Nichtalkoholische Fettlebererkrankung

Zusammenfassung

Im Zuge der Übergewichtsepidemie und der verbreiteten muskulären Inaktivität hat sich die nichtalkoholische Fettlebererkrankung (Non Alcoholic Fatty Liver Disease, NAFLD) als neue Volkskrankheit etabliert. Kennzeichnend hierfür ist eine übermäßige Lipidakkumulation des Lebergewebes mit oder ohne entzündliche Veränderungen. Die NAFLD ist dabei keine isolierte Lebererkrankung, sondern ein unabhängiger Risikofaktor für Typ-2-Diabetes, kardiovaskuläre Erkrankungen sowie chronische Nierenerkrankungen. Die Diagnose der NAFLD wird mittels Leberbiopsie oder durch sonografische bzw. mithilfe laborchemischer und anthropometrischer Verfahren gestellt. Die Basistherapie der NAFLD fußt auf der Lebensstilintervention mit dem Ziel der Leberentfettung und der damit verbundenen Stoffwechselnormalisierung. Eine spezifische Arzneimitteltherapie existiert bislang für diese Indikation nicht.

Nichtalkoholische Fettleber - Insulinresistenz - Typ-2-Diabetes - Ernährungstherapie - Formula-Diät

• Literatur

• 1 Levene AP, Goldin RD. The epidemiology, pathogenesis and histopathology of fatty liver disease. Histopathology 2012; 61: 141-152
• 2 Stefan N, Häring HU. The metabolically benign and malignant fatty liver. Diabetes 2011; 60: 2011-2017
• 3 Ströhle A, Stein J. Nichtalkoholische Fettlebererkrankung. Pathophysiologisch orientierte Diagnostik und Therapie Med Monatsschr Pharm 2015; 38 (5): 166-178
• 4 Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol 2015; 62 (1 Suppl.): S47-64
• 5 Taylor R. Type 2 Diabetes: Etiology and rever-sibility. Diabetes Care 2013; 36: 1047-1055
• 6 Taylor R. Banting Memorial lecture 2012: reversing the twin cycles of type 2 diabetes. Diabet Med 2013; 30: 267-275
• 7 Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 2013; 10: 330-344
• 8 Jäger S, Jacobs S, Kroger J et al. Association between the fatty liver index and risk of type 2 diabetes in the EPIC-Potsdam Study. PLoS One 2015; 10 e0124749
• 9 Byrne CD, Targher G. Ectopic fat, insulin resistance, and nonalcoholic fatty liver disease: implications for cardiovascular disease. Arterioscler Thromb Vasc Biol 2014; 34: 1155-1161
• 10 Than NN, Newsome PN. A concise review of non-alcoholic fatty liver disease. Atherosclerosis 2015; 239: 192-202
• 11 Targher G, Chonchol MB, Byrne CD. CKD and nonalcoholic fatty liver disease. Am J Kidney Dis 2014; 64: 638-652
• 12 Musso G, Gambino R, Tabibian JH et al. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Med 2014; 11 e1001680
• 13 Yki-Jarvinen H. Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol 2014; 2: 901-910
• 14 Chalasani N, Younossi Z, Lavine JE et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 2012; 142: 1592-1609
• 15 Vos B, Moreno C, Nagy N et al. Lean non-alcoholic fatty liver disease (Lean-NAFLD): a major cause of cryptogenic liver disease. Acta Gastroenterol Belg 2011; 74: 389-394
• 16 Younossi ZM, Stepanova M, Negro F et al. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine (Baltimore) 2012; 91: 319-327
• 17 Fukuda T, Hamaguchi M, Kojima T et al. The impact of non-alcoholic fatty liver disease on incident type 2 diabetes mellitus in non-overweight individuals. Liver Int 2016; 36: 275-283
• 18 Eissing L, Scherer T, Todter K et al. De novo lipogenesis in human fat and liver is linked to ChREBP-beta and metabolic health. Nat Commun 2013; 4: 1528
• 19 Zong G, Zhu J, Sun L et al. Associations of erythrocyte fatty acids in the de novo lipogenesis pathway with risk of metabolic syndrome in a cohort study of middle-aged and older Chinese. Am J Clin Nutr 2013; 98: 319-326
• 20 Jacobs S, Jager S, Jansen E et al. Associations of erythrocyte fatty acids in the de novo lipogenesis pathway with proxies of liver fat accumulation in the EPIC-Potsdam Study. PLoS One 2015; 10 e0127368
• 21 Lambert JE, Ramos-Roman MA, Browning JD, Parks EJ. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology 2014; 146: 726-735
• 22 Donnelly KL, Smith CI, Schwarzenberg SJ et al. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005; 115: 1343-1351
• 23 Schwarz JM, Linfoot P, Dare D, Aghajanian K. Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets. Am J Clin Nutr 2003; 77: 43-50
• 24 Martens EA, Gatta-Cherifi B, Gonnissen HK, Westerterp-Plantenga MS. The potential of a high protein-low carbohydrate diet to preserve intrahepatic triglyceride content in healthy humans. PLoS One 2014; 9 e109617
