Review: Advances in the treatment of nonalcoholic fatty liver disease

Therapeutic Advances in Endocrinology and Metabolism

Volumn 1, Issue 3, 2010, Pages 101-115

  Mehta, Sanjeev R ^a  

^a EALING HOSPITAL NHS TRUST   (United Kingdom)

Author keywords

insulin resistance; metabolic syndrome; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; obesity; treatment; type 2 diabetes

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ACETYLCYSTEINE; ALPHA TOCOPHEROL; ANGIOTENSIN RECEPTOR ANTAGONIST; ANTIOXIDANT; ASCORBIC ACID; ATORVASTATIN; BETAINE; CLOFIBRATE; FENOFIBRATE; FIBRIC ACID DERIVATIVE; FRUCTOSE OLIGOSACCHARIDE; GEMFIBROZIL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INCRETIN; INSULIN; METFORMIN; PENTOXIFYLLINE; PHOSPHATIDYLCHOLINE; PIOGLITAZONE; PLACEBO; POLYUNSATURATED FATTY ACID; PROBIOTIC AGENT; RAMIPRIL; ROSIGLITAZONE; SIBUTRAMINE; SULFONYLUREA DERIVATIVE; TETRAHYDROLIPSTATIN; UNINDEXED DRUG; URSODEOXYCHOLIC ACID;

ALGORITHM; ARTICLE; BARIATRIC SURGERY; BEHAVIOR THERAPY; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; COST EFFECTIVENESS ANALYSIS; DIABETES MELLITUS; DIET THERAPY; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG SAFETY; DYSLIPIDEMIA; EXERCISE; FATTY LIVER; GASTRIC BANDING; HIGH RISK PATIENT; HUMAN; HYPERGLYCEMIA; HYPERTENSION; INSULIN RESISTANCE; LIFESTYLE MODIFICATION; LIVER FAILURE; LIVER TRANSPLANTATION; MALABSORPTION; MORTALITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; PATHOGENESIS; PRIORITY JOURNAL; PROGNOSIS; ROUX Y ANASTOMOSIS; WEIGHT REDUCTION;

EID: 79952822305     PISSN: 20420188     EISSN: None     Source Type: Journal    
DOI: 10.1177/2042018810379587     Document Type: Review

References (114)

