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Adipositas - Ursachen, Folgeerkrankungen, Therapie 2017; 11(01): 4-8
DOI: 10.1055/s-0037-1618950
DOI: 10.1055/s-0037-1618950
Übersichtsarbeit
Die nicht-alkoholische Fettlebererkrankung: Eine Systemerkrankung
Clinical presentation and long-term consequences of non-alcoholic fatty liver disease (NAFLD)Further Information
Publication History
Publication Date:
29 December 2017 (online)
Zusammenfassung
Die nicht-alkoholische Fettlebererkrankung (NAFLD) ist die führende Lebererkrankung in der westlichen Welt und zeitgleich zentraler Bestandteil des metabolischen Syndroms. Ihr Spektrum reicht von der simplen Steatose über die nicht-alkoholische Fettleberhepatitis (NASH) und führt nicht selten in eine Fibrose mit anschließender Leberzirrhose, welche im hepatozellulären Karzinom enden kann. Dieser Progress verdeutlicht, dass die NAFLD nicht wie lange Zeit angenommen als „benigne” oder triviale Begleiterscheinung verkannt werden darf. Im Gegenteil, die NAFLD zeigt sich als eigenständiger Risikofaktor hinsichtlich der Entwicklung eines Diabetes mellitus Typ 2, Herzkreislauferkrankungen, chronischer Nephropathie und extrahepatischer Karzinome. Aufgrund dieser Zusammenhänge bedürfen NAFLD-Patienten umfassender Screeninguntersuchungen, um etwaige Entwicklungen frühzeitig zu detektieren.
Summary
Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading liver disease within the Western population and it is strongly associated with obesity and the metabolic syndrome. The pathological spectrum of NAFLD comprises simple hepatic steatosis, nonalcoholic steatohepatitis (NASH) as well as liver fibrosis with consecutive development of liver cirrhosis leading to hepatocellular carcinoma (HCC; tumors with poor clinical outcome and limited therapeutic options that also can develop in non-cirrhotic livers). Thus, NAFLD can not longer be considered a benign accompanying symptom, but rather an independent risk factor for type 2 diabetes mellitus, cardiovascular disease, chronic nephropathy, and extrahepatic malignancies. Given the increasingly acknowledged pathological relevance in combination with prevalence rates that reach epidemic proportions worldwide, a more thorough diagnostic evaluation of patients suffering from NAFLD is highly desirable to prevent numerous subsequent diseases.
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Literatur
- 1 Seyda GSeydel, Kucukoglu O, Altinbasv A. et al. Economic growth leads to increase of obesity and associated hepatocellular carcinoma in developing countries. Ann Hepatol 2016; 15 (05) 662-672.
- 2 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 (07) 1592-1609.
- 3 Ertle J, Dechêne A, Sowa J-P. et al. Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. Int J Cancer J Int Cancer 2011; 128 (10) 2436-2443.
- 4 Bechmann LP, Hannivoort RA, Gerken G, Hotamisligil GS, Trauner M, Canbay A. The interaction of hepatic lipid and glucose metabolism in liver diseases. J Hepatol 2012; 56 (04) 952-964.
- 5 Younossi ZM, Koenig AB, Abdelatif D. et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatol 2016; 64 (01) 73-84.
- 6 Kim CH, Younossi ZM. Nonalcoholic fatty liver disease: a manifestation of the metabolic syndrome. Cleve Clin J Med 2008; 75 (10) 721-728.
- 7 Garaulet M, Hernandez-Morante JJ, Lujan J, Tebar FJ, Zamora S. Relationship between fat cell size and number and fatty acid composition in adipose tissue from different fat depots in overweight/ obese humans. Int J Obes 2006; 30 (06) 899-905.
- 8 Jernås M, Palming J, Sjöholm K. et al. Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression. FASEB J Off Publ Fed Am Soc Exp Biol 2006; 20 (09) 1540-1542.
- 9 Skurk T, Alberti-Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 2007; 92 (03) 1023-1033.
