Management of nonalcoholic steatohepatitis. An evidence-based approach

Clinics in Liver Disease

Volumn 16, Issue 3, 2012, Pages 631-645

  Mahady, Suzanne E ^a,b   George, Jacob ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

^b UNIVERSITY OF SYDNEY   (Australia)

Author keywords

Diet; Exercise; Fatty liver; Nonalcoholic steatohepatitis; Therapy

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ACETYLCYSTEINE; ALPHA TOCOPHEROL; ASCORBIC ACID; BETAINE; FRUCTOSE; GEMFIBROZIL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INSULIN SENSITIZING AGENT; METFORMIN; OMEGA 3 FATTY ACID; PROBUCOL; ROSIGLITAZONE; URSODEOXYCHOLIC ACID;

BARIATRIC SURGERY; BEHAVIOR THERAPY; CARDIOVASCULAR DISEASE; CLINICAL PRACTICE; COGNITIVE THERAPY; CONTROLLED CLINICAL TRIAL (TOPIC); DIETARY INTAKE; EVIDENCE BASED MEDICINE; EXERCISE; FRACTURE; HUMAN; INSULIN RESISTANCE; LIFESTYLE MODIFICATION; LIVER CELL CARCINOMA; MEDITERRANEAN DIET; NONALCOHOLIC FATTY LIVER; OSTEOLYSIS; PREVALENCE; REVIEW; SIDE EFFECT; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT; VIRUS HEPATITIS; WEIGHT REDUCTION;

ANTI-OBESITY AGENTS; BARIATRIC SURGERY; COGNITIVE THERAPY; DIET, MEDITERRANEAN; EVIDENCE-BASED MEDICINE; EXERCISE THERAPY; FATTY ACIDS, OMEGA-3; FATTY LIVER; HUMANS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RISK REDUCTION BEHAVIOR; TREATMENT OUTCOME;

EID: 84864110034     PISSN: 10893261     EISSN: 15578224     Source Type: Journal    
DOI: 10.1016/j.cld.2012.05.003     Document Type: Review

References (114)