1. Abdelmalek, M.F., Angulo, P., Jorgensen, R.A., Sylvestre, P.B. and Lindor, K.D. ( 2001) Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am J Gastroenterol 96: 2711-2717.
2. Adams, L.A., Angulo, P. and Lindor, K.D. ( 2005) Nonalcoholic fatty liver disease. Cmaj 172: 899-905.
3. Adams, L.A., Zein, C.O., Angulo, P. and Lindor, K.D. ( 2004) A pilot trial of pentoxifylline in nonalcoholic steatohepatitis. Am J Gastroenterol 99: 2365-2368.
4. Aithal, G.P., Thomas, J.A., Kaye, P.V., Lawson, A., Ryder, S.D., Spendlove, I. et al (2008) Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology 135: 1176-1184.
5. Andersen, T., Gluud, C., Franzmann, M.B. and Christoffersen, P. ( 1991) Hepatic effects of dietary weight loss in morbidly obese subjects. J Hepatol 12: 224-229.
6. Angulo, P. ( 2002) Nonalcoholic fatty liver disease. N Engl J Med 346: 1221-1231.
7. Araya, J., Rodrigo, R., Videla, L.A., Thielemann, L., Orellana, M., Pettinelli, P. et al (2004) Increase in long-chain polyunsaturated fatty acid n - 6/n - 3 ratio in relation to hepatic steatosis in patients with nonalcoholic fatty liver disease. Clin Sci (Lond) 106: 635-643.
8. Assy, N., Kaita, K., Mymin, D., Levy, C., Rosser, B. and Minuk, G. ( 2000) Fatty infiltration of liver in hyperlipidemic patients. Dig Dis Sci 45: 1929-1934.
9. Barker, K.B., Palekar, N.A., Bowers, S.P., Goldberg, J.E., Pulcini, J.P. and Harrison, S.A. ( 2006) Nonalcoholic steatohepatitis: effect of Roux-en-Y gastric bypass surgery. Am J Gastroenterol 101: 368-373.
10. Basaranoglu, M., Acbay, O. and Sonsuz, A. ( 1999) A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis. J Hepatol 31: 384.
11. Bedogni, G., Miglioli, L., Masutti, F., Tiribelli, C., Marchesini, G. and Bellentani, S. ( 2005) Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 42: 44-52.
12. Belfort, R., Harrison, S.A., Brown, K., Darland, C., Finch, J., Hardies, J. et al (2006) A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 355: 2297-2307.
13. Browning, J.D. ( 2006) Statins and hepatic steatosis: perspectives from the Dallas Heart Study. Hepatology 44: 466-471.
14. Browning, J.D., Davis, J., Saboorian, M.H. and Burgess, S.C. ( 2006) A low-carbohydrate diet rapidly and dramatically reduces intrahepatic triglyceride content. Hepatology 44: 487-488.
15. Browning, J.D., Szczepaniak, L.S., Dobbins, R., Nuremberg, P., Horton, J.D., Cohen, J.C. et al (2004) Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40: 1387-1395.
16. Buchman, A.L., Dubin, M., Jenden, D., Moukarzel, A., Roch, M.H., Rice, K. et al (1992) Lecithin increases plasma free choline and decreases hepatic steatosis in long-term total parenteral nutrition patients. Gastroenterology 102: 1363-1370.
17. Bugianesi, E., Gentilcore, E., Manini, R., Natale, S., Vanni, E., Villanova, N. et al (2005) A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol 100: 1082-1090.
18. Capanni, M., Calella, F., Biagini, M.R., Genise, S., Raimondi, L., Bedogni, G. et al (2006) Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study. Aliment Pharmacol Ther 23: 1143-1151.
19. Chang, C.Y., Argo, C.K., Al-Osaimi, A.M. and Caldwell, S.H. ( 2006) Therapy of NAFLD: antioxidants and cytoprotective agents. J Clin Gastroenterol 40(Suppl 1): S51-S60.
20. Charlton, M., Kasparova, P., Weston, S., Lindor, K., Maor-Kendler, Y., Wiesner, R.H. et al (2001) Frequency of nonalcoholic steatohepatitis as a cause of advanced liver disease. Liver Transpl 7: 608-614.
21. Clark, J.M., Alkhuraishi, A.R., Solga, S.F., Alli, P., Diehl, A.M. and Magnuson, T.H. ( 2005) Roux-en-Y gastric bypass improves liver histology in patients with non-alcoholic fatty liver disease. Obes Res 13: 1180-1186.
22. Contos, M.J., Cales, W., Sterling, R.K., Luketic, V.A., Shiffman, M.L., Mills, A.S. et al (2001) Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis. Liver Transpl 7: 363-373.
23. Daubioul, C.A., Horsmans, Y., Lambert, P., Danse, E. and Delzenne, N.M. ( 2005) Effects of oligofructose on glucose and lipid metabolism in patients with nonalcoholic steatohepatitis: results of a pilot study. Eur J Clin Nutr 59: 723-726.
