Sci 2005; 329: 62-65 [PMID: 15711421]
147. 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]
148. Riley P, Al Bakir M, O'Donohue J, Crook M. Prescribing statins to patients with nonalcoholic fatty liver disease: real cardiovascular benefits outweigh theoretical hepatotoxic risk. Cardiovasc Ther 2009; 27: 216-220 [PMID: 19555426 DOI: 10.1111/j.1755-5922.2009.00088.x]
149. Athyros VG, Tziomalos K, Gossios TD, Griva T, Anagnostis P, Kargiotis K, Pagourelias ED, Theocharidou E, Karagiannis A, Mikhailidis DP. Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis. Lancet 2010; 376: 1916-1922 [PMID: 21109302 DOI: 10.1016/S0140-6736(10)61272-X]
150. Tzefos M, Olin JL. 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitor use in chronic liver disease: a therapeutic controversy. J Clin Lipidol 2011; 5: 450-459 [PMID: 22108148 DOI: 10.1016/j.jacl.2011.06.013]
151. Rudovich NN, Weickert MO, Machann J, Pfeiffer AF. Combination of acarbose and ezetimibe prevents non-alcoholic fatty liver disease: a break of intestinal insulin resistance? J Hepatol 2010; 52: 952-953 [PMID: 20385430 DOI: 10.1016/j.jhep.2010.02.004]
152. Enjoji M, Nakamuta M. Is the control of dietary cholesterol intake sufficiently effective to ameliorate nonalcoholic fatty liver disease? World J Gastroenterol 2010; 16: 800-803 [PMID: 20143458]
153. Zheng S, Hoos L, Cook J, Tetzloff G, Davis H, van Heek M, Hwa JJ. Ezetimibe improves high fat and cholesterol diet-induced non-alcoholic fatty liver disease in mice. Eur J Pharmacol 2008; 584: 118-124 [PMID: 18329014 DOI: 10.1016/j.ejphar.2008.01.045]
154. Nomura M, Ishii H, Kawakami A, Yoshida M. Inhibition of hepatic Niemann-Pick C1-like 1 improves hepatic insulin resistance. Am J Physiol Endocrinol Metab 2009; 297: E1030-E1038 [PMID: 19654286 DOI: 10.1152/ajpendo.00343.2009]
155. Ahmed MH, Byrne CD. Ezetimibe as a potential treatment for non-alcoholic fatty liver disease: is the intestine a modulator of hepatic insulin sensitivity and hepatic fat accumulation? Drug Discov Today 2010; 15: 590-595 [PMID: 20601094 DOI: 10.1016/j.drudis.2010.06.007]
156. Yamagishi S, Nakamura K, Matsui T, Sato T, Takeuchi M. Inhibition of intestinal cholesterol absorption by ezetimibe is a novel therapeutic target for fatty liver. Med Hypotheses 2006; 66: 844-846 [PMID: 16188393 DOI: 10.1016/j.mehy.2005.08.022]
157. Hughes EA, Tracey I, Singhal S, Patel J. Unexpected beneficial effect in the use of ezetimibe in non-alcoholic fatty liver disease. Med Hypotheses 2006; 67: 1463-1464 [PMID: 16831521 DOI: 10.1016/j.mehy.2006.05.041]
158. Patel JV, Hughes EA. Efficacy, safety and LDL-C goal attainment of ezetimibe 10 mg-simvastatin 20 mg vs. placebo-simvastatin 20 mg in UK-based adults with coronary heart disease and hypercholesterolaemia. Int J Clin Pract 2006; 60: 914-921 [PMID: 16893434 DOI: 10.1111/j.1742-1241.2006.01023.x]
159. Chan DC, Watts GF, Gan SK, Ooi EM, Barrett PH. Effect of ezetimibe on hepatic fat, inflammatory markers, and apolipoprotein B-100 kinetics in insulin-resistant obese subjects on a weight loss diet. Diabetes Care 2010; 33: 1134-1139 [PMID: 20185740 DOI: 10.2337/dc09-1765]
160. Enjoji M, Machida K, Kohjima M, Kato M, Kotoh K, Matsunaga K, Nakashima M, Nakamuta M. NPC1L1 inhibitor ezetimibe is a reliable therapeutic agent for non-obese patients with nonalcoholic fatty liver disease. Lipids Health Dis 2010; 9: 29 [PMID: 20222991 DOI: 10.1186/1476-511X-9-29]
