Treatment of NAFLD with diet, physical activity and exercise

Journal of Hepatology

Volumn 67, Issue 4, 2017, Pages 829-846

  Romero Gómez, Manuel ^a   Zelber Sagi, Shira ^b,c   Trenell, Michael ^d  

^a HOSPITAL UNIVERSITARIO VIRGEN DEL ROCÍO   (Spain)

^b TEL AVIV SOURASKY MEDICAL CENTER   (Israel)

^c UNIVERSITY OF HAIFA   (Israel)

^d NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

Behaviour intervention; Exercise; Fibrosis; Mediterranean diet; Physical activity; Steatohepatitis; Steatosis; Weight loss

Indexed keywords

CARBOHYDRATE; OMEGA 3 FATTY ACID; TRACE ELEMENT;

BEHAVIOR CHANGE; BEHAVIOR THERAPY; CALORIE; CANCER RISK; DIET THERAPY; EXERCISE; FOOD COMPOSITION; HUMAN; LIFESTYLE MODIFICATION; LIVER CELL CARCINOMA; MACRONUTRIENT; MEDITERRANEAN DIET; NONALCOHOLIC FATTY LIVER; NONALCOHOLIC FATTY LIVER DISEASE ACTIVITY SCORE; PHYSICAL ACTIVITY; PRIORITY JOURNAL; PROPHYLAXIS; RELAPSE; REVIEW; RISK REDUCTION; SEDENTARY LIFESTYLE; WEIGHT REDUCTION; BODY WEIGHT LOSS; CALORIC RESTRICTION; CLINICAL TRIAL (TOPIC); LIFESTYLE; LIVER TUMOR; RISK FACTOR;

BEHAVIOR THERAPY; CALORIC RESTRICTION; CARCINOMA, HEPATOCELLULAR; CLINICAL TRIALS AS TOPIC; DIET, MEDITERRANEAN; EXERCISE; HUMANS; LIFE STYLE; LIVER NEOPLASMS; MICRONUTRIENTS; NON-ALCOHOLIC FATTY LIVER DISEASE; RISK FACTORS; RISK REDUCTION BEHAVIOR; SEDENTARY LIFESTYLE; WEIGHT LOSS;

EID: 85021683483     PISSN: 01688278     EISSN: 16000641     Source Type: Journal    
DOI: 10.1016/j.jhep.2017.05.016     Document Type: Review

References (191)