• 25 Chiu S, Sievenpiper JL, de Souza RJ et al. Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials. Eur J Clin Nutr 2014; 68: 416-423
• 26 Chung M, Ma J, Patel K et al. Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis. Am J Clin Nutr 2014; 100: 833-849
• 27 Green CJ, Hodson L. The influence of dietary fat on liver fat accumulation. Nutrients 2014; 6: 5018-5033
• 28 Monteiro J, Leslie M, Moghadasian MH et al. The role of n – 6 and n – 3 polyunsaturated fatty acids in the manifestation of the metabolic syndrome in cardiovascular disease and non-alcoholic fatty liver disease. Food Funct 2014; 5: 426-435
• 29 Oya J, Nakagami T, Sasaki S et al. Intake of n-3 polyunsaturated fatty acids and non-alcoholic fatty liver disease: a cross-sectional study in Japanese men and women. Eur J Clin Nutr 2010; 64: 1179-1185
• 30 Petit JM, Guiu B, Duvillard L et al. Increased erythrocytes n-3 and n-6 polyunsaturated fatty acids is significantly associated with a lower prevalence of steatosis in patients with type 2 diabetes. Clin Nutr 2012; 31: 520-525
• 31 Lou DJ, Zhu QQ, Si XW et al. Serum phospho-lipid omega-3 polyunsaturated fatty acids and insulin resistance in type 2 diabetes mellitus and non-alcoholic fatty liver disease. J Diabetes Complications 2014; 28: 711-714
• 32 Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology 2014; 146: 1513-1524
• 33 Kwok RM, Torres DM, Harrison SA. Vitamin D and NAFLD: Is it more than just an association?. Hepatology 2013; 58: 1166-1174
• 34 Cao Y. Angiogenesis as a therapeutic target for obesity and metabolic diseases. Chem Immunol Allergy 2014; 99: 170-179
• 35 Goossens GH, Blaak EE. Adipose tissue dysfunction and impaired metabolic health in human obesity: a matter of oxygen?. Front Endocrinol (Lausanne) 2015; 6: 55
• 36 Moreno-Indias I, Tinahones FJ. Impaired adipose tissue expandability and lipogenic capacities as ones of the main causes of metabolic disorders. J Diabetes Res 2015; 2015 970375
• 37 Grant RW, Stephens JM. Fat in flames: influence of cytokines and pattern recognition receptors on adipocyte lipolysis. Am J Physiol Endocrinol Metab 2015; 309: E205-213
• 38 Perry RJ, Samuel VT, Petersen KF, Shulman GI. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature 2014; 510: 84-91
• 39 Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med 2014; 371: 1131-1141
• 40 Cao Y. Angiogenesis and vascular functions in modulation of obesity, adipose metabolism, and insulin sensitivity. Cell Metab 2013; 18: 478-489
• 41 Petersen KF, Dufour S, Savage DB et al. The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome. Proc Natl Acad Sci U S A 2007; 104: 12587-12594
• 42 Samuel VT, Shulman GI. Mechanisms for insulin resistance: common threads and missing links. Cell 2012; 148: 852-871
• 43 Roeb E, Steffen HM, Bantel H, Baumann U. S2k Leitlinie: Nicht-alkoholische Fettlebererkrankungen. AWMF-Leitlinie. Register Nr. 021-025. Stand 28.02.2015
• 44 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 2012; 55: 885-904
• 45 Keating SE, George J, Johnson NA. The benefits of exercise for patients with non-alcoholic fatty liver disease. Expert Rev Gastroenterol Hepatol 2015; 9: 1247-1250
• 46 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
• 47 Taylor R, Holman RR. Normal weight individuals who develop type 2 diabetes: the personal fat threshold. Clin Sci (Lond) 2015; 128: 405-410
• 48 Hession M, Rolland C, Kulkarni U et al. Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities Obes Rev 2009; 10: 36-50
• 49 Hu T, Mills KT, Yao L et al. Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol 2012; 176 (Suppl. 7): S44-54
• 50 Ströhle A, Worm N. Metabolisches Syndrom: Pathophysiologische Grundlagen und rationale Empfehlungen zur Ernährungstherapie. Deutsche Apotheker Ztg 2012; 152 (1): 50-67
• 51 Larson-Meyer DE, Newcomer BR, Heilbronn LK et al. Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function. Obesity (Silver Spring) 2008; 16: 1355-1362
• 52 Viljanen AP, Iozzo P, Borra R et al. Effect of weight loss on liver free fatty acid uptake and hepatic insulin resistance. J Clin Endocrinol Metab 2009; 94: 50-55
• 53 Lin WY, Wu CH, Chu NF, Chang CJ. Efficacy and safety of very-low-calorie diet in Taiwanese: a multicenter randomized, controlled trial. Nutrition 2009; 25: 1129-1136
• 54 Lazo M, Solga SF, 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
• 55 Elias MC, Parise ER, de Carvalho L et al. Effect of 6-month nutritional intervention on non-alcoholic fatty liver disease. Nutrition 2010; 26: 1094-1099