161. Ahmed MH, Saad RA, Osman MM. Ezetimibe: effective and safe treatment for dyslipidaemia associated with nonalcoholic fatty liver disease. Response to: Toth PP, Davidson MH: simvastatin and ezetimibe: combination therapy for the management of dyslipidaemia. Expert Opin. Pharmacother. (2005) 6(1): 131-139. Expert Opin Drug Saf 2006; 5: 487-488 [PMID: 16774486 DOI: 10.1517/14740338.5.4.487]
162. Toth PP, Davidson MH. Simvastatin plus ezetimibe: combination therapy for the management of dyslipidaemia. Expert Opin Pharmacother 2005; 6: 131-139 [PMID: 15709890 DOI: 10.1517/14656566.6.1.131]
163. Yoneda M, Fujita K, Imajo K, Mawatari H, Kirikoshi H, Saito S, Nakajima A. Induction of microsomal triglyceride transfer protein expression is a candidate mechanism by which ezetimibe therapy might exert beneficial effects in patients with nonalcoholic steatohepatitis. J Gastroenterol 2011; 46: 415-46; author reply 417 [PMID: 21181211 DOI: 10.1007/s00535-010-0356-8]
164. Yoneda M, Fujita K, Nozaki Y, Endo H, Takahashi H, Hosono K, Suzuki K, Mawatari H, Kirikoshi H, Inamori M, Saito S, Iwasaki T, Terauchi Y, Kubota K, Maeyama S, Nakajima A. Efficacy of ezetimibe for the treatment of non-alcoholic steatohepatitis: An open-label, pilot study. Hepatol Res 2010; 40: 566-573 [PMID: 20412324 DOI: 10.1111/j.1872-034X.2010.00644.x]
165. Park H, Shima T, Yamaguchi K, Mitsuyoshi H, Minami M, Yasui K, Itoh Y, Yoshikawa T, Fukui M, Hasegawa G, Nakamura N, Ohta M, Obayashi H, Okanoue T. Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease. J Gastroenterol 2011; 46: 101-107 [PMID: 20658156 DOI: 10.1007/s00535-010-0291-8]
166. Yokohama S, Yoneda M, Haneda M, Okamoto S, Okada M, Aso K, Hasegawa T, Tokusashi Y, Miyokawa N, Nakamura K. Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology 2004; 40: 1222-1225 [PMID: 15382153]
167. Paschos P, Tziomalos K. Nonalcoholic fatty liver disease and the renin-angiotensin system: Implications for treatment. World J Hepatol 2012; 4: 327-331 [PMID: 23355909 DOI: 10.4254/wjh.v4.i12.327]
168. Georgescu EF, Ionescu R, Niculescu M, Mogoanta L, Vancica L. Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis. World J Gastroenterol 2009; 15: 942-954 [PMID: 19248193]
169. Eriksson JW, Jansson PA, Carlberg B, Hägg A, Kurland L, Svensson MK, Ahlström H, Ström C, Lönn L, Ojbrandt K, Johansson L, Lind L. Hydrochlorothiazide, but not Candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation: the mechanisms for the diabetes preventing effect of Candesartan (MEDICA) Study. Hypertension 2008; 52: 1030-1037 [PMID: 18981327 DOI: 10.1161/HYPERTENSIONAHA.108.119404]
170. Fogari R, Maffioli P, Mugellini A, Zoppi A, Lazzari P, Derosa G. Effects of losartan and amlodipine alone or combined with simvastatin in hypertensive patients with nonalcoholic hepatic steatosis. Eur J Gastroenterol Hepatol 2012; 24: 164-171 [PMID: 22081005 DOI: 10.1097/MEG.0b013e32834ba188]
171. Scheen AJ. Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 2. Overview of physiological and biochemical mechanisms. Diabetes Metab 2004; 30: 498-505 [PMID: 15671919]
172. Scheen AJ. Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials. Diabetes Metab 2004; 30: 487-496 [PMID: 15671918]
173. Vitale C, Mercuro G, Castiglioni C, Cornoldi A, Tulli A, Fini M, Volterrani M, Rosano GM. Metabolic effect of telmisartan and losartan in hypertensive patients with metabolic syndrome. Cardiovasc Diabetol 2005; 4: 6 [PMID: 15892894 DOI: 10.1186/1475-2840-4-6]