- 10 Canbay A, Chen S-Y, Gieseler RK. et al. Overweight patients are more susceptible for acute liver failure. Hepatogastroenterol 2005; 52 (65) 1516-1520.
- 11 Kälsch J, Keskin H, Schütte A. et al. Patients with ultrasound diagnosis of hepatic steatosis are at high metabolic risk. Z Gastroenterol 2016; 54 (12) 1312-1319.
- 12 Wree A, Schlattjan M, Bechmann LP. et al. Adipocyte cell size, free fatty acids and apolipoproteins are associated with non-alcoholic liver injury progression in severely obese patients. Metabolism 2014; 63 (12) 1542-1552.
- 13 Cantley J. The control of insulin secretion by adipokines: current evidence for adipocyte-beta cell endocrine signalling in metabolic homeostasis. Mamm Genome 2014; 25 9-10 442-454.
- 14 Park H-K, Ahima RS. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism 2015; 64 (01) 24-34.
- 15 Nakata M, Okada T, Ozawa K, Yada T. Resistin induces insulin resistance in pancreatic islets to impair glucose-induced insulin release. Biochem Biophys Res Commun 2007; 353 (04) 1046-1051.
- 16 Danielsson T, Fredriksson L, Jansson L. et al. Resistin increases islet blood flow and decreases subcutaneous adipose tissue blood flow in anaesthetized rats. Acta Physiol 2009; 195 (02) 283-288.
- 17 Dutchak PA, Katafuchi T, Bookout AL. et al. Fibroblast growth factor-21 regulates PPARγ activity and the antidiabetic actions of thiazolidinediones. Cell 2012; 148 (03) 556-567.
- 18 Holland WL, Adams AC, Brozinick JT. et al. An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice. Cell Metab 2013; 17 (05) 790-797.
- 19 Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006; 444 7121 860-867.
- 20 Asrih M, Jornayvaz FR. Inflammation as a potential link between nonalcoholic fatty liver disease and insulin resistance. J Endocrinol 2013; 218 (03) R25-36.
- 21 Sato T, Ida T, Nakamura Y. et al. Physiological roles of ghrelin on obesity. Obes Res Clin Pract 2014; 08 (05) e405-413.
- 22 Unger RH. Lipid overload and overflow: metabolic trauma and the metabolic syndrome. Trends Endocrinol Metab TEM 2003; 14 (09) 398-403.
- 23 Brookheart RT, Michel CI, Schaffer JE. As a matter of fat. Cell Metab 2009; 10 (01) 9-12.
- 24 Trauner M, Arrese M, Wagner M. Fatty liver and lipotoxicity. Biochim Biophys Acta 2010; 1801 (03) 299-310.
- 25 Kubes P, Mehal WZ. Sterile inflammation in the liver. Gastroenterology 2012; 143 (05) 1158-1172.
- 26 Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatol 2010; 52 (05) 1836-1846.
- 27 Canbay A, Friedman S, Gores GJ. Apoptosis: the nexus of liver injury and fibrosis. Hepatol 2004; 39 (02) 273-278.
- 28 Canbay A, Taimr P, Torok N. et al. Apoptotic body engulfment by a human stellate cell line is profibrogenic. Lab Investig J Tech Methods Pathol 2003; 83 (05) 655-663.
- 29 Begriche K, Igoudjil A, Pessayre D, Fromenty B. Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it. Mitochondrion 2006; 06 (01) 1-28.
- 30 Angulo P, Lindor KD. Non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2002; 17 (Suppl): S186-90.
- 31 Shao W, Espenshade PJ. Expanding roles for SREBP in metabolism. Cell Metab 2012; 16 (04) 414-419.
- 32 Bugianesi E, McCullough AJ, Marchesini G. Insulin resistance: a metabolic pathway to chronic liver disease. Hepatol 2005; 42 (05) 987-1000.
- 33 Montane J, Cadavez L, Novials A. Stress and the inflammatory process: a major cause of pancreatic cell death in type 2 diabetes. Diabetes Metab Syndr Obes Targets Ther 2014; 07: 25-34.