24. Daubioul, C.A., Taper, H.S., de Wispelaere, L.D. and Delzenne, N.M. ( 2000) Dietary oligofructose lessens hepatic steatosis, but does not prevent hypertriglyceridemia in obese zucker rats. J Nutr 130: 1314-1319.
25. Day, C.P. ( 2005) Natural history of NAFLD: remarkably benign in the absence of cirrhosis. Gastroenterology 129: 375-378.
26. Day, C.P. ( 2006) From fat to inflammation. Gastroenterology 130: 207-210.
27. Day, C.P. and James, O.F. ( 1998) Steatohepatitis: a tale of two “hits”? Gastroenterology 114: 842-845.
28. de Almeida, S.R., Rocha, P.R., Sanches, M.D., Leite, V.H., da Silva, R.A., Diniz, M.T. et al (2006) Rouxen-Y gastric bypass improves the nonalcoholic steatohepatitis (NASH) of morbid obesity. Obes Surg 16: 270-278.
29. Demetriou, A.A. ( 1992) Lecithin increases plasma free choline and decreases hepatic steatosis in long-term total parenteral nutrition patients. JPEN J Parenter Enteral Nutr 16: 487-488.
30. Ding, X., Saxena, N.K., Lin, S., Gupta, N.A. and Anania, F.A. ( 2006) Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology 43: 173-181.
31. Dixon, J.B., Bhathal, P.S., Hughes, N.R. and O'Brien, P.E. ( 2004) Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss. Hepatology 39: 1647-1654.
32. Dixon, J.B., Bhathal, P.S. and O'Brien, P.E. ( 2006) Weight loss and non-alcoholic fatty liver disease: falls in gamma-glutamyl transferase concentrations are associated with histologic improvement. Obes Surg 16: 1278-1286.
33. Donati, G., Stagni, B., Piscaglia, F., Venturoli, N., Morselli-Labate, A.M., Rasciti, L. et al (2004) Increased prevalence of fatty liver in arterial hypertensive patients with normal liver enzymes: role of insulin resistance. Gut 53: 1020-1023.
34. Dowman, J.K., Tomlinson, J.W. and Newsome, P.N. (2010) Pathogenesis of non-alcoholic fatty liver disease. QJM 103: 71-83.
35. Drucker, D.J. and Nauck, M.A. ( 2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368: 1696-1705.
36. Dufour, J.F., Oneta, C.M., Gonvers, J.J., Bihl, F., Cerny, A., Cereda, J.M. et al (2006) Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 4: 1537-1543.
37. Duseja, A., Murlidharan, R., Bhansali, A., Sharma, S., Das, A., Das, R. et al (2004) Assessment of insulin resistance and effect of metformin in nonalcoholic steatohepatitis-a preliminary report. Indian J Gastroenterol 23: 12-15.
38. Ekstedt, M., Franzen, L.E., Mathiesen, U.L., Thorelius, L., Holmqvist, M., Bodemar, G. et al (2006) Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 44: 865-873.
39. Enjoji, M., Kotoh, K., Kato, M., Higuchi, N., Kohjima, M., Nakashima, M. et al (2008) Therapeutic effect of ARBs on insulin resistance and liver injury in patients with NAFLD and chronic hepatitis C: a pilot study. Int J Mol Med 22: 521-527.
40. Facchini, F.S., Hua, N.W. and Stoohs, R.A. ( 2002) Effect of iron depletion in carbohydrate-intolerant patients with clinical evidence of nonalcoholic fatty liver disease. Gastroenterology 122: 931-939.
41. Ferrannini, E., Buzzigoli, G., Bonadonna, R., Giorico, M.A., Oleggini, M., Graziadei, L. et al (1987) Insulin resistance in essential hypertension. N Engl J Med 317: 350-357.
42. Furuya Jr, C.K., de Oliveira, C.P., de Mello, E.S., Faintuch, J., Raskovski, A., Matsuda, M. et al (2007) Effects of bariatric surgery on nonalcoholic fatty liver disease: preliminary findings after 2 years. J Gastroenterol Hepatol 22: 510-514.
43. Georgescu, E.F. ( 2008) Angiotensin receptor blockers in the treatment of NASH/NAFLD: could they be a first-class option? Adv Ther 25: 1141-1174.
44. Gerstein, H.C., Yusuf, S., Bosch, J., Pogue, J., Sheridan, P., Dinccag, N. et al (2006) Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 368: 1096-1105.
45. Gomez-Dominguez, E., Gisbert, J.P., Moreno-Monteagudo, J.A., Garcia-Buey, L. and Moreno-Otero, R. ( 2006) A pilot study of atorvastatin treatment in dyslipemid, non-alcoholic fatty liver patients. Aliment Pharmacol Ther 23: 1643-1647.