174. Sloniger JA, Saengsirisuwan V, Diehl CJ, Kim JS, Henriksen EJ. Selective angiotensin II receptor antagonism enhances whole-body insulin sensitivity and muscle glucose transport in hypertensive TG(mREN2)27 rats. Metabolism 2005; 54: 1659-1668 [PMID: 16311101 DOI: 10.1016/j.metabol.2005.06.016]
175. Loria P, Adinolfi LE, Bellentani S, Bugianesi E, Grieco A, Fargion S, Gasbarrini A, Loguercio C, Lonardo A, Marchesini G, Marra F, Persico M, Prati D, Baroni GS. 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 [PMID: 20171943 DOI: 10.1016/j.dld.2010.01.021]
176. 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 [PMID: 11564008]
177. Lavine JE. Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study. J Pediatr 2000; 136: 734-738 [PMID: 10839868]
178. Lirussi F, Azzalini L, Orando S, Orlando R, Angelico F. Antioxidant supplements for non-alcoholic fatty liver disease and/or steatohepatitis. Cochrane Database Syst Rev 2007; (1): CD004996 [PMID: 17253535]
179. 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]
180. Nobili V, Manco M, Devito R, Di Ciommo V, Comparcola D, Sartorelli MR, Piemonte F, Marcellini M, Angulo P. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: a randomized, controlled trial. Hepatology 2008; 48: 119-128 [PMID: 18537181 DOI: 10.1002/hep.22336]
181. 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: 1184-1188 [PMID: 19422479 DOI: 10.1111/j.1478-3231.2009.02037.x]
182. Kadayifci A, Merriman RB. Metformin, vitamin E, and diet for patients with nonalcoholic fatty liver disease. Am J Gastroenterol 2006; 101: 1396; author reply 1396-1397 [PMID: 16771968 DOI: 10.1111/j.1572-0241.2006.00595-1.x]
183. Ersöz G, Günşar F, Karasu Z, Akay S, Batur Y, Akarca US. Management of fatty liver disease with vitamin E and C compared to ursodeoxycholic acid treatment. Turk J Gastroenterol 2005; 16: 124-128 [PMID: 16245220]
184. Bernal-Reyes R, Escudero RB. [Treatment of non-alcoholic steatohepatitis (NASH). A comparative study of ursodeoxycholic acid and alpha-tocopherol. A preliminary report]. Rev Gastroenterol Mex 2002; 67: 70-75 [PMID: 12214337]
185. Dufour JF, Oneta CM, Gonvers JJ, Bihl F, Cerny A, Cereda JM, Zala JF, Helbling B, Steuerwald M, Zimmermann A. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 2006; 4: 1537-1543 [PMID: 17162245]
186. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 2007; 297: 842-857 [PMID: 17327526 DOI: 10.1001/jama.297.8.842]
187. Gerss J, Köpcke W. The questionable association of vitamin E supplementation and mortality - inconsistent results of different meta-analytic approaches. Cell Mol Biol (Noisy-legrand) 2009; 55 Suppl: OL1111-OL1120 [PMID: 19267994]
188. Parker HM, Johnson NA, Burdon CA, Cohn JS, O'Connor HT, George J. Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 2012; 56: 944-951 [PMID: 22023985 DOI: 10.1016/j.jhep.2011.08.018]
189. Koppe SW, Sahai A, Malladi P, Whitington PF, Green RM. Pentoxifylline attenuates steatohepatitis induced by the methionine choline deficient diet. J Hepatol 2004; 41: 592-598 [PMID: 15464239 DOI: 10.1016/j.jhep.2004.06.030]
190. Duman DG, Ozdemir F, Birben E, Keskin O, Ekşioʇlu-Demiralp E, Celikel C, Kalayci O, Kalayci C. Effects of pentoxifylline on TNF-alpha production by peripheral blood mononuclear cells in patients with nonalcoholic steatohepatitis. Dig Dis Sci 2007; 52: 2520-2524 [PMID: 17436095 DOI: 10.1007/s10620-006-9723-y]