1. Chalasani, N., Younossi, Z., Lavine, J.E., Diehl, A.M., Brunt, E.M., Cusi, K., et al. 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 55 (2012), 2005–2023.
2. Farrell, G.C., van Rooyen, D., Gan, L., Chitturi, S., NASH is an inflammatory disorder: pathogenic, prognostic and therapeutic implications. Gut Liver 6 (2012), 149–171.
3. Vernon, G., Baranova, A., Younossi, Z.M., Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34 (2011), 274–285.
4. Charlton, M.R., Burns, J.M., Pedersen, R.A., Watt, K.D., Heimbach, J.K., Dierkhising, R.A., Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology 141 (2011), 1249–1253.
5. Shaker, M., Tabbaa, A., Albeldawi, M., Alkhouri, N., Liver transplantation for nonalcoholic fatty liver disease: new challenges and new opportunities. World J Gastroenterol 20 (2014), 5320–5330.
6. Shen, J., Wong, G.L., Chan, H.L., Chan, H.Y., Yeung, D.K., Chan, R.S., et al. PNPLA3 gene polymorphism accounts for fatty liver in community subjects without metabolic syndrome. Aliment Pharmacol Ther 39 (2014), 532–539.
7. Wang, X., Liu, Z., Wang, K., Wang, Z., Sun, X., Zhong, L., et al. Additive effects of the risk alleles of PNPLA3 and TM6SF2 on non-alcoholic fatty liver disease (NAFLD) in a Chinese population. Front Genet, 7, 2016, 140.
8. Younossi, Z.M., Koenig, A.B., Abdelatif, D., Fazel, Y., Henry, L., Wymer, M., Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 64 (2016), 73–84.
9. Zelber-Sagi, S., Lotan, R., Shlomai, A., Webb, M., Harrari, G., Buch, A., et al. Predictors for incidence and remission of NAFLD in the general population during a seven-year prospective follow-up. J Hepatol 56 (2012), 1145–1151.
10. Koopman, K.E., Caan, M.W., Nederveen, A.J., Pels, A., Ackermans, M.T., Fliers, E., et al. Hypercaloric diets with increased meal frequency, but not meal size, increase intrahepatic triglycerides: a randomized controlled trial. Hepatology 60 (2014), 545–553.
11. Diabetes Obesity, EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 64 (2016), 1388–1402.
12. Vilar-Gomez, E., Martinez-Perez, Y., Calzadilla-Bertot, L., Torres-Gonzalez, A., Gra-Oramas, B., Gonzalez-Fabian, L., et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology 149 (2015), 367–378 [Quiz e314–e365].
13. Storlien, L.H., Kraegen, E.W., Chisholm, D.J., Ford, G.L., Bruce, D.G., Pascoe, W.S., Fish oil prevents insulin resistance induced by high-fat feeding in rats. Science 237 (1987), 885–888.
14. Sekiya, M., Yahagi, N., Matsuzaka, T., Najima, Y., Nakakuki, M., Nagai, R., et al. Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Hepatology 38 (2003), 1529–1539.
15. Levy, J.R., Clore, J.N., Stevens, W., Dietary n-3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats. Hepatology 39 (2004), 608–616.
16. Musso, G., Gambino, R., De Michieli, F., Cassader, M., Rizzetto, M., Durazzo, M., et al. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 37 (2003), 909–916.
17. Toshimitsu, K., Matsuura, B., Ohkubo, I., Niiya, T., Furukawa, S., Hiasa, Y., et al. Dietary habits and nutrient intake in non-alcoholic steatohepatitis. Nutrition 23 (2007), 46–52.
18. Cortez-Pinto, H., Jesus, L., Barros, H., Lopes, C., Moura, M.C., Camilo, M.E., How different is the dietary pattern in non-alcoholic steatohepatitis patients?. Clin Nutr 25 (2006), 816–823.
19. Zelber-Sagi, S., Nitzan-Kaluski, D., Goldsmith, R., Webb, M., Blendis, L., Halpern, Z., et al. Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): a population based study. J Hepatol 47 (2007), 711–717.
20. Rosqvist, F., Iggman, D., Kullberg, J., Cedernaes, J., Johansson, H.E., Larsson, A., et al. Overfeeding polyunsaturated and saturated fat causes distinct effects on liver and visceral fat accumulation in humans. Diabetes 63 (2014), 2356–2368.
21. Bjermo, H., Iggman, D., Kullberg, J., Dahlman, I., Johansson, L., Persson, L., et al. Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. Am J Clin Nutr 95 (2012), 1003–1012.
22. Parker, H.M., Johnson, N.A., Burdon, C.A., Cohn, J.S., O'Connor, H.T., George, J., Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 56 (2012), 944–951.
23. Lu, W., Li, S., Li, J., Wang, J., Zhang, R., Zhou, Y., et al. Effects of omega-3 fatty acid in nonalcoholic fatty liver disease: a meta-analysis. Gastroenterol Res Pract, 2016, 2016, 1459790.
24. Scorletti, E., Bhatia, L., McCormick, K.G., Clough, G.F., Nash, K., Hodson, L., et al. Effects of purified eicosapentaenoic and docosahexaenoic acids in non-alcoholic fatty liver disease: Results from the ∗WELCOME study. Hepatology 60:4 (2014), 1211–1221.
25. Sanyal, A.J., Abdelmalek, M.F., Suzuki, A., Cummings, O.W., Chojkier, M., EPE-A Study Group. No significant effects of ethyl-eicosapentanoic acid on histologic features of nonalcoholic steatohepatitis in a phase 2 trial. Gastroenterology 147 (2014), 377–384 e371.
26. Argo, C.K., Patrie, J.T., Lackner, C., Henry, T.D., de Lange, E.E., Weltman, A.L., et al. Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial. J Hepatol 62 (2015), 190–197.
27. Mensink, R.P., Zock, P.L., Kester, A.D., Katan, M.B., Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr 77 (2003), 1146–1155.
28. Garg, A., High-monounsaturated-fat diets for patients with diabetes mellitus: a meta-analysis. Am J Clin Nutr 67 (1998), 577S–582S.
29. Grosso, G., Mistretta, A., Frigiola, A., Gruttadauria, S., Biondi, A., Basile, F., et al. Mediterranean diet and cardiovascular risk factors: a systematic review. Crit Rev Food Sci Nutr 54 (2014), 593–610.