46. Grey, A., Bolland, M., Gamble, G., Wattie, D., Horne, A., Davidson, J. et al (2007) The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone decreases bone formation and bone mineral density in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab 92: 1305-1310.
47. Harrison, S.A., Fincke, C., Helinski, D., Torgerson, S. and Hayashi, P. ( 2004) A pilot study of orlistat treatment in obese, non-alcoholic steatohepatitis patients. Aliment Pharmacol Ther 20: 623-628.
48. Harrison, S.A., Torgerson, S., Hayashi, P., Ward, J. and Schenker, S. ( 2003) Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 98: 2485-2490.
49. Hussein, O., Grosovski, M., Schlesinger, S., Szvalb, S. and Assy, N. ( 2007) Orlistat reverse fatty infiltration and improves hepatic fibrosis in obese patients with nonalcoholic steatohepatitis (NASH). Dig Dis Sci 52: 2512-2519.
50. Jaskiewicz, K., Raczynska, S., Rzepko, R. and Sledzinski, Z. ( 2006) Nonalcoholic fatty liver disease treated by gastroplasty. Dig Dis Sci 51: 21-26.
51. Jou, J., Choi, S.S. and Diehl, A.M. ( 2008) Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis 28: 370-379.
52. Kechagias, S., Ernersson, A., Dahlqvist, O., Lundberg, P., Lindstrom, T. and Nystrom, F.H. ( 2008) Fast-food-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects. Gut 57: 649-654.
53. Keech, A., Simes, R.J., Barter, P., Best, J., Scott, R., Taskinen, M.R. et al (2005) Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 366: 1849-1861.
54. Kim, S.H., Lee, Y.M., Jee, S.H. and Nam, C.M. ( 2003) Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials. Obes Res 11: 1116-1123.
55. Knowler, W.C., Barrett-Connor, E., Fowler, S.E., Hamman, R.F., Lachin, J.M., Walker, E.A. et al (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346: 393-403.
56. Kotronen, A. and Yki-Jarvinen, H. ( 2008) Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol 28: 27-38.
57. Kugelmas, M., Hill, D.B., Vivian, B., Marsano, L. and McClain, C.J. ( 2003) Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. Hepatology 38: 413-419.
58. Lago, R.M., Singh, P.P. and Nesto, R.W. ( 2007) Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials. Lancet 370: 1129-1136.
59. Laurin, J., Lindor, K.D., Crippin, J.S., Gossard, A., Gores, G.J., Ludwig, J. et al (1996) Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: a pilot study. Hepatology 23: 1464-1467.
60. Levy, J.R., Clore, J.N. and Stevens, W. ( 2004) Dietary n-3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats. Hepatology 39: 608-616.
61. Lindor, K.D., Kowdley, K.V., Heathcote, E.J., Harrison, M.E., Jorgensen, R., Angulo, P. et al (2004) Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 39: 770-778.
62. Liu, X., Lazenby, A.J., Clements, R.H., Jhala, N. and Abrams, G.A. ( 2007) Resolution of nonalcoholic steatohepatits after gastric bypass surgery. Obes Surg 17: 486-492.
63. Loguercio, C., Federico, A., Tuccillo, C., Terracciano, F., D'Auria, M.V., de Simone, C. et al (2005) Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases. J Clin Gastroenterol 39: 540-543.
64. Lutchman, G., Modi, A., Kleiner, D.E., Promrat, K., Heller, T., Ghany, M. et al (2007) The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology 46: 424-429.
65. Luyckx, F.H., Desaive, C., Thiry, A., Dewe, W., Scheen, A.J., Gielen, J.E. et al (1998) Liver abnormalities in severely obese subjects: effect of drastic weight loss after gastroplasty. Int J Obes Relat Metab Disord 22: 222-226.
66. Machado, M., Marques-Vidal, P. and Cortez-Pinto, H. ( 2006) Hepatic histology in obese patients undergoing bariatric surgery. J Hepatol 45: 600-606.
67. Marchesini, G., Brizi, M., Bianchi, G., Tomassetti, S., Bugianesi, E., Lenzi, M. et al (2001 a) Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 50: 1844-1850.
68. Marchesini, G., Brizi, M., Bianchi, G., Tomassetti, S., Zoli, M. and Melchionda, N. ( 2001b) Metformin in non-alcoholic steatohepatitis. Lancet 358: 893-894.