1. Charlton M.R., Burns J.M., Pedersen R.A., et al. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology 2011, 141:1249-1253.
2. Targher G., Day C.P., Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 2010, 363:1341-1350.
3. Atkins D., Best D., Briss P.A., et al. Grading quality of evidence and strength of recommendations. BMJ 2004, 328:1490.
4. Sanyal A.J. AGA technical review on nonalcoholic fatty liver disease. Gastroenterology 2002, 123:1705-1725.
5. 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, 53:372-384.
6. Farrell G.C., Chitturi S., Lau G.K., et al. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary. J Gastroenterol Hepatol 2007, 22:775-777.
7. Sanyal A.J., Brunt E.M., Kleiner D.E., et al. Endpoints and clinical trial design for nonalcoholic steatohepatitis. Hepatology 2011, 54:344-353.
8. Tuomilehto J., Lindstrom J., Eriksson J.G., et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001, 344:1343-1350.
9. Knowler W.C., Barrett-Connor E., Fowler S.E., et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002, 346:393-403.
10. Ramachandran A., Snehalatha C., Mary S., et al. The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia 2006, 49:289-297.
11. Lindstrom J., Ilanne-Parikka P., Peltonen M., et al. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet 2006, 368:1673-1679.
12. Kosaka K., Noda M., Kuzuya T. Prevention of type 2 diabetes by lifestyle intervention: a Japanese trial in IGT males. Diabetes Res Clin Pract 2005, 67:152-162.
13. Laaksonen D.E., Lindstrom J., Lakka T.A., et al. Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study. Diabetes 2005, 54:158-165.
14. Sesso H.D., Paffenbarger R.S., Lee I.M. Physical activity and coronary heart disease in men: the Harvard Alumni Health Study. Circulation 2000, 102:975-980.
15. Wei M., Kampert J.B., Barlow C.E., et al. Relationship between low cardiorespiratory fitness and mortality in normal-weight, overweight, and obese men. JAMA 1999, 282:1547-1553.
16. Promrat K., Kleiner D.E., Niemeier H.M., et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010, 51:121-129.
17. Vilar Gomez E., Rodriguez De Miranda A., Gra Oramas B., et al. 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.
18. Lazo M., Solga S.F., Horska A., et al. Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with type 2 diabetes. Diabetes Care 2010, 33:2156-2163.
19. St George A., Bauman A., Johnston A., et al. Effect of a lifestyle intervention in patients with abnormal liver enzymes and metabolic risk factors. J Gastroenterol Hepatol 2009, 24:399-407.
20. Sreenivasa Baba C., Alexander G., Kalyani B., et al. Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis. J Gastroenterol Hepatol 2006, 21:191-198.
21. Thoma C., Day C.P., Trenell M.I. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol 2012, 56(1):255-266. [Epub 2011 Jul 1]. 10.1016/j.jhep.2011.06.010.
22. St George A., Bauman A., Johnston A., et al. Independent effects of physical activity in patients with nonalcoholic fatty liver disease. Hepatology 2009, 50:68-76.
23. Zivkovic A.M., German J.B., Sanyal A.J. Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease. Am J Clin Nutr 2007, 86:285-300.
24. Sacks F.M., Bray G.A., Carey V.J., et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009, 360:859-873.
25. Andersen T., Gluud C., Franzmann M.B., et al. Hepatic effects of dietary weight loss in morbidly obese subjects. J Hepatol 1991, 12:224-229.
26. Rozental P., Biava C., Spencer H., et al. Liver morphology and function tests in obesity and during total starvation. Am J Dig Dis 1967, 12:198-208.
27. Capron J.P., Delamarre J., Dupas J.L., et al. Fasting in obesity: another cause of liver injury with alcoholic hyaline?. Dig Dis Sci 1982, 27:265-268.
28. Xu J., Cho H., O'Malley S., et al. Dietary polyunsaturated fats regulate rat liver sterol regulatory element binding proteins-1 and -2 in three distinct stages and by different mechanisms. J Nutr 2002, 132:3333-3339.
29. Musso G., Gambino R., De Michieli F., et al. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 2003, 37:909-916.
30. Cortez-Pinto H., Jesus L., Barros H., et al. How different is the dietary pattern in non-alcoholic steatohepatitis patients?. Clin Nutr 2006, 25:816-823.
31. Simopoulos A.P. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 2002, 56:365-379.
32. 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, 47:711-717.
33. Levy J.R., Clore J.N., Stevens W. Dietary n-3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats. Hepatology 2004, 39:608-616.
34. Sekiya M., Yahagi N., Matsuzaka T., et al. Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology 2003, 38:1529-1539.
35. Capanni M., Calella F., Biagini M.R., et al. Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study. Aliment Pharmacol Ther 2006, 23:1143-1151.
36. Zhu F.S., Liu S., Chen X.M., et al. Effects of n-3 polyunsaturated fatty acids from seal oils on nonalcoholic fatty liver disease associated with hyperlipidemia. World J Gastroenterol 2008, 14:6395-6400.
37. Spadaro L., Magliocco O., Spampinato D., et al. Effects of n-3 polyunsaturated fatty acids in subjects with nonalcoholic fatty liver disease. Dig Liver Dis 2008, 40:194-199.
38. Parker H.M., Johnson N.A., Burdon C.A., et al. Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta analysis. J Hepatol 2011, 10.1016/j.jhep.2011.08.018.
39. Ryan M.C., Itsiopoulos C., Ward G., et al. The Mediterranean diet: improvement in hepatic steatosis and insulin sensitivity in individuals with NAFLD. Hepatology 2011, 54(Suppl 4):212A.
