Treatment of non-alcoholic fatty liver disease with focus on emerging drugs

Expert Opinion on Emerging Drugs

Volumn 16, Issue 1, 2011, Pages 121-136

  Marchesini, Giulio ^a   Moscatiello, Simona ^a   Agostini, Federica ^a   Villanova, Nicola ^a   Festi, Davide ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

angiotensin receptor blockers; antioxidants; cytoprotective agents; incretins; insulin sensitizers; non alcoholic fatty liver; weight loss

Indexed keywords

ACARBOSE; ALPHA TOCOPHEROL; ANTILIPEMIC AGENT; ANTIOXIDANT; ARAMCHOL; ASCORBIC ACID; ASP 9831; ATORVASTATIN; BERBERINE; BETAINE; BIGUANIDE DERIVATIVE; CANNABINOID RECEPTOR ANTAGONIST; CLOFIBRATE; EFAMAX; FENOFIBRATE; GEMFIBROZIL; GLITAZONE DERIVATIVE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INSULIN; INSULIN SENSITIZING AGENT; LOSARTAN; METFORMIN; OBETICHOLIC ACID; OMEGA 3 FATTY ACID ESTER; PIOGLITAZONE; PRAVASTATIN; PROTAMDIN; PROWHEY 94 CFM; RIMONABANT; ROSIGLITAZONE; ROSUVASTATIN; SIBUTRAMINE; SILIBININ PHOSPHATIDYLCHOLINE COMPLEX; SIMVASTATIN; TETRAHYDROLIPSTATIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; URSODEOXYCHOLIC ACID;

ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; BARIATRIC SURGERY; BEHAVIOR THERAPY; BILIOPANCREATIC BYPASS; CARDIOVASCULAR DISEASE; CLINICAL PROTOCOL; CLINICAL TRIAL (TOPIC); COHORT ANALYSIS; DEPRESSION; DIABETES MELLITUS; DIET THERAPY; DISEASE COURSE; DISEASE SEVERITY; DRUG COST; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ECHOGRAPHY; END STAGE LIVER DISEASE; EXERCISE; FATTY LIVER; FLUID RETENTION; HEART FAILURE; HISTOPATHOLOGY; HUMAN; HYPERINSULINEMIA; HYPERLIPIDEMIA; IMMUNOMODULATION; INSULIN RESISTANCE; ISCHEMIC HEART DISEASE; LIFESTYLE MODIFICATION; LIVER BIOPSY; LIVER CIRRHOSIS; LIVER DISEASE; LIVER FIBROSIS; LIVER FUNCTION TEST; LIVER INJURY; LIVER METABOLISM; LOW CALORY DIET; MENTAL DISEASE; METABOLIC SYNDROME X; MUSCLE DISEASE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; OUTCOME ASSESSMENT; OXIDATIVE STRESS; PATIENT COUNSELING; PHYSICAL ACTIVITY; RANDOMIZED CONTROLLED TRIAL; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; RISK FACTOR; SIDE EFFECT; STOMACH BYPASS; TREATMENT INDICATION; TREATMENT OUTCOME; WEIGHT REDUCTION;

ANIMALS; ANTI-OBESITY AGENTS; ANTIOXIDANTS; BARIATRIC SURGERY; BODY WEIGHT; CLINICAL TRIALS AS TOPIC; DIET THERAPY; DRUG DISCOVERY; FATTY LIVER; HUMANS; HYPOLIPIDEMIC AGENTS; INSULIN RESISTANCE; OBESITY; OXIDATIVE STRESS; THIAZOLIDINEDIONES; TREATMENT OUTCOME;

EID: 79952125791     PISSN: 14728214     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728214.2011.531700     Document Type: Review

References (100)