191. Lee YM, Sutedja DS, Wai CT, Dan YY, Aung MO, Zhou L, Cheng CL, Wee A, Lim SG. A randomized controlled pilot study of Pentoxifylline in patients with non-alcoholic steatohepatitis (NASH). Hepatol Int 2008; 2: 196-201 [PMID: 19669304 DOI: 10.1007/s12072-008-9058-1]
192. Sturm N, Bronowicki JP, Maynard-Muet M, Tran A, Heluwaert F, Plages A, Zarski JP. Metformin plus pentoxifylline versus prescriptive diet in non-alcoholic steatohepatitis (NASH): a randomized controlled pilot trial. Gastroenterol Clin Biol 2009; 33: 984-986 [PMID: 19646832 DOI: 10.1016/j.gcb.2009.05.010]
193. Satapathy SK, Garg S, Chauhan R, Sakhuja P, Malhotra V, Sharma BC, Sarin SK. Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2004; 99: 1946-1952 [PMID: 15447754 DOI: 10.1111/j.1572-0241.2004.40220.x]
194. Satapathy SK, Sakhuja P, Malhotra V, Sharma BC, Sarin SK. Beneficial effects of pentoxifylline on hepatic steatosis, fibrosis and necroinflammation in patients with non-alcoholic steatohepatitis. J Gastroenterol Hepatol 2007; 22: 634-638 [PMID: 17444848 DOI: 10.1111/j.1440-1746.2006.04756.x]
195. Adams LA, Zein CO, Angulo P, Lindor KD. A pilot trial of pentoxifylline in nonalcoholic steatohepatitis. Am J Gastroenterol 2004; 99: 2365-2368 [PMID: 15571584 DOI: 10.1111/j.1572-0241.2004.40064.x]
196. Li W, Zheng L, Sheng C, Cheng X, Qing L, Qu S. Systematic review on the treatment of pentoxifylline in patients with non-alcoholic fatty liver disease. Lipids Health Dis 2011; 10: 49 [PMID: 21477300 DOI: 10.1186/1476-511X-10-49]
197. Buranawati W, Thoun-U-Thaisri, Pramoolsinsup C, Wisedopas N, Atamasirikul K, Udomsubpayakul U. Pentoxifylline for Treatment of Nonalcoholic Fatty Liver Disease (NAFLD): A Randomized, Placebo-Controlled Study. Thai J Gastroenterol 2007; 8: 57-63
198. Zein CO, Gogate P, Yerian L, Kirwan JP, McCullough A. Pentoxifylline Improves Nonalcoholic Steatohepatitis: Results of a Doubleblinded, Randomized, Placebo-Controlled Trial. Am J Gastroenterol 2010; 105 (Suppl 1): S114
199. Zein CO, Yerian LM, Gogate P, Lopez R, Kirwan JP, Feldstein AE, McCullough AJ. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology 2011; 54: 1610-1619 [PMID: 21748765 DOI: 10.1002/hep.24544]
200. Van Wagner LB, Koppe SW, Brunt EM, Gottstein J, Gardikiotes K, Green RM, Rinella ME. Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial. Ann Hepatol 2011; 10: 277-286 [PMID: 21677329]
201. Orlando R, Azzalini L, Orando S, Lirussi F. Bile acids for non-alcoholic fatty liver disease and/or steatohepatitis. Cochrane Database Syst Rev 2007; (1): CD005160 [PMID: 17253541 DOI: 10.1002/14651858.CD005160.pub2]
202. 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]
203. Leuschner UF, Lindenthal B, Herrmann G, Arnold JC, Rössle M, Cordes HJ, Zeuzem S, Hein J, Berg T. High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial. Hepatology 2010; 52: 472-479 [PMID: 20683947 DOI: 10.1002/hep.23727]
204. Kahn R, Davidson MB. The reality of type 2 diabetes prevention. Diabetes Care 2014; 37: 943-949 [PMID: 24652724 DOI: 10.2337/dc13-1954]
205. 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]
206. FDA. Information on Orlistat. 2010. Available from: URL: http://www.fda.gov/
207. Stinton LM, Loomba R. Recommendations for liver biopsy evaluation in non-alcoholic fatty liver disease. Minerva Gastroenterol Dietol 2014; 60: 5-13 [PMID: 24632764]
208. Teschke R, Frenzel C. Drug induced liver injury: do we still need a routine liver biopsy for diagnosis today? Ann Hepatol 2013; 13: 121-126 [PMID: 24378275]