40. Canberra: National Health and Medical Research Council. Department of Health; 2005. Available at: Accessed February, 2012. http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/n31.pdf.
41. Shai I., Schwarzfuchs D., Henkin Y., et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med 2008, 359:229-241.
42. Ouyang X., Cirillo P., Sautin Y., et al. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol 2008, 48:993-999.
43. Elliott S.S., Keim N.L., Stern J.S., et al. Fructose, weight gain, and the insulin resistance syndrome. Am J Clin Nutr 2002, 76:911-922.
44. Fields M., Lewis C.G., Lure M.D. Responses of insulin to oral glucose and fructose loads in marginally copper-deficient rats fed starch or fructose. Nutrition 1996, 12:524-528.
45. Martinez F.J., Rizza R.A., Romero J.C. High-fructose feeding elicits insulin resistance, hyperinsulinism, and hypertension in normal mongrel dogs. Hypertension 1994, 23:456-463.
46. Bhosale S.H., Rao M.B., Deshpande V.V. Molecular and industrial aspects of glucose isomerase. Microbiol Rev 1996, 60:280-300.
47. Bray G.A., Nielsen S.J., Popkin B.M. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 2004, 79:537-543.
48. Teff K.L., Elliott S.S., Tschop M., et al. Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J Clin Endocrinol Metab 2004, 89:2963-2972.
49. Shapiro A., Mu W., Roncal C., et al. Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding. Am J Physiol Regul Integr Comp Physiol 2008, 295:R1370-R1375.
50. Johnson N.A., Sachinwalla T., Walton D.W., et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology 2009, 50:1105-1112.
51. Finucane F.M., Sharp S.J., Purslow L.R., et al. The effects of aerobic exercise on metabolic risk, insulin sensitivity and intrahepatic lipid in healthy older people from the Hertfordshire Cohort Study: a randomised controlled trial. Diabetologia 2010, 53:624-631.
52. Pessayre D. Role of mitochondria in non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2007, 22(Suppl 1):S20-S27.
53. Petersen K.F., Dufour S., Befroy D., et al. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 2004, 350:664-671.
54. Skarfors E.T., Wegener T.A., Lithell H., et al. Physical training as treatment for type 2 (non-insulin-dependent) diabetes in elderly men. A feasibility study over 2 years. Diabetologia 1987, 30:930-933.
55. Eden K.B., Orleans C.T., Mulrow C.D., et al. Does counseling by clinicians improve physical activity? a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002, 137:208-215.
56. Fabricatore A.N. Behavior therapy and cognitive-behavioral therapy of obesity: is there a difference?. J Am Diet Assoc 2007, 107:92-99.
57. Moscatiello S., Di Luzio R., Bugianesi E., et al. Cognitive-behavioral treatment of nonalcoholic fatty liver disease: a propensity score-adjusted observational study. Obesity 2011, 19:763-770.
58. Bellentani S., Dalle Grave R., Suppini A., et al. Behavior therapy for nonalcoholic fatty liver disease: the need for a multidisciplinary approach. Hepatology 2008, 47:746-754.
59. Frith J., Day C.P., Robinson L., et al. Potential strategies to improve uptake of exercise interventions in non-alcoholic fatty liver disease. J Hepatol 2010, 52:112-116.
60. Kantartzis K., Thamer C., Peter A., et al. 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.
61. Palmer M., Schaffner F. Effect of weight reduction on hepatic abnormalities in overweight patients. Gastroenterology 1990, 99:1408-1413.
62. Albu J.B., Heilbronn L.K., Kelley D.E., et al. Metabolic changes following a 1-year diet and exercise intervention in patients with type 2 diabetes. Diabetes 2010, 59:627-633.
63. Marchesini G., Brizi M., Morselli-Labate A.M., et al. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 1999, 107:450-455.
64. Chitturi S., Abeygunasekera S., Farrell G.C., et al. NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology 2002, 35:373-379.
65. Yki-Jarvinen H. Thiazolidinediones. N Engl J Med 2004, 351:1106-1118.
66. Ialenti A., Grassia G., Di Meglio P., et al. Mechanism of the anti-inflammatory effect of thiazolidinediones: relationship with the glucocorticoid pathway. Mol Pharmacol 2005, 67:1620-1628.
67. Sidhu J.S., Kaposzta Z., Markus H.S., et al. Effect of rosiglitazone on common carotid intima-media thickness progression in coronary artery disease patients without diabetes mellitus. Arterioscler Thromb Vasc Biol 2004, 24:930-934.
68. Tonelli J., Li W., Kishore P., et al. Mechanisms of early insulin-sensitizing effects of thiazolidinediones in type 2 diabetes. Diabetes 2004, 53:1621-1629.
69. Belfort R., Harrison S.A., Brown K., et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006, 355:2297-2307.
70. Ratziu V., Giral P., Jacqueminet S., et al. 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.
71. Aithal G.P., Thomas J.A., Kaye P.V., et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology 2008, 135:1176-1184.
72. Sanyal A.J., Chalasani N., Kowdley K.V., et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010, 362:1675-1685.
73. Idilman R., Mizrak D., Corapcioglu D., et al. Clinical trial: insulin-sensitizing agents may reduce consequences of insulin resistance in individuals with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2008, 28:200-208.
74. Ratziu V., Charlotte F., Bernhardt C., et al. 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.
75. Mahady S.E., Walker S., Sanyal A., et al. The role of thiazolidinediones in non-alcoholic steatohepatitis-a systematic review and meta analysis. J Hepatol 2011, 55:1383-1390.