1. Clark JM. The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol 2006;16:S5-10 (Pubitemid 44309537)
2. Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003;37:917-23 (Pubitemid 36397405) (Pubitemid 36397405)
3. Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008;40:1461-5
4. Speliotes EK, Butler JL, Palmer CD, et al. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease. Hepatology 2010;52:904-12
5. 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;47:711-17 (Pubitemid 47503432) (Pubitemid 47503432)
6. Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R, et al. Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study. Hepatology 2008;48:1791-8
7. Newton JL, Jones DE, Henderson E, et al. Fatigue in non-alcoholic fatty liver disease (NAFLD) is significant and associates with inactivity and excessive daytime sleepiness but not with liver disease severity or insulin resistance. Gut 2008;57:807-13 (Pubitemid 351716975) (Pubitemid 351716975)
8. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002;287:356-9 (Pubitemid 34251969) (Pubitemid 34251969)
9. 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;53:372-84
10. Bugianesi E, Leone N, Vanni E, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002;123:134-40 (Pubitemid 34747534) (Pubitemid 34747534)
11. Ascha MS, Hanouneh IA, Lopez R, et al. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 2010;51:1972-8
12. Targher G, Marra F, Marchesini G. Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon? Diabetologia 2008;51:1947-53
13. Fracanzani AL, Burdick L, Raselli S, et al. Carotid artery intima-media thickness in nonalcoholic fatty liver disease. Am J Med 2008;121:72-8
14. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 2010;363:1341-50
15. Ghouri N, Preiss D, Sattar N. Liver enzymes, nonalcoholic fatty liver disease, and incident cardiovascular disease: a narrative review and clinical perspective of prospective data. Hepatology 2010;52:1156-61
16. Ekstedt M, Franzen LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006;44:865-73 (Pubitemid 46489550) (Pubitemid 46489550)
17. Dam-Larsen S, Franzmann M, Andersen IB, et al. Long term prognosis of fatty liver: risk of chronic liver disease and death. Gut 2004;53:750-5 (Pubitemid 38561456) (Pubitemid 38561456)
18. Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 2006;43:S99-112
19. Hickman IE, Jonsson JR, Prins JB, et al. 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;53:413-19 (Pubitemid 38241340) (Pubitemid 38241340)
20. Huang MA, Greenson JK, Chao C, et al. One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study. Am J Gastroenterol 2005;100:1072-81 (Pubitemid 40769044) (Pubitemid 40769044)
21. Suzuki A, Lindor K, St Sauver J, et al. Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J Hepatol 2005;43:1060-6 (Pubitemid 41627993) (Pubitemid 41627993)
22. Moscatiello S, Di Luzio R, Bugianesi E, et al. Cognitive-behavioral treatment of non-alcoholic fatty liver disease: a propensity score-adjusted observational study. Obesity (Silver Spring) 2011; In press
23. Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010;51:121-9
24. Klein S. Gastrointestinal surgery for obesity: a question of life and death and expertise. Gastroenterology 2006;130:630 (Pubitemid 43374510) (Pubitemid 43374510)
25. Angulo P. NAFLD, obesity, and bariatric surgery. Gastroenterology 2006;130:1848-52 (Pubitemid 43668867) (Pubitemid 43668867)
26. Dixon JB, Bhathal PS, O'Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 2001;121:91-100 (Pubitemid 32591518) (Pubitemid 32591518)
27. Klein S, Mittendorfer B, Eagon JC, et al. Gastric bypass surgery improves metabolic and hepatic abnormalities associated with nonalcoholic fatty liver disease. Gastroenterology 2006;130:1564-72 (Pubitemid 43668832) (Pubitemid 43668832)
28. Mathurin P, Gonzalez F, Kerdraon O, et al. The evolution of severe steatosis after bariatric surgery is related to insulin resistance. Gastroenterology 2006;130:1617-24 (Pubitemid 43668847) (Pubitemid 43668847)