30. Estruch, R., Ros, E., Salas-Salvado, J., Covas, M.I., Corella, D., Aros, F., et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 368 (2013), 1279–1290.
31. Salas-Salvado, J., Bullo, M., Estruch, R., Ros, E., Covas, M.I., Ibarrola-Jurado, N., et al. Prevention of diabetes with Mediterranean diets: a subgroup analysis of a randomized trial. Ann Intern Med 160 (2014), 1–10.
32. Uribarri, J., Del Castillo, M.D., de la Maza, M.P., Filip, R., Gugliucci, A., Luevano-Contreras, C., et al. Dietary advanced glycation end products and their role in health and disease. Advances in nutrition 6 (2015), 461–473.
33. Kellow, N.J., Savige, G.S., Dietary advanced glycation end-product restriction for the attenuation of insulin resistance, oxidative stress and endothelial dysfunction: a systematic review. Eur J Clin Nutr 67 (2013), 239–248.
34. Singh, R., Barden, A., Mori, T., Beilin, L., Advanced glycation end-products: a review. Diabetologia 44 (2001), 129–146.
35. Koschinsky, T., He, C.J., Mitsuhashi, T., Bucala, R., Liu, C., Buenting, C., et al. Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc Natl Acad Sci USA 94 (1997), 6474–6479.
36. Ramasamy, R., Yan, S.F., Schmidt, A.M., Advanced glycation endproducts: from precursors to RAGE: round and round we go. Amino Acids 42 (2012), 1151–1161.
37. Goldberg, T., Cai, W., Peppa, M., Dardaine, V., Baliga, B.S., Uribarri, J., et al. Advanced glycoxidation end products in commonly consumed foods. J Am Diet Assoc 104 (2004), 1287–1291.
38. Uribarri, J., Woodruff, S., Goodman, S., Cai, W., Chen, X., Pyzik, R., et al. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc 110 (2010), 911–916 e912.
39. Hyogo, H., Yamagishi, S., Iwamoto, K., Arihiro, K., Takeuchi, M., Sato, T., et al. Elevated levels of serum advanced glycation end products in patients with non-alcoholic steatohepatitis. J Gastroenterol Hepatol 22 (2007), 1112–1119.
40. Schmidt, A.M., Soluble RAGEs – Prospects for treating & tracking metabolic and inflammatory disease. Vascul Pharmacol 72 (2015), 1–8.
41. Zelber-Sagi, S., Salomone, F., Kolodkin-Gal, I., Erez, N., Buch, A., Yeshua, H., et al. Protective role of soluble receptor for advanced glycation end-products in patients with non-alcoholic fatty liver disease. Dig Liver Dis 49 (2017), 523–529.
42. Trovato, F.M., Catalano, D., Martines, G.F., Pace, P., Trovato, G.M., Mediterranean diet and non-alcoholic fatty liver disease: the need of extended and comprehensive interventions. Clin Nutr 34 (2015), 86–88.
43. Bozzetto, L., Prinster, A., Annuzzi, G., Costagliola, L., Mangione, A., Vitelli, A., et al. Liver fat is reduced by an isoenergetic MUFA diet in a controlled randomized study in type 2 diabetic patients. Diabetes Care 35 (2012), 1429–1435.
44. Ryan, M.C., Itsiopoulos, C., Thodis, T., Ward, G., Trost, N., Hofferberth, S., et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol 59 (2013), 138–143.
45. Ascha, M.S., Hanouneh, I.A., Lopez, R., Tamimi, T.A., Feldstein, A.F., Zein, N.N., The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 51 (2010), 1972–1978.
46. Moriya, A., Iwasaki, Y., Ohguchi, S., Kayashima, E., Mitsumune, T., Taniguchi, H., et al. Roles of alcohol consumption in fatty liver: a longitudinal study. J Hepatol 62 (2015), 921–927.
47. Dunn, W., Xu, R., Schwimmer, J.B., Modest wine drinking and decreased prevalence of suspected nonalcoholic fatty liver disease. Hepatology 47 (2008), 1947–1954.
48. Dixon, J.B., Bhathal, P.S., O'Brien, P.E., Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 121 (2001), 91–100.
49. Kwon, H.K., Greenson, J.K., Conjeevaram, H.S., Effect of lifetime alcohol consumption on the histological severity of non-alcoholic fatty liver disease. Liver Int 34 (2014), 129–135.
50. Hashimoto, Y., Hamaguchi, M., Kojima, T., Ohshima, Y., Ohbora, A., Kato, T., et al. Modest alcohol consumption reduces the incidence of fatty liver in men: a population-based large-scale cohort study. J Gastroenterol Hepatol 30 (2015), 546–552.
51. Dunn, W., Sanyal, A.J., Brunt, E.M., Unalp-Arida, A., Donohue, M., McCullough, A.J., et al. Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD). J Hepatol 57 (2012), 384–391.
52. Howard, B.V., Wylie-Rosett, J., Sugar and cardiovascular disease: A statement for healthcare professionals from the Committee on Nutrition of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association. Circulation 106 (2002), 523–527.
53. Ouyang, X., Cirillo, P., Sautin, Y., McCall, S., Bruchette, J.L., Diehl, A.M., et al. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol 48 (2008), 993–999.
54. Assy, N., Nasser, G., Kamayse, I., Nseir, W., Beniashvili, Z., Djibre, A., et al. Soft drink consumption linked with fatty liver in the absence of traditional risk factors. Can J Gastroenterol 22 (2008), 811–816.
55. Abid, A., Taha, O., Nseir, W., Farah, R., Grosovski, M., Assy, N., Soft drink consumption is associated with fatty liver disease independent of metabolic syndrome. J Hepatol 51 (2009), 918–924.
56. Poulsom, R., Morphological changes of organs after sucrose or fructose feeding. Prog Biochem Pharmacol 21 (1986), 104–134.
57. Herman, R.H., Zakim, D., Stifel, F.B., Effect of diet on lipid metabolism in experimental animals and man. Fed Proc 29 (1970), 1302–1307.