209. Sumida Y, Nakajima A, Itoh Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol 2014; 20: 475-485 [PMID: 24574716 DOI: 10.3748/wjg.v20.i2.475]
210. Mosko JD, Nguyen GC. Increased perioperative mortality following bariatric surgery among patients with cirrhosis. Clin Gastroenterol Hepatol 2011; 9: 897-901 [PMID: 21782772 DOI: 10.1016/j.cgh.2011.07.007]
211. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC, Watson K, Wilson PW, Eddleman KM, Jarrett NM, La-Bresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC, Tomaselli GF. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129: S1-45 [PMID: 24222016 DOI: 10.1161/01.cir.0000437738.63853.7a]
212. Dasarathy S, Dasarathy J, Khiyami A, Yerian L, Hawkins C, Sargent R, McCullough AJ. Double-blind Randomized Placebo-controlled Clinical Trial of Omega 3 Fatty Acids for the Treatment of Diabetic Patients With Nonalcoholic Steatohepatitis. J Clin Gastroenterol 2014 Feb 27; Epub ahead of print [PMID: 24583757 DOI: 10.1097/MCG.0000000000000099]
213. Corrado RL, Torres DM, Harrison SA. Review of treatment options for nonalcoholic fatty liver disease. Med Clin North Am 2014; 98: 55-72 [PMID: 24266914 DOI: 10.1016/j.mcna.2013.09.001]
214. Du J, Ma YY, Yu CH, Li YM. Effects of pentoxifylline on nonalcoholic fatty liver disease: a meta-analysis. World J Gastroenterol 2014; 20: 569-577 [PMID: 24574727 DOI: 10.3748/wjg.v20.i2.569]
215. Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 2013; 10: 330-344 [PMID: 23507799 DOI: 10.1038/nrgastro.2013.41]
216. Goff DC, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R, Greenland P, Lackland DT, Levy D, O'Donnell CJ, Robinson JG, Schwartz JS, Shero ST, Smith SC, Sorlie P, Stone NJ, Wilson PW. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 63: 2935-2959 [PMID: 24239921 DOI: 10.1016/j.jacc.2013.11.005]
217. Eckel RH, Jakicic JM, Ard JD, de Jesus JM, Houston Miller N, Hubbard VS, Lee IM, Lichtenstein AH, Loria CM, Millen BE, Nonas CA, Sacks FM, Smith SC, Svetkey LP, Wadden TA, Yanovski SZ. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 63: 2960-2984 [PMID: 24239922 DOI: 10.1016/j.jacc.2013.11.003]
218. Scaglioni F, Marino M, Ciccia S, Procaccini A, Busacchi M, Loria P, Lonardo A, Malavolti M, Battistini NC, Pellegrini M, Carubbi F, Bellentani S. Short-term multidisciplinary nonpharmacological 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: 353-358 [PMID: 23273500 DOI: 10.1016/j.clinre.2012.10.009]
219. Tendler D, Lin S, Yancy WS, Mavropoulos J, Sylvestre P, Rockey DC, Westman EC. The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study. Dig Dis Sci 2007; 52: 589-593 [PMID: 17219068 DOI: 10.1007/s10620-006-9433-5]
220. Thomas EL, Brynes AE, Hamilton G, Patel N, Spong A, Goldin RD, Frost G, Bell JD, Taylor-Robinson SD. Effect of nutritional counselling on hepatic, muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease. World J Gastroenterol 2006; 12: 5813-5819 [PMID: 17007047]
221. Okita M, Hayashi M, Sasagawa T, Takagi K, Suzuki K, Kinoyama S, Ito T, Yamada G. Effect of a moderately energy-restricted diet on obese patients with fatty liver. Nutrition 2001; 17: 542-547 [PMID: 11448571]
222. Knobler H, Schattner A, Zhornicki T, Malnick SD, Keter D, Sokolovskaya N, Lurie Y, Bass DD. Fatty liver - an additional and treatable feature of the insulin resistance syndrome. QJM 1999; 92: 73-79 [PMID: 10209658]
223. Eriksson S, Eriksson KF, Bondesson L. Nonalcoholic steatohepatitis in obesity: a reversible condition. Acta Med Scand 1986; 220: 83-88 [PMID: 3766211]