29. Kral JG, Thung SN, Biron S, et al. Effects of surgical treatment of the metabolic syndrome on liver fibrosis and cirrhosis. Surgery 2004;135:48-58 (Pubitemid 38041453) (Pubitemid 38041453)
30. Sabuncu T, Nazligul Y, Karaoglanoglu M, et al. 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;12:189-92 (Pubitemid 37152602) (Pubitemid 37152602)
31. Harrison SA, Fincke C, Helinski D, et al. A pilot study of orlistat treatment in obese, non-alcoholic steatohepatitis patients. Aliment Pharmacol Ther 2004;20:623-8 (Pubitemid 39279050) (Pubitemid 39279050)
32. Hatzitolios A, Savopoulos C, Lazaraki G, et al. Efficacy of omega-3 fatty acids, atorvastatin and orlistat in non-alcoholic fatty liver disease with dyslipidemia. Indian J Gastroenterol 2004;23:131-4 (Pubitemid 39145721) (Pubitemid 39145721)
33. Harrison SA, Fecht W, Brunt EM, et al. Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial. Hepatology 2009;49:80-6
34. Gary-Bobo M, Elachouri G, Gallas JF, et al. Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic syndrome in obese Zucker fa/fa rats. Hepatology 2007;46:122-9 (Pubitemid 47171928) (Pubitemid 47171928)
35. Despres JP, Golay A, Sjostrom L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005;353:2121-34 (Pubitemid 41653104) (Pubitemid 41653104)
36. Janero DR, Makriyannis A. Cannabinoid receptor antagonists: pharmacological opportunities, clinical experience, and translational prognosis. Expert Opin Emerg Drugs 2009;14:43-65
37. James WP, Caterson ID, Coutinho W, et al. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 2010;363:905-17
38. Wadden TA, Berkowitz RI, Womble LG, et al. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N Engl J Med 2005;353:2111-20 (Pubitemid 41653103) (Pubitemid 41653103)
39. Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2010;376:595-605
40. Belfort R, Harrison SA, Brown K, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006;355:2297-307 (Pubitemid 44837778) (Pubitemid 44837778)
41. Marchesini G, Brizi M, Bianchi G, et al. Metformin in non-alcoholic steatohepatitis. Lancet 2001;358:893-4 (Pubitemid 32900577) (Pubitemid 32900577)
42. Tiikkainen M, Hakkinen AM, Korsheninnikova E, et al. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes 2004;53:2169-76 (Pubitemid 38970772) (Pubitemid 38970772)
43. Promrat K, Lutchman G, Uwaifo GI, et al. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology 2004;39:188-96 (Pubitemid 38461481) (Pubitemid 38461481)
44. Lutchman G, Modi A, Kleiner DE, et al. The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology 2007;46:424-9 (Pubitemid 47344777) (Pubitemid 47344777)
45. Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes - an interim analysis. N Engl J Med 2007;357:28-8
46. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007;356:2457-71 (Pubitemid 46919772) (Pubitemid 46919772)
47. Argo CK, Loria P, Caldwell SH, et al. Statins in liver disease: a molehill, an iceberg, or neither? Hepatology 2008;48:662-9
48. Chalasani N. Statins and hepatotoxicity: focus on patients with fatty liver. Hepatology 2005;41:690-5 (Pubitemid 40462927) (Pubitemid 40462927)
49. Rallidis LS, Drakoulis CK, Parasi AS. Pravastatin in patients with nonalcoholic steatohepatitis: results of a pilot study. Atherosclerosis 2004;174:193-6 (Pubitemid 38595458) (Pubitemid 38595458)
50. Antonopoulos S, Mikros S, Mylonopoulou M, et al. Rosuvastatin as a novel treatment of non-alcoholic fatty liver disease in hyperlipidemic patients. Atherosclerosis 2006;184:233-4 (Pubitemid 41721093) (Pubitemid 41721093)
51. Perger L, Kohler M, Fattinger K, et al. Fatal liver failure with atorvastatin. J Hepatol 2003;39:1095-7
52. Comar KM, Sterling RK. Review article: drug therapy for non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2006;23:207-15 (Pubitemid 43382029) (Pubitemid 43382029)
53. Gomez-Dominguez E, Gisbert JP, Moreno-Monteagudo JA, et al. A pilot study of atorvastatin treatment in dyslipemic, non-alcoholic fatty liver patients. Aliment Pharmacol Ther 2006;23:1643-7 (Pubitemid 43727474) (Pubitemid 43727474)