• 56 Yu H, Jia W, Guo Z. Reducing liver fat by low carbohydrate caloric restriction targets hepatic glucose production in non-diabetic obese adults with non-alcoholic fatty liver disease. J Clin Med 2014; 3: 1050-1063
• 57 Browning JD, Davis J, Saboorian MH, Burgess SC. A low-carbohydrate diet rapidly and dramatically reduces intrahepatic triglyceride content. Hepatology 2006; 44: 487-488
• 58 Browning JD, Baker JA, Rogers T et al. Short-term weight loss and hepatic tri-glyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction. Am J Clin Nutr 2011; 93: 1048-1052
• 59 Bian H, Hakkarainen A, Lundbom N, Yki-Jarvinen H. Effects of dietary interventions on liver volume in humans. Obesity (Silver Spring) 2014; 22: 989-995
• 60 Kirk E, Reeds DN, Finck BN et al. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology 2009; 136: 1552-1560
• 61 Bozzetto L, Prinster A, Annuzzi G et al. Liver fat is reduced by an isoenergetic MUFA diet in a controlled randomized study in type 2 diabetic patients. Diabetes Care 2012; 35: 1429-1435
• 62 Ryan MC, Itsiopoulos C, Thodis T et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol 2013; 59: 138-143
• 63 Johansson K, Neovius M, Hemmingsson E. Effects of anti-obesity drugs, diet, and exercise on weight-loss maintenance after a very-low-calorie diet or low-calorie diet: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr 2014; 99: 14-23
• 64 Purcell K, Sumithran P, Prendergast LA et al. The effect of rate of weight loss on long-term weight management: a randomised controlled trial. Lancet Diabetes Endocrinol 2014; 2: 954-962
• 65 Heymsfield SB, van Mierlo CA, van der Knaap HC et al. Weight management using a meal replacement strategy: meta and pooling analysis from six studies. Int J Obes Relat Metab Disord 2003; 27: 537-549
• 66 Franz MJ, Van Wormer JJ, Crain AL et al. Weight-loss outcomes: a systematic review and meta-analysis of weight-loss clinical trials with a minimum 1-year follow-up. J Am Diet Assoc 2007; 107: 1755-1767
• 67 Asher RC, Burrows TL, Collins CE. Very low-energy diets for weight loss in adults: A review. Nutrition 2013; 70: 101-112
• 68 Tsai AG, Wadden TA. The evolution of very-low-calorie diets: an update and meta-analysis. Obesity (Silver Spring) 2006; 14: 1283-1293
• 69 Hamdy O, Zwiefelhofer D. Weight management using a meal replacement strategy in type 2 diabetes. Curr Diab Rep 2010; 10: 159-164
• 70 Larson-Meyer DE, Heilbronn LK, Redman LM et al. Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects. Diabetes Care 2006; 29: 1337-1344
• 71 Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA. Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial. Hepatology 2009; 49: 80-86
• 72 Lim EL, Hollingsworth KG, Aribisala BS et al. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011; 54: 2506-2514
• 73 Hemmingsen B, Lund SS, Gluud C et al. Intensive glycaemic control for patients with type 2 diabetes: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. BMJ 2011; 3438 d689
• 74 Anderson JW, Konz EC, Frederich RC, Wood CL. Long-term weight-loss maintenance: a meta-analysis of US studies. Am J Clin Nutr 2001; 74: 579-584
• 75 Hemmingsson E, Johansson K, Eriksson J et al. Weight loss and dropout during a commercial weight-loss program including a very-low-calorie diet, a low-calorie diet, or restricted normal food: observational cohort study. Am J Clin Nutr 2012; 96: 953-961
• 76 Teutsch M. Effekte einer auf Leberentfettung abgestimmten ergänzenden bilanzierten Diät auf Stoffwechsel und Anthropometrie. Adipositas 2014; 8: 177-234
• 77 Bedogni G, Bellentani S, Miglioli L et al. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol 2006; 6: 33
• 78 Arslanow A, Teutsch M, Walle H et al. Two week protein-enriched low-calorie diet (HEPAFAST) shows rapid improvement of fatty liver as assessed by controlled attenuation parameter. Diabetologie und Stoffwechsel 2015; 10 (Suppl. 1) P286
• 79 Ströhle A, Wolters M, Hahn A. Gesundheitliche Effekte von Ballaststoffen. Ein Update Teil 1: Von der Struktur zur Funktion Deutsche Apotheker Ztg 2012; 152 (31): 40-48
• 80 Ströhle A, Wolters M, Hahn A. Gesundheitliche Effekte von Ballaststoffen. Ein Update Teil 2: Systemische Effekte und Präventionspotenzial Deutsche Apotheker Ztg 2012; 152 (32): 54-65
• 81 Abenavoli L. Non-alcoholic fatty liver disease and beneficial effects of dietary supplements. World J Hepatol 2015; 7: 1723-1724