76. Singh S., Loke Y.K., Furberg C.D. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA 2007, 298:1189-1195.
77. Lincoff A.M., Wolski K., Nicholls S.J., et al. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA 2007, 298:1180-1188.
78. Murphy C.E., Rodgers P.T. Effects of thiazolidinediones on bone loss and fracture. Ann Pharmacother 2007, 41:2014-2018.
79. Schwartz A.V., Sellmeyer D.E., Vittinghoff E., et al. Thiazolidinedione use and bone loss in older diabetic adults. J Clin Endocrinol Metab 2006, 91:3349-3354.
80. Lewis J.D., Ferrara A., Peng T., et al. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care 2011, 34:916-922.
81. Pagadala M., Zein C.O. Predictors of steatohepatitis and advanced fibrosis in non-alcoholic fatty liver disease. Clin Liver Dis 2009, 13:591-606.
82. Durbin R.J. Thiazolidinedione therapy in the prevention/delay of type 2 diabetes in patients with impaired glucose tolerance and insulin resistance. Diabetes Obes Metab 2004, 6:280-285.
83. Gerstein H.C., Yusuf S., Bosch J., et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006, 368:1096-1105.
84. Parola M., Muraca R., Dianzani I., et al. Vitamin E dietary supplementation inhibits transforming growth factor beta 1 gene expression in the rat liver. FEBS Lett 1992, 308:267-270.
85. Houglum K., Venkataramani A., Lyche K., et al. A pilot study of the effects of d-alpha-tocopherol on hepatic stellate cell activation in chronic hepatitis C. Gastroenterology 1997, 113:1069-1073.
86. Nobili V., Manco M., Devito R., et al. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: a randomized, controlled trial. Hepatology 2008, 48:119-128.
87. 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, 100:1082-1090.
88. Miller E.R., Pastor-Barriuso R., Dalal D., et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005, 142:37-46.
89. Harrison S.A., Fecht W., Brunt E.M., et al. Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial. Hepatology 2009, 49:80-86.
90. Zelber-Sagi S., Kessler A., Brazowsky E., et al. A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2006, 4:639-644.
91. Omer Z., Cetinkalp S., Akyildiz M., et al. Efficacy of insulin sensitizing agents in nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2010, 22:18-23.
92. Lindor K.D., Kowdley K.V., Heathcote E.J., et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 2004, 39:770-778.
93. Dufour J.F., Oneta C.M., Gonvers J.J., et al. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin E in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 2006, 4:1537-1543.
94. Santos V.N., Lanzoni V.P., 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, 36:723-729.
95. Nelson A., Torres D.M., Morgan A.E., et al. A pilot study using simvastatin in the treatment of nonalcoholic steatohepatitis: a randomized placebo-controlled trial. J Clin Gastroenterol 2009, 43:990-994.
96. Basaranoglu M., Acbay O., Sonsuz A. A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis. J Hepatol 1999, 31:384.
97. Merat S., Malekzadeh R., Sohrabi M.R., et al. Probucol in the treatment of non-alcoholic steatohepatitis: a double-blind randomized controlled study. J Hepatol 2003, 38:414-418.
98. Harrison S.A., Torgerson S., Hayashi P., et al. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2003, 98:2485-2490.
99. Abdelmalek M.F., Sanderson S.O., Angulo P., et al. Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial. Hepatology 2009, 50:1818-1826.
100. Pamuk G.E., Sonsuz A. N-acetylcysteine in the treatment of non-alcoholic steatohepatitis. J Gastroenterol Hepatol 2003, 18:1220-1221.
101. Livingston E.H. Procedure incidence and in-hospital complication rates of bariatric surgery in the United States. Am J Surg 2004, 188:105-110.
102. NIH conference. Gastrointestinal surgery for severe obesity. Consensus development conference panel. Ann Intern Med 1991, 115:956-961.
103. Dixon J.B., Bhathal P.S., Hughes N.R., et al. Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss. Hepatology 2004, 39:1647-1654.
104. Kral J.G., Thung S.N., Biron S., et al. Effects of surgical treatment of the metabolic syndrome on liver fibrosis and cirrhosis. Surgery 2004, 135:48-58.
105. Klein S., Mittendorfer B., Eagon J.C., et al. Gastric bypass surgery improves metabolic and hepatic abnormalities associated with nonalcoholic fatty liver disease. Gastroenterology 2006, 130:1564-1572.
106. Mathurin P., Hollebecque A., Arnalsteen L., et al. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology 2009, 137:532-540.
107. Mummadi R.R., Kasturi K.S., Chennareddygari S., et al. Effect of bariatric surgery on nonalcoholic fatty liver disease: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2008, 6:1396-1402.
108. O'Brien P.E., Dixon J.B., Brown W. Obesity is a surgical disease: overview of obesity and bariatric surgery. ANZ J Surg 2004, 74:200-204.
109. O'Brien P.E., Brown W.A., Dixon J.B. Obesity, weight loss and bariatric surgery. Med J Aust 2005, 183:310-314.
110. Buchwald H., Avidor Y., Braunwald E., et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004, 292:1724-1737.
111. Angulo P. NAFLD, obesity, and bariatric surgery. Gastroenterology 2006, 130:1848-1852.
112. Cotler S.J., Vitello J.M., Guzman G., et al. Hepatic decompensation after gastric bypass surgery for severe obesity. Dig Dis Sci 2004, 49:1563-1568.
113. Tilg H., Moschen A.R. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 2010, 52:1836-1846.
114. Musso G., Gambino R., Cassader M. Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded?. Diabetes Care 2010, 33:2277-2284.