58. Vos, M.B., McClain, C.J., Fructose takes a toll. Hepatology 50 (2009), 1004–1006.
59. Bergheim, I., Weber, S., Vos, M., Kramer, S., Volynets, V., Kaserouni, S., et al. Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. J Hepatol 48 (2008), 983–992.
60. Vos, M.B., Lavine, J.E., Dietary fructose in nonalcoholic fatty liver disease. Hepatology 57 (2013), 2525–2531.
61. Choi, J.W., Ford, E.S., Gao, X., Choi, H.K., Sugar-sweetened soft drinks, diet soft drinks, and serum uric acid level: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 59 (2008), 109–116.
62. Afzali, A., Weiss, N.S., Boyko, E.J., Ioannou, G.N., Association between serum uric acid level and chronic liver disease in the United States. Hepatology 52 (2010), 578–589.
63. Xu, C., Yu, C., Xu, L., Miao, M., Li, Y., High serum uric acid increases the risk for nonalcoholic Fatty liver disease: a prospective observational study. PLoS One, 5, 2010, e11578.
64. Zelber-Sagi, S., Ben-Assuli, O., Rabinowich, L., Goldstein, A., Magid, A., Shalev, V., et al. The association between the serum levels of uric acid and alanine aminotransferase in a population-based cohort. Liver Int 59 (2015), 109–116.
65. Leung, C., Herath, C.B., Jia, Z., Goodwin, M., Mak, K.Y., Watt, M.J., et al. Dietary glycotoxins exacerbate progression of experimental fatty liver disease. J Hepatol 60 (2014), 832–838.
66. Ma, J., Fox, C.S., Jacques, P.F., Speliotes, E.K., Hoffmann, U., Smith, C.E., et al. Sugar-sweetened beverage, diet soda, and fatty liver disease in the Framingham Heart Study cohorts. J Hepatol 63 (2015), 462–469.
67. Maersk, M., Belza, A., Stodkilde-Jorgensen, H., Ringgaard, S., Chabanova, E., Thomsen, H., et al. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Am J Clin Nutr 95 (2012), 283–289.
68. Abdelmalek, M.F., Suzuki, A., Guy, C., Unalp-Arida, A., Colvin, R., Johnson, R.J., et al. Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease. Hepatology 51 (2010), 1961–1971.
69. Sawada, N., Inoue, M., Iwasaki, M., Sasazuki, S., Shimazu, T., Yamaji, T., et al. Consumption of n-3 fatty acids and fish reduces risk of hepatocellular carcinoma. Gastroenterology 142 (2012), 1468–1475.
70. Ioannou, G.N., Morrow, O.B., Connole, M.L., Lee, S.P., Association between dietary nutrient composition and the incidence of cirrhosis or liver cancer in the United States population. Hepatology 50 (2009), 175–184.
71. Fedirko, V., Lukanova, A., Bamia, C., Trichopolou, A., Trepo, E., Nothlings, U., et al. Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans. Ann Oncol 24 (2013), 543–553.
72. Yang, Y., Zhang, D., Feng, N., Chen, G., Liu, J., Chen, G., et al. Increased intake of vegetables, but not fruit, reduces risk for hepatocellular carcinoma: a meta-analysis. Gastroenterology 147 (2014), 1031–1042.
73. Turati, F., Trichopoulos, D., Polesel, J., Bravi, F., Rossi, M., Talamini, R., et al. Mediterranean diet and hepatocellular carcinoma. J Hepatol 60 (2014), 606–611.
74. Vitaglione, P., Morisco, F., Mazzone, G., Amoruso, D.C., Ribecco, M.T., Romano, A., et al. Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins. Hepatology 52 (2010), 1652–1661.
75. Salomone, F., Li Volti, G., Vitaglione, P., Morisco, F., Fogliano, V., Zappala, A., et al. Coffee enhances the expression of chaperones and antioxidant proteins in rats with nonalcoholic fatty liver disease. Transl Res 163 (2013), 593–602.
76. Shi, H., Dong, L., Dang, X., Liu, Y., Jiang, J., Wang, Y., et al. Effect of chlorogenic acid on LPS-induced proinflammatory signaling in hepatic stellate cells. Inflamm Res 62 (2013), 581–587.
77. Shang, F., Li, X., Jiang, X., Coffee consumption and risk of the metabolic syndrome: A meta-analysis. Diabetes Metab 42 (2016), 80–87.
78. Ding, M., Bhupathiraju, S.N., Chen, M., van Dam, R.M., Hu, F.B., Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: a systematic review and a dose-response meta-analysis. Diabetes Care 37 (2014), 569–586.
79. Molloy, J.W., Calcagno, C.J., Williams, C.D., Jones, F.J., Torres, D.M., Harrison, S.A., Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis. Hepatology 55 (2012), 429–436.
80. Zelber-Sagi, S., Salomone, F., Webb, M., Lotan, R., Yeshua, H., Halpern, Z., et al. Coffee consumption and nonalcoholic fatty liver onset: a prospective study in the general population. Transl Res 165 (2015), 428–436.
81. Anty, R., Marjoux, S., Iannelli, A., Patouraux, S., Schneck, A.S., Bonnafous, S., et al. Regular coffee but not espresso drinking is protective against fibrosis in a cohort mainly composed of morbidly obese European women with NAFLD undergoing bariatric surgery. J Hepatol 57 (2012), 1090–1096.
82. Bambha, K., Wilson, L.A., Unalp, A., Loomba, R., Neuschwander-Tetri, B.A., Brunt, E.M., et al. Coffee consumption in NAFLD patients with lower insulin resistance is associated with lower risk of severe fibrosis. Liver Int 34 (2014), 1250–1258.
83. Catalano, D., Martines, G.F., Tonzuso, A., Pirri, C., Trovato, F.M., Trovato, G.M., Protective role of coffee in non-alcoholic fatty liver disease (NAFLD). Dig Dis Sci 55 (2010), 3200–3206.
84. Birerdinc, A., Stepanova, M., Pawloski, L., Younossi, Z.M., Caffeine is protective in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 35 (2012), 76–82.
85. Setiawan, V.W., Wilkens, L.R., Lu, S.C., Hernandez, B.Y., Le Marchand, L., Henderson, B.E., Association of coffee intake with reduced incidence of liver cancer and death from chronic liver disease in the US multiethnic cohort. Gastroenterology 148 (2015), 118–125 [Quiz e115].