69. Marchesini, G., Ridolfi, V. and Nepoti, V. ( 2008) Hepatotoxicity of fast food? Gut 57: 568-570.
70. McCullough, A.J. ( 2006) Pathophysiology of nonalcoholic steatohepatitis. J Clin Gastroenterol 40(3 Suppl 1): S17-S29.
71. Mehta, S.R., Thomas, E.L., Bell, J.D., Johnston, D.G. and Taylor-Robinson, S.D. ( 2008) Non-invasive means of measuring hepatic fat content. World J Gastroenterol 14: 3476-3483.
72. Morita, Y., Ueno, T., Sasaki, N., Tateishi, Y., Nagata, E., Kage, M. et al (2005) Nateglinide is useful for nonalcoholic steatohepatitis (NASH) patients with type 2 diabetes. Hepatogastroenterology 52: 1338-1343.
73. Musso, G., Gambino, R., de Michieli, F., Cassader, M., Rizzetto, M., Durazzo, M. et al (2003) Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 37: 909-916.
74. Nair, S., Diehl, A.M., Wiseman, M., Farr Jr, G.H. and Perrillo, R.P. ( 2004) Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther 20: 23-28.
75. Nakano, H., Nagasaki, H., Barama, A., Boudjema, K., Jaeck, D., Kumada, K. et al (1997) The effects of N-acetylcysteine and anti-intercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by a choline-methionine-deficient diet. Hepatology 26: 670-678.
76. Natali, A. and Ferrannini, E. ( 2006) Effects of metformin and thiazolidinediones on suppression of hepatic glucose production and stimulation of glucose uptake in type 2 diabetes: a systematic review. Diabetologia 49: 434-441.
77. Neuschwander-Tetri, B.A. ( 2001) Betaine: an old therapy for a new scourge. Am J Gastroenterol 96: 2534-2536.
78. Neuschwander-Tetri, B.A., Brunt, E.M., Wehmeier, K.R., Oliver, D. and Bacon, B.R. ( 2003) Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology 38: 1008-1017.
79. Nissen, S.E. and Wolski, K. ( 2007) Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 356: 2457-2471.
80. Padwal, R., Li, S.K. and Lau, D.C. ( 2004) Long-term pharmacotherapy for obesity and overweight. Cochrane Database Syst Rev 3: CD004094.
81. Petersen, K.F., Dufour, S., Befroy, D., Lehrke, M., Hendler, R.E. and Shulman, G.I. ( 2005) Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 54: 603-608.
82. Preiss, D. and Sattar, N. ( 2008) Non-alcoholic fatty liver disease: an overview of prevalence, diagnosis, pathogenesis and treatment considerations. Clin Sci (Lond) 115: 141-150.
83. Promrat, K., Kleiner, D.E., Niemeier, H.M., Jackvony, E., Kearns, M., Wands, J.R. et al (2010) Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 51: 121-129.
84. Promrat, K., Lutchman, G., Uwaifo, G.I., Freedman, R.J., Soza, A., Heller, T. et al (2004) A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology 39: 188-196.
85. Rallidis, L.S., Drakoulis, C.K. and Parasi, A.S. ( 2004) Pravastatin in patients with nonalcoholic steatohepatitis: results of a pilot study. Atherosclerosis 174: 193-196.
86. Ranlov, I. and Hardt, F. ( 1990) Regression of liver steatosis following gastroplasty or gastric bypass for morbid obesity. Digestion 47: 208-214.
87. Ratziu, V., Giral, P., Jacqueminet, S., Charlotte, F., Hartemann-Heurtier, A., Serfaty, L. et al (2008) Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology 135: 100-110.
88. Reddy, J.K. ( 2001) Nonalcoholic steatosis and steatohepatitis. III. Peroxisomal beta-oxidation, PPAR alpha, and steatohepatitis. Am J Physiol Gastrointest Liver Physiol 281: G1333-G1339.
89. Ruhl, C.E. and Everhart, J.E. ( 2003) Relation of elevated serum alanine aminotransferase activity with iron and antioxidant levels in the United States. Gastroenterology 124: 1821-1829.
90. Sabuncu, T., Nazligul, Y., Karaoglanoglu, M., Ucar, E. and Kilic, F.B. ( 2003) 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 12: 189-192.
91. Sanyal, A.J., Chalasani, N., Kowdley, K.V., McCullough, A., Diehl, A.M., Bass, N.M. et al (2010) Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 362: 1675-1685.
92. Sanyal, A.J., Mofrad, P.S., Contos, M.J., Sargeant, C., Luketic, V.A., Sterling, R.K. et al (2004) A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 2: 1107-1115.