54. 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;43:990-4
55. Laurin J, Lindor KD, Crippin JS, et al. Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: a pilot study. Hepatology 1996;23:1464-7
56. Basaranoglu M, Acbay O, Sonsuz A. A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis. J Hepatol 1999;31:384 (Pubitemid 29349772) (Pubitemid 29349772)
57. Vajro P, Mandato C, Franzese A, et al. Vitamin E treatment in pediatric obesity-related liver disease: a randomized study. J Pediatr Gastroenterol Nutr 2004;38:48-55 (Pubitemid 39274467) (Pubitemid 39274467)
58. Kugelmas M, Hill DB, Vivian B, et al. Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. Hepatology 2003;38:413-19 (Pubitemid 36919862) (Pubitemid 36919862)
59. Hasegawa T, Yoneda M, Nakamura K, et al. Plasma transforming growth factor-beta1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Aliment Pharmacol Ther 2001;15:1667-72 (Pubitemid 32912411) (Pubitemid 32912411)
60. Harrison SA, Torgerson S, Hayashi P, et al. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2003;98:2485-90 (Pubitemid 37448761) (Pubitemid 37448761)
61. Bugianesi E, Gentilcore E, Manini R, et al. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol 2005;100:1082-90 (Pubitemid 40769045) (Pubitemid 40769045)
62. Madan K, Batra Y, Gupta DS, et al. Vitamin E-based therapy is effective in ameliorating transaminasemia in nonalcoholic fatty liver disease. Indian J Gastroenterol 2005;24:251-5 (Pubitemid 44326097) (Pubitemid 44326097)
63. Dufour JF, Oneta CM, Gonvers JJ, et al. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin E in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 2006;4:1537-43 (Pubitemid 44880031) (Pubitemid 44880031)
64. Sanyal AJ, Mofrad PS, Contos MJ, et al. A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 2004;2:1107-15 (Pubitemid 40037642) (Pubitemid 40037642)
65. Chalasani NP, Sanyal AJ, Kowdley KV, et al. Pioglitazone versus vitamin E versus placebo for the treatment of non-diabetic patients with non-alcoholic steatohepatitis: PIVENS trial design. Contemp Clin Trials 2009;30:88-96
66. Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010;362:1675-85
67. Abdelmalek M, Angulo P, Jorgensen RA, et al. Betaine for patients with non-alcoholic steatohepatitis: a promising new agent. Gastroenterology 2000;118:A973
68. Miglio F, Rovati LC, Santoro A, et al. Efficacy and safety of oral betaine glucuronate in non-alcoholic steatohepatitis. A double-blind, randomized, parallel-group, placebo-controlled prospective clinical study. Arzneimittelforschung 2000;50:722-7 (Pubitemid 30642806) (Pubitemid 30642806)
69. Santos VN, Lanzoni VP, Szejnfeld J, et al. 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;36:723-9 (Pubitemid 36874723) (Pubitemid 36874723)
70. Mendez-Sanchez N, Gonzalez V, Chavez-Tapia N, et al. Weight reduction and ursodeoxycholic acid in subjects with nonalcoholic fatty liver disease. A double-blind, placebo-controlled trial. Ann Hepatol 2004;3:108-12
71. Lindor KD, Kowdley KV, Heathcote EJ, et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 2004;39:770-8 (Pubitemid 38337657) (Pubitemid 38337657)
72. Yoshiji H, Kuriyama S, Yoshii J, et al. Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats. Hepatology 2001;34:745-50 (Pubitemid 32927999) (Pubitemid 32927999)
73. Fujita K, Yoneda M, Wada K, et al. Telmisartan, an angiotensin II type 1 receptor blocker, controls progress of nonalcoholic steatohepatitis in rats. Dig Dis Sci 2007;52:3455-64 (Pubitemid 350077187) (Pubitemid 350077187)
74. Yokohama S, Yoneda M, Haneda M, et al. Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology 2004;40:1222-5 (Pubitemid 39425579) (Pubitemid 39425579)
75. Georgescu EF, Georgescu M. Therapeutic options in non-alcoholic steatohepatitis (NASH). Are all agents alike? Results of a preliminary study. J Gastrointestin Liver Dis 2007;16:39-46 (Pubitemid 46548588) (Pubitemid 46548588)