86. Bravi, F., Bosetti, C., Tavani, A., Gallus, S., La Vecchia, C., Coffee reduces risk for hepatocellular carcinoma: an updated meta-analysis. Clin Gastroenterol Hepatol 11 (2013), 1413–1421 e1411.
87. 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, CD004996.
88. Sanyal, A.J., Chalasani, N., Kowdley, K.V., McCullough, A., Diehl, A.M., Bass, N.M., et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 362 (2010), 1675–1685.
89. Wei, J., Lei, G.H., Fu, L., Zeng, C., Yang, T., Peng, S.F., Association between dietary vitamin C intake and non-alcoholic fatty liver disease: a cross-sectional study among middle-aged and older adults. PLoS One, 11, 2016, e0147985.
90. Han, J.M., Jo, A.N., Lee, S.M., Bae, H.S., Jun, D.W., Cho, Y.K., et al. Associations between intakes of individual nutrients or whole food groups and non-alcoholic fatty liver disease among Korean adults. J Gastroenterol Hepatol 29 (2014), 1265–1272.
91. Da Silva, H.E., Arendt, B.M., Noureldin, S.A., Therapondos, G., Guindi, M., Allard, J.P., A cross-sectional study assessing dietary intake and physical activity in Canadian patients with nonalcoholic fatty liver disease vs healthy controls. J Acad Nutr Diet 114 (2014), 1181–1194.
92. Madan, K., Bhardwaj, P., Thareja, S., Gupta, S.D., Saraya, A., Oxidant stress and antioxidant status among patients with nonalcoholic fatty liver disease (NAFLD). J Clin Gastroenterol 40 (2006), 930–935.
93. Chan, R., Wong, V.W., Chu, W.C., Wong, G.L., Li, L.S., Leung, J., et al. Diet-quality scores and prevalence of nonalcoholic fatty liver disease: a population study using proton-magnetic resonance spectroscopy. PLoS One, 10, 2015, e0139310.
94. Guerrerio, A.L., Colvin, R.M., Schwartz, A.K., Molleston, J.P., Murray, K.F., Diehl, A., et al. Choline intake in a large cohort of patients with nonalcoholic fatty liver disease. Am J Clin Nutr 95 (2012), 892–900.
95. Kitson, M.T., Roberts, S.K., D-livering the message: the importance of vitamin D status in chronic liver disease. J Hepatol 57 (2012), 897–909.
96. Abramovitch, S., Dahan-Bachar, L., Sharvit, E., Weisman, Y., Ben Tov, A., Brazowski, E., et al. Vitamin D inhibits proliferation and profibrotic marker expression in hepatic stellate cells and decreases thioacetamide-induced liver fibrosis in rats. Gut 60 (2011), 1728–1737.
97. Eliades, M., Spyrou, E., Agrawal, N., Lazo, M., Brancati, F.L., Potter, J.J., et al. Meta-analysis: vitamin D and non-alcoholic fatty liver disease. Aliment Pharmacol Ther 38 (2013), 246–254.
98. Bril, F., Maximos, M., Portillo-Sanchez, P., Biernacki, D., Lomonaco, R., Subbarayan, S., et al. Relationship of vitamin D with insulin resistance and disease severity in non-alcoholic steatohepatitis. J Hepatol 62 (2015), 405–411.
99. Nelson, J.E., Roth, C.L., Wilson, L.A., Yates, K.P., Aouizerat, B., Morgan-Stevenson, V., et al. Vitamin D deficiency is associated with increased risk of non-alcoholic steatohepatitis in adults with non-alcoholic fatty liver disease: possible role for MAPK and NF-kappaB?. Am J Gastroenterol 111 (2016), 852–863.
100. Spiro, A., Buttriss, J.L., Vitamin D: An overview of vitamin D status and intake in Europe. Nutr Bull 39 (2014), 322–350.
101. Barchetta, I., Del Ben, M., Angelico, F., Di Martino, M., Fraioli, A., La Torre, G., et al. No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. BMC Med, 14, 2016, 92.
102. Kitson, M.T., Pham, A., Gordon, A., Kemp, W., Roberts, S.K., High-dose vitamin D supplementation and liver histology in NASH. Gut 65 (2016), 717–718.
103. Levine, J.A., Sick of sitting. Diabetologia 58 (2015), 1751–1758.
104. Grontved, A., Hu, F.B., Television viewing and risk of type 2 diabetes, cardiovascular disease, and all-cause mortality: a meta-analysis. JAMA 305 (2011), 2448–2455.
105. Laaksonen, D.E., Lakka, H.M., Salonen, J.T., Niskanen, L.K., Rauramaa, R., Lakka, T.A., Low levels of leisure-time physical activity and cardiorespiratory fitness predict development of the metabolic syndrome. Diabetes Care 25 (2002), 1612–1618.
106. Chu, A.H., Moy, F.M., Joint association of sitting time and physical activity with metabolic risk factors among middle-aged Malays in a developing country: a cross-sectional study. PLoS One, 8, 2013, e61723.
107. Dunstan, D.W., Salmon, J., Healy, G.N., Shaw, J.E., Jolley, D., Zimmet, P.Z., et al. Association of television viewing with fasting and 2-h postchallenge plasma glucose levels in adults without diagnosed diabetes. Diabetes Care 30 (2007), 516–522.
108. Wijndaele, K., Healy, G.N., Dunstan, D.W., Barnett, A.G., Salmon, J., Shaw, J.E., et al. Increased cardiometabolic risk is associated with increased TV viewing time. Med Sci Sports Exerc 42 (2010), 1511–1518.
109. Healy, G.N., Dunstan, D.W., Salmon, J., Cerin, E., Shaw, J.E., Zimmet, P.Z., et al. Breaks in sedentary time: beneficial associations with metabolic risk. Diabetes Care 31 (2008), 661–666.
110. Ryu, S., Chang, Y., Jung, H.S., Yun, K.E., Kwon, M.J., Choi, Y., et al. Relationship of sitting time and physical activity with non-alcoholic fatty liver disease. J Hepatol 63 (2015), 1229–1237.
111. Abadi, A., Glover, E.I., Isfort, R.J., Raha, S., Safdar, A., Yasuda, N., et al. Limb immobilization induces a coordinate down-regulation of mitochondrial and other metabolic pathways in men and women. PLoS One, 4, 2009, e6518.