93. Saris, W.H., Blair, S.N., van Baak, M.A., Eaton, S.B., Davies, P.S., Di Pietro, L. et al (2003) How much physical activity is enough to prevent unhealthy weight gain? Outcome of the IASO 1st Stock Conference and consensus statement. Obes Rev 4: 101-114.
94. Satapathy, S.K., Garg, S., Chauhan, R., Sakhuja, P., Malhotra, V., Sharma, B.C. et al (2004) Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. Am J Gastroenterol 99: 1946-1952.
95. Satapathy, S.K., Sakhuja, P., Malhotra, V., Sharma, B.C. and Sarin, S.K. ( 2007) Beneficial effects of pentoxifylline on hepatic steatosis, fibrosis and necroinflammation in patients with non-alcoholic steatohepatitis. J Gastroenterol Hepatol 22: 634-638.
96. Scarpello, J.H. and Howlett, H.C. ( 2008) Metformin therapy and clinical uses. Diab Vasc Dis Res 5: 157-167.
97. Schwimmer, J.B., Middleton, M.S., Deutsch, R. and Lavine, J.E. ( 2005) A phase 2 clinical trial of metformin as a treatment for non-diabetic paediatric non-alcoholic steatohepatitis. Aliment Pharmacol Ther 21: 871-879.
98. Solga, S., Alkhuraishe, A.R., Clark, J.M., Torbenson, M., Greenwald, A., Diehl, A.M. et al (2004) Dietary composition and nonalcoholic fatty liver disease. Dig Dis Sci 49: 1578-1583.
99. Stratopoulos, C., Papakonstantinou, A., Terzis, I., Spiliadi, C., Dimitriades, G., Komesidou, V. et al (2005) Changes in liver histology accompanying massive weight loss after gastroplasty for morbid obesity. Obes Surg 15: 1154-1160.
100. Targher, G., Bellis, A., Fornengo, P., Ciaravella, F., Pichiri, I., Cavallo Perin, P. et al (2010) Prevention and treatment of nonalcoholic fatty liver disease. Dig Liver Dis 42: 331-340.
101. Targher, G., Bertolini, L., Padovani, R., Rodella, S., Tessari, R., Zenari, L. et al (2007) Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 30: 1212-1218.
102. Targher, G., Marra, F. and Marchesini, G. ( 2008) Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon? Diabetologia 51: 1947-1953.
103. Tiikkainen, M., Hakkinen, A.M., Korsheninnikova, E., Nyman, T., Makimattila, S. and Yki-Jarvinen, H. ( 2004) 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 53: 2169-2176.
104. Uygun, A., Kadayifci, A., Isik, A.T., Ozgurtas, T., Deveci, S., Tuzun, A. et al (2004) Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 19: 537-544.
105. Valenti, L., Fracanzani, A.L. and Fargion, S. ( 2003) Effect of iron depletion in patients with nonalcoholic fatty liver disease without carbohydrate intolerance. Gastroenterology 124: 866, author reply 866-867.
106. Velayudham, A., Dolganiuc, A., Ellis, M., Petrasek, J., Kodys, K., Mandrekar, P. et al (2009) VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatology 49: 989-997.
107. Westerbacka, J., Lammi, K., Hakkinen, A.M., Rissanen, A., Salminen, I., Aro, A. et al (2005) Dietary fat content modifies liver fat in overweight nondiabetic subjects. J Clin Endocrinol Metab 90: 2804-2809.
108. Williams, G. ( 2010) Withdrawal of sibutramine in Europe. BMJ 340: c824.
109. Yki-Jarvinen, H. ( 2004) Thiazolidinediones. N Engl J Med 351: 1106-1118.
110. Yokohama, S., Yoneda, M., Haneda, M., Okamoto, S., Okada, M., Aso, K. et al (2004) Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology 40: 1222-1225.
111. Zambon, A. and Cusi, K. ( 2007) The role of fenofibrate in clinical practice. Diab Vasc Dis Res 4(Suppl 3): S15-S20.
112. Zelber-Sagi, S., Kessler, A., Brazowsky, E., Webb, M., Lurie, Y., Santo, M. et al (2006) A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 4: 639-644.
113. Zelber-Sagi, S., Nitzan-Kaluski, D., Goldsmith, R., Webb, M., Blendis, L., Halpern, Z. et al (2007) Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): a population based study. J Hepatol 47: 711-717.
114. Zhu, F.S., Liu, S., Chen, X.M., Huang, Z.G. and Zhang, D.W. ( 2008) Effects of n-3 polyunsaturated fatty acids from seal oils on nonalcoholic fatty liver disease associated with hyperlipidemia. World J Gastroenterol 14: 6395-6400.