76. Georgescu EF, Ionescu R, Niculescu M, et al. Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis. World J Gastroenterol 2009;15:942-54
77. Georgescu EF. Angiotensin receptor blockers in the treatment of NASH/NAFLD: could they be a first-class option? Adv Ther 2008;25:1141-74
78. Eng J, Kleinman WA, Singh L, et al. Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem 1992;267:7402-5
79. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006;368:1696-705 (Pubitemid 46048557) (Pubitemid 46048557)
80. Mudaliar S, Henry RR. Effects of incretin hormones on beta-cell mass and function, body weight, and hepatic and myocardial function. Am J Med 2010;123:S19-27
81. Lee YS, Shin S, Shigihara T, et al. Glucagon-like peptide-1 gene therapy in obese diabetic mice results in long-term cure of diabetes by improving insulin sensitivity and reducing hepatic gluconeogenesis. Diabetes 2007;56:1671-9 (Pubitemid 46842602) (Pubitemid 46842602)
82. Ding X, Saxena NK, Lin S, et al. Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology 2006;43:173-81 (Pubitemid 43733604) (Pubitemid 43733604)
83. D'Alessio DA, Kahn SE, Leusner CR, et al. Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal. J Clin Invest 1994;93:2263-6 (Pubitemid 24143111) (Pubitemid 24143111)
84. Klonoff DC, Buse JB, Nielsen LL, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 2008;24:275-86 (Pubitemid 351160260) (Pubitemid 351160260)
85. Tushuizen ME, Bunck MC, Pouwels PJ, et al. Incretin mimetics as a novel therapeutic option for hepatic steatosis. Liver Int 2006;26:1015-17 (Pubitemid 44323421) (Pubitemid 44323421)
86. Szczepaniak LS, Nurenberg P, Leonard D, et al. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 2005;288:E462-8 (Pubitemid 40110657)
87. Gupta NA, Mells J, Dunham RM, et al. Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway. Hepatology 2010;51:1584-92
88. Li Z, Yang S, Lin H, et al. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology 2003;37:343-50 (Pubitemid 36152533) (Pubitemid 36152533)
89. 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;39:540-3 (Pubitemid 40863651) (Pubitemid 40863651)
90. Velayudham A, Dolganiuc A, Ellis M, et al. VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatology 2009;49:989-97
91. Kim WS, Lee YS, Cha SH, et al. Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity. Am J Physiol Endocrinol Metab 2009;296:E812-19
92. Liu LZ, Cheung SC, Lan LL, et al. Berberine modulates insulin signaling transduction in insulin-resistant cells. Mol Cell Endocrinol 2010;317:148-53
93. Chang X, Yan H, Fei J, et al. Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats. J Lipid Res 2010;51:2504-15
94. Samuel VT, Liu ZX, Wang A, et al. Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease. J Clin Invest 2007;117:739-45 (Pubitemid 46348532) (Pubitemid 46348532)
95. Cariou B. The farnesoid X receptor (FXR) as a new target in non-alcoholic steatohepatitis. Diabetes Metab 2008;34:685-91
96. Zhang S, Wang J, Liu Q, et al. Farnesoid X receptor agonist WAY-362450 attenuates liver inflammation and fibrosis in murine model of non-alcoholic steatohepatitis. J Hepatol 2009;51:380-8
97. Leclercq IA, Farrell GC, Sempoux C, et al. Curcumin inhibits NF-kappaB activation and reduces the severity of experimental steatohepatitis in mice. J Hepatol 2004;41:926-34 (Pubitemid 39575659) (Pubitemid 39575659)
98. Satapathy SK, Sakhuja P, Malhotra V, et al. Beneficial effects of pentoxifylline on hepatic steatosis, fibrosis and necroinflammation in patients with non-alcoholic steatohepatitis. J Gastroenterol Hepatol 2007;22:634-8 (Pubitemid 46608380) (Pubitemid 46608380)
99. Syn WK, Jung Y, Omenetti A, et al. Hedgehog-mediated epithelial-to- mesenchymal transition and fibrogenic repair in nonalcoholic fatty liver disease. Gastroenterology 2009;137:1478-88 e8
100. Syn WK, Oo YH, Pereira TA, et al. Accumulation of natural killer T cells in progressive nonalcoholic fatty liver disease. Hepatology 2010;51:1998-2007.