112. Santaliestra-Pasias, A.M., Mouratidou, T., Huybrechts, I., Beghin, L., Cuenca-Garcia, M., Castillo, M.J., et al. Increased sedentary behaviour is associated with unhealthy dietary patterns in European adolescents participating in the HELENA study. Eur J Clin Nutr 68 (2014), 300–308.
113. Morris, J.N., Heady, J.A., Raffle, P.A., Roberts, C.G., Parks, J.W., Coronary heart-disease and physical activity of work. Lancet 265 (1953), 1053–1057.
114. Perseghin, G., Lattuada, G., De Cobelli, F., Ragogna, F., Ntali, G., Esposito, A., et al. Habitual physical activity is associated with intrahepatic fat content in humans. Diabetes Care 30 (2007), 683–688.
115. 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 50 (2009), 68–76.
116. Zelber-Sagi, S., Nitzan-Kaluski, D., Goldsmith, R., Webb, M., Zvibel, I., Goldiner, I., et al. Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study. Hepatology 48 (2008), 1791–1798.
117. Newton, J.L., Jones, D.E., Henderson, E., Kane, L., Wilton, K., Burt, A.D., 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 57 (2008), 807–813.
118. Snowling, N.J., Hopkins, W.G., Effects of different modes of exercise training on glucose control and risk factors for complications in type 2 diabetic patients: a meta-analysis. Diabetes Care 29 (2006), 2518–2527.
119. Thomas, D.E., Elliott, E.J., Naughton, G.A., Exercise for type 2 diabetes mellitus. Cochrane Database Syst Rev, 2006, CD002968.
120. 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 56 (2012), 255–266.
121. Keating, S.E., Hackett, D.A., George, J., Johnson, N.A., Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 57 (2012), 157–166.
122. Hashida, R., Kawaguchi, T., Bekki, M., Omoto, M., Matsuse, H., Nago, T., et al. Aerobic vs. resistance exercise in non-alcoholic fatty liver disease: A systematic review. J Hepatol 66 (2017), 142–152.
123. Keating, S.E., Hackett, D.A., Parker, H.M., O'Connor, H.T., Gerofi, J.A., Sainsbury, A., et al. Effect of aerobic exercise training dose on liver fat and visceral adiposity. J Hepatol 63 (2015), 174–182.
124. Zhang, H.J., He, J., Pan, L.L., Ma, Z.M., Han, C.K., Chen, C.S., et al. Effects of moderate and vigorous exercise on nonalcoholic fatty liver disease: a randomized clinical trial. JAMA Intern Med 176 (2016), 1074–1082.
125. Zhang, H.J., Pan, L.L., Ma, Z.M., Chen, Z., Huang, Z.F., Sun, Q., et al. Long-term effect of exercise on improving fatty liver and cardiovascular risk factors in obese adults: A 1-year follow-up study. Diabetes Obes Metab 19 (2017), 284–289.
126. Pugh, C.J., Sprung, V.S., Jones, H., Richardson, P., Shojaee-Moradie, F., Umpleby, A.M., et al. Exercise-induced improvements in liver fat and endothelial function are not sustained 12 months following cessation of exercise supervision in nonalcoholic fatty liver disease. Int J Obes (Lond) 40 (2016), 1927–1930.
127. Shen, J., Wong, G.L., Chan, H.L., Chan, R.S., Chan, H.Y., Chu, W.C., et al. PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease. J Gastroenterol Hepatol 30 (2015), 139–146.
128. Cuthbertson, D.J., Shojaee-Moradie, F., Sprung, V.S., Jones, H., Pugh, C.J., Richardson, P., et al. Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease. Clin Sci (Lond) 130 (2016), 93–104.
129. Shojaee-Moradie, F., Cuthbertson, D.J., Barrett, M., Jackson, N.C., Herring, R., Thomas, E.L., et al. Exercise training reduces liver fat and increases rates of VLDL clearance but not VLDL production in NAFLD. J Clin Endocrinol Metab 101 (2016), 4219–4228.
130. van der Poorten, D., Milner, K.L., Hui, J., Hodge, A., Trenell, M.I., Kench, J.G., et al. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology 48 (2008), 449–457.
131. Ekstedt, M., Franzen, L.E., Mathiesen, U.L., Thorelius, L., Holmqvist, M., Bodemar, G., et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 44 (2006), 865–873.
132. Hallsworth, K., Thoma, C., Hollingsworth, K.G., Cassidy, S., Anstee, Q.M., Day, C.P., et al. Modified high-intensity interval training reduces liver fat and improves cardiac function in non-alcoholic fatty liver disease: a randomized controlled trial. Clin Sci (Lond) 129 (2015), 1097–1105.
133. Houghton, D., Thoma, C., Hallsworth, K., Cassidy, S., Hardy, T., Burt, A.D., et al. Exercise reduces liver lipids and visceral adiposity in patients with nonalcoholic steatohepatitis in a randomized controlled trial. Clin Gastroenterol Hepatol 15 (2017), 96–102 e3.
134. Fealy, C.E., Haus, J.M., Solomon, T.P., Pagadala, M., Flask, C.A., McCullough, A.J., et al. Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease. J Appl Physiol 2012 (1985), 1–6.
135. Ueno, T., Sugawara, H., Sujaku, K., Hashimoto, O., Tsuji, R., Tamaki, S., et al. Therapeutic effects of restricted diet and exercise in obese patients with fatty liver. J Hepatol 27 (1997), 103–107.
136. Kantartzis, K., Thamer, C., Peter, A., Machann, J., Schick, F., Schraml, C., 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 58 (2009), 1281–1288.
137. Jensen, M.D., Ryan, D.H., Apovian, C.M., Ard, J.D., Comuzzie, A.G., Donato, K.A., et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol 63 (2014), 2985–3023.
138. Peng, L., Wang, J., Li, F., Weight reduction for non-alcoholic fatty liver disease. Cochrane Database Syst Rev, 2011, CD003619.
139. Uusitupa, M., Lifestyle changes and cardiovascular risk reduction in diabetes. Lancet Diabetes Endocrinol 4 (2016), 877–878.