- 34 Quan W, Jo E-K, Lee M-S. Role of pancreatic β-cell death and inflammation in diabetes. Diabetes Obes Metab 2013; 15 (Suppl. 03) 141-151.
- 35 Vanni E, Bugianesi E, Kotronen A. et al. From the metabolic syndrome to NAFLD or vice versa?. Dig Liver Dis Off J Ital Soc Gastroenterol Ital Assoc Study Liver 2010; 42 (05) 320-330.
- 36 Dietrich P, Hellerbrand C. Non-alcoholic fatty liver disease, obesity and the metabolic syndrome. Best Pract Res Clin Gastroenterol 2014; 28 (04) 637-653.
- 37 WHO. Cardiovascular diseases (CVDs) [zitiert 4. Dezember 2016]. Verfügbar unter: http://www.who.int/mediacentre/factsheets/fs317/en/
- 38 Ahmed MH, Barakat S, Almobarak AO. Nonalcoholic fatty liver disease and cardiovascular disease: has the time come for cardiologists to be hepatologists?. J Obes 2012; 2012: 483135.
- 39 Mellinger JL, Pencina KM, Massaro JM. et al. Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study. J Hepatol 2015; 63 (02) 470-476.
- 40 Kim NH, Park J, Kim SH. et al. Non-alcoholic fatty liver disease, metabolic syndrome and subclinical cardiovascular changes in the general population. Heart 2014; 100 (12) 938-943.
- 41 Fotbolcu H, Yakar T, Duman D. et al. Aortic elastic properties in nonalcoholic fatty liver disease. Blood Press Monit 2010; 15 (03) 139-145.
- 42 Sunbul M, Agirbasli M, Durmus E. et al. Arterial stiffness in patients with non-alcoholic fatty liver disease is related to fibrosis stage and epicardial adipose tissue thickness. Atherosclerosis 2014; 237 (02) 490-493.
- 43 Vlachopoulos C, Manesis E, Baou K. et al. Increased arterial stiffness and impaired endothelial function in nonalcoholic Fatty liver disease: a pilot study. Am J Hypertens 2010; 23 (11) 1183-1189.
- 44 Hoffman EP, Barr ML, Giovanni MA. et al. (Eds) GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993 [zitiert 29. September 2015]. Verfügbar unter. http://www.ncbi.nlm.nih.gov/books/NBK305870
- 45 Baars T, Neumann U, Jinawy M. et al. In Acute Myocardial Infarction Liver Parameters Are Associated With Stenosis Diameter. Medicine 2016; 95 (06) e2807.
- 46 Morton RL, Schlackow I, Mihaylova B. et al. The impact of social disadvantage in moderate-to-severe chronic kidney disease: an equity-focused systematic review. Nephrol Dial Transplant 2016; 31 (01) 46-56.
- 47 Targher G, Bertolini L, Rodella S. et al. Relationship between kidney function and liver histology in subjects with nonalcoholic steatohepatitis. Clin J Am Soc Nephrol 2010; 05 (12) 2166-2171.
- 48 Targher G, Bertolini L, Rodella S. et al. Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients. Diabetologia 2008; 51 (03) 444-450.
- 49 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 (07) e1001680.
- 50 Pacifico L, Bonci E, Andreoli GM. et al. The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity. Int J Mol Sci. 2016 17. 08.
- 51 Armstrong MJ, Adams LA, Canbay A, Syn W-K. Extrahepatic complications of nonalcoholic fatty liver disease. Hepatol 2014; 59 (03) 1174-1197.
- 52 Sanna C, Rosso C, Marietti M, Bugianesi E. Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers. Int J Mol Sci. 2016 17. 05.
- 53 Mikolasevic I, Orlic L, Stimac D. et al. Non-alcoholic fatty liver disease and colorectal cancer. Postgrad Med J. 2016
- 54 Kälsch J, Keskin H, Schütte A. et al. Patients with ultrasound diag-nosis of hepatic steatosis are at high metabolic risk. Z Gastroenterol 2016; 54 (12) 1312-1319.