140. Lazo, M., Solga, S.F., Horska, A., Bonekamp, S., Diehl, A.M., Brancati, F.L., et al. Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with type 2 diabetes. Diabetes Care 33 (2010), 2156–2163.
141. Patel, N.S., Doycheva, I., Peterson, M.R., Hooker, J., Kisselva, T., Schnabl, B., et al. Effect of weight loss on magnetic resonance imaging estimation of liver fat and volume in patients with nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 13 (2015), 561–568 e561.
142. Harrison, S.A., Fecht, W., Brunt, E.M., Neuschwander-Tetri, B.A., Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial. Hepatology 49 (2009), 80–86.
143. Eckard, C., Cole, R., Lockwood, J., Torres, D.M., Williams, C.D., Shaw, J.C., et al. Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial. Therap Adv Gastroenterol 6 (2013), 249–259.
144. Ross, R., Hudson, R., Stotz, P.J., Lam, M., Effects of exercise amount and intensity on abdominal obesity and glucose tolerance in obese adults: a randomized trial. Ann Intern Med 162 (2015), 325–334.
145. Vissers, D., Hens, W., Taeymans, J., Baeyens, J.P., Poortmans, J., Van Gaal, L., The effect of exercise on visceral adipose tissue in overweight adults: a systematic review and meta-analysis. PLoS One, 8, 2013, e56415.
146. Look, A.R.G., Wing, R.R., Bolin, P., Brancati, F.L., Bray, G.A., Clark, J.M., et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 369 (2013), 145–154.
147. Byers, T., Sedjo, R.L., Body fatness as a cause of cancer: epidemiologic clues to biologic mechanisms. Endocr Relat Cancer 22 (2015), R125–R134.
148. Promrat, K., Kleiner, D.E., Niemeier, H.M., Jackvony, E., Kearns, M., Wands, J.R., et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 51 (2010), 121–129.
149. Musso, G., Cassader, M., Rosina, F., Gambino, R., Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia 55 (2012), 885–904.
150. Suzuki, A., Lindor, K., St Saver, J., Lymp, J., Mendes, F., Muto, A., et al. Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J Hepatol 43 (2005), 1060–1066.
151. Glass, L.M., Dickson, R.C., Anderson, J.C., Suriawinata, A.A., Putra, J., Berk, B.S., et al. Total body weight loss of >/= 10 % is associated with improved hepatic fibrosis in patients with nonalcoholic steatohepatitis. Dig Dis Sci 60 (2015), 1024–1030.
152. Vilar-Gomez, E., Yasells-Garcia, A., Martinez-Perez, Y., Calzadilla-Bertot, L., Torres-Gonzalez, A., Gra-Oramas, B., et al. Development and validation of a noninvasive prediction model for nonalcoholic steatohepatitis resolution after lifestyle intervention. Hepatology 63 (2016), 1875–1887.
153. Ryan, M.C., Abbasi, F., Lamendola, C., Carter, S., McLaughlin, T.L., Serum alanine aminotransferase levels decrease further with carbohydrate than fat restriction in insulin-resistant adults. Diabetes Care 30 (2007), 1075–1080.
154. Browning, J.D., Baker, J.A., Rogers, T., Davis, J., Satapati, S., Burgess, S.C., Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. Am J Clin Nutr 93 (2011), 1048–1052.
155. Kirk, E., Reeds, D.N., Finck, B.N., Mayurranjan, S.M., Patterson, B.W., Klein, S., Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology 136 (2009), 1552–1560.
156. Haufe, S., Engeli, S., Kast, P., Bohnke, J., Utz, W., Haas, V., et al. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects. Hepatology 53 (2011), 1504–1514.
157. Armstrong, M.J., Gaunt, P., Aithal, G.P., Barton, D., Hull, D., Parker, R., et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 387 (2016), 679–690.
158. Armstrong, M.J., Gaunt, P., Newsome, P.N., Identifying patients with nonalcoholic steatohepatitis that are nonresponders to therapy. Hepatology 64 (2016), 2265–2266.
159. Centis, E., Moscatiello, S., Bugianesi, E., Bellentani, S., Fracanzani, A.L., Calugi, S., et al. Stage of change and motivation to healthier lifestyle in non-alcoholic fatty liver disease. J Hepatol 58 (2013), 771–777.
160. Mlynarsky, L., Schlesinger, D., Lotan, R., Webb, M., Halpern, Z., Santo, E., et al. Non-alcoholic fatty liver disease is not associated with a lower health perception. World J Gastroenterol 22 (2016), 4362–4372.
161. Haufe, S., Haas, V., Utz, W., Birkenfeld, A.L., Jeran, S., Bohnke, J., et al. Long-lasting improvements in liver fat and metabolism despite body weight regain after dietary weight loss. Diabetes Care 36 (2013), 3786–3792.
162. Look AHEAD Research Group, Wing, R.R., Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med 170 (2010), 1566–1575.
163. Look AHEAD Research Group, Eight years weight losses with an intensive lifestyle intervention: the look AHEAD study. Obesity 22 (2014), 5–13.
164. Bellentani, S., Dalle Grave, R., Suppini, A., Marchesini, G., Fatty Liver Italian Network. Behavior therapy for nonalcoholic fatty liver disease: The need for a multidisciplinary approach. Hepatology 47 (2008), 746–754.
165. Kreuter, M.W., Chheda, S.G., Bull, F.C., How does physician advice influence patient behavior? Evidence for a priming effect. Arch Fam Med 9 (2000), 426–433.
166. Loureiro, M.L., Nayga, R.M. Jr., Obesity, weight loss, and physician's advice. Soc Sci Med 62 (2006), 2458–2468.
167. Huang, J., Yu, H., Marin, E., Brock, S., Carden, D., Davis, T., Physicians’ weight loss counseling in two public hospital primary care clinics. Acad Med 79 (2004), 156–161.
168. Merz, C.N., Buse, J.B., Tuncer, D., Twillman, G.B., Physician attitudes and practices and patient awareness of the cardiovascular complications of diabetes. J Am Coll Cardiol 40 (2002), 1877–1881.
169. Zelber-Sagi, S., Bord, S., Dror-Lavi, G., Smith, M.L., Towne, S.D. Jr., Buch, A., et al. Role of illness perception and self-efficacy in lifestyle modification among non-alcoholic fatty liver disease patients. World J Gastroenterol 23 (2017), 1881–1890.
170. Whitlock, E.P., Orleans, C.T., Pender, N., Allan, J., Evaluating primary care behavioral counseling interventions: an evidence-based approach. Am J Prev Med 22 (2002), 267–284.
171. Hallsworth, K., Avery, L., Trenell, M.I., Targeting lifestyle behavior change in adults with NAFLD during a 20-min consultation: summary of the dietary and exercise literature. Curr Gastroenterol Rep, 18, 2016, 11.
172. Hickman, I.J., Jonsson, J.R., Prins, J.B., Ash, S., Purdie, D.M., Clouston, A.D., 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 53 (2004), 413–419.
173. Petersen, K.F., Dufour, S., Befroy, D., Lehrke, M., Hendler, R.E., Shulman, G.I., Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 54 (2005), 603–608.
174. Huang, M.A., Greenson, J.K., Chao, C., Anderson, L., Peterman, D., Jacobson, J., et al. One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study. Am J Gastroenterol 100 (2005), 1072–1081.
175. Zelber-Sagi, S., Kessler, A., Brazowsky, E., Webb, M., Lurie, Y., Santo, M., et al. A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 4 (2006), 639–644.
176. Benjaminov, O., Beglaibter, N., Gindy, L., Spivak, H., Singer, P., Wienberg, M., et al. The effect of a low-carbohydrate diet on the nonalcoholic fatty liver in morbidly obese patients before bariatric surgery. Surg Endosc 21 (2007), 1423–1427.
177. Tendler, D., Lin, S., Yancy, W.S. Jr., Mavropoulos, J., Sylvestre, P., Rockey, D.C., et al. The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study. Dig Dis Sci 52 (2007), 589–593.
178. Yamamoto, M., Iwasa, M., Iwata, K., Kaito, M., Sugimoto, R., Urawa, N., et al. Restriction of dietary calories, fat and iron improves non-alcoholic fatty liver disease. J Gastroenterol Hepatol 22 (2007), 498–503.
179. de Luis, D.A., Aller, R., Izaola, O., Sagrado, M.G., Conde, R., Gonzalez, J.M., Effect of a hypocaloric diet in transaminases in nonalcoholic fatty liver disease and obese patients, relation with insulin resistance. Diabetes Res Clin Pract 79 (2008), 74–78.
180. Oza, N., Eguchi, Y., Mizuta, T., Ishibashi, E., Kitajima, Y., Horie, H., et al. A pilot trial of body weight reduction for nonalcoholic fatty liver disease with a home-based lifestyle modification intervention delivered in collaboration with interdisciplinary medical staff. J Gastroenterol 44 (2009), 1203–1208.
181. St George, A., Bauman, A., Johnston, A., Farrell, G., Chey, T., George, J., Effect of a lifestyle intervention in patients with abnormal liver enzymes and metabolic risk factors. J Gastroenterol Hepatol 24 (2009), 399–407.
182. Viljanen, A.P., Iozzo, P., Borra, R., Kankaanpaa, M., Karmi, A., Lautamaki, R., et al. Effect of weight loss on liver free fatty acid uptake and hepatic insulin resistance. J Clin Endocrinol Metab 94 (2009), 50–55.
183. Vilar Gomez, E., Rodriguez De Miranda, A., Gra Oramas, B., Arus Soler, E., Llanio Navarro, R., Calzadilla Bertot, L., et al. Clinical trial: a nutritional supplement Viusid, in combination with diet and exercise, in patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther 30 (2009), 999–1009.
184. Shah, K., Stufflebam, A., Hilton, T.N., Sinacore, D.R., Klein, S., Villareal, D.T., Diet and exercise interventions reduce intrahepatic fat content and improve insulin sensitivity in obese older adults. Obesity 17 (2009), 2162–2168.
185. Elias, M.C., Parise, E.R., de Carvalho, L., Szejnfeld, D., Netto, J.P., Effect of 6-month nutritional intervention on non-alcoholic fatty liver disease. Nutrition 26 (2010), 1094–1099.
186. Albu, J.B., Heilbronn, L.K., Kelley, D.E., Smith, S.R., Azuma, K., Berk, E.S., et al. Metabolic changes following a 1-year diet and exercise intervention in patients with type 2 diabetes. Diabetes 59 (2010), 627–633.
187. Moscatiello, S., Di Luzio, R., Bugianesi, E., Suppini, A., Hickman, I.J., Di Domizio, S., et al. Cognitive-behavioral treatment of nonalcoholic Fatty liver disease: a propensity score-adjusted observational study. Obesity 19 (2011), 763–770.
188. Sun, W.H., Song, M.Q., Jiang, C.Q., Xin, Y.N., Ma, J.L., Liu, Y.X., et al. Lifestyle intervention in non-alcoholic fatty liver disease in Chengyang District, Qingdao, China. World J Hepatol 4 (2012), 224–230.
189. Scaglioni, F., Marino, M., Ciccia, S., Procaccini, A., Busacchi, M., Loria, P., et al. Short-term multidisciplinary non-pharmacological intervention is effective in reducing liver fat content assessed non-invasively in patients with nonalcoholic fatty liver disease (NAFLD). Clin Res Hepatol Gastroenterol 37 (2013), 353–358.
190. Wong, V.W., Chan, R.S., Wong, G.L., Cheung, B.H., Chu, W.C., Yeung, D.K., et al. Community-based lifestyle modification programme for non-alcoholic fatty liver disease: a randomized controlled trial. J Hepatol 59 (2013), 536–542.
191. Yoshimura, E., Kumahara, H., Tobina, T., Matsuda, T., Ayabe, M., Kiyonaga, A., et al. Lifestyle intervention involving calorie restriction with or without aerobic exercise training improves liver fat in adults with visceral adiposity. J Obes, 2014, 2014, 197216.