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Nichtalkoholische Steatohepatitis

Prädiktor und Folge des Diabetes

Nonalcoholic steatohepatitis

Predictor and consequence of diabetes

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Zusammenfassung

Die nichtalkoholische Fettlebererkrankung (NAFLD) und insbesondere die nichtalkoholische Steatohepatitis (NASH) stellen nicht nur Risikofaktoren für Leberfibrose, Leberzirrhose und das hepatozelluläre Karzinom dar, sondern sind auch stark mit der Insulinresistenz und dem Typ-2-Diabetes assoziiert. Dies liegt wahrscheinlich daran, dass in der Pathogenese dieser Erkrankungen gemeinsame Mechanismen von Bedeutung sind. Darüber hinaus sagen NAFLD und NASH die Erkrankungswahrscheinlichkeit für Typ-2-Diabetes, aber auch für die Atherosklerose voraus, was eine kausale Rolle der Fettleber in der Pathogenese dieser Erkrankungen impliziert. Diese Hypothese wird durch neue Ergebnisse unterstützt, die durch Genotypisierung und Phänotypisierung bei Risikopersonen gewonnen wurden. Die genaue Erforschung der beteiligten Mechanismen wird in der Zukunft wichtige neue Erkenntnisse bringen, die für die Prävention und Therapie dieser Erkrankungen bedeutsam sein werden.

Abstract

Nonalcoholic fatty liver (NAFL) and particularly nonalcoholic steatohepatitis (NASH) are not only risc factors for liver fibrosis, liver zirrhosis and hepatocellular carcinoma, but are also strongly associated with insulin resistance and type 2 diabetes. This is probably due to the fact that the same mechanisms are operative in the pathogenesis of these diseases. In addition fatty liver predicts incident type 2 diabetes, but also atherosclerosis, indicating a causal role of fatty liver in the pathogenesis of these diseases. This hypothesis is supported by novel findings deriving from translational research involving precise genotyping and phenotyping strategies in humans. The precise investigation of mechanisms involved will deliver new knowledge which may be important for the prevention and therapy of these diseases.

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Literatur

  1. Angulo P (2002) Nonalcoholic fatty liver disease. N Engl J Med 346:1221–1231

    Article  PubMed  CAS  Google Scholar 

  2. Campos GM, Bambha K, Vittinghoff E et al (2008) A clinical scoring system for predicting nonalcoholic steatohepatitis in morbidly obese patients. Hepatology 47:1916–1923

    Article  PubMed  Google Scholar 

  3. Di Marzo V (2008) The endocannabinoid system in obesity and type 2 diabetes. Diabetologia 51:1356–1367

    Article  Google Scholar 

  4. Ding EL, Song Y, Manson JE et al (2009) Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med 361:1152–1163

    Article  PubMed  CAS  Google Scholar 

  5. Feldstein AE, Wieckowska A, Lopez AR et al (2009) Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology 50:1072–1078

    Article  PubMed  CAS  Google Scholar 

  6. Ferrario C, Basik M (2010) Physiopathology of colorectal metastasis. Metastasis Colorect Cancer 14:33–64

    Article  CAS  Google Scholar 

  7. Fisher E, Stefan N, Saar K et al (2009) Association of AHSG gene polymorphisms with fetuin-A plasma levels and cardiovascular diseases in the EPIC-Potsdam study. Circ Cardiovasc Genet 2:607–613

    Article  PubMed  CAS  Google Scholar 

  8. Hennige AM, Staiger H, Wicke C et al (2008) Fetuin-A induces cytokine expression and suppresses adiponectin production. PLoS ONE 3:e1765

    Article  PubMed  Google Scholar 

  9. Kantartzis K, Machann J, Schick F et al (2010) The impact of liver fat vs visceral fat in determining categories of prediabetes. Diabetologia 53:882–889

    Article  PubMed  CAS  Google Scholar 

  10. Kantartzis K, Peter A, Machicao F et al (2009) Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene. Diabetes 58:2616–2623

    Article  PubMed  CAS  Google Scholar 

  11. Kantartzis K, Thamer C, Peter A et al (2009) High cardiorespiratory fitness is an independent predictor of the reduction in liver fat during a lifestyle intervention in non-alcoholic fatty liver disease. Gut 58:1281–1288

    Article  PubMed  CAS  Google Scholar 

  12. Patton HM, Lavine JE, Van Natta ML et al (2008) Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology 135:1961.e1–1971.e2

    Article  PubMed  Google Scholar 

  13. Peter A, Kantartzis K, Machann J et al (2010) Relationships of circulating sex hormone-binding globulin with metabolic traits in humans. Diabetes 59:3167–3173

    Article  PubMed  CAS  Google Scholar 

  14. Poynard T, Ratziu V, Charlotte F et al (2006) Diagnostic value of biochemical markers (NashTest) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol 6:34

    Article  PubMed  Google Scholar 

  15. Roden M (2006) Mechanisms of disease: hepatic steatosis in type 2 diabetes – pathogenesis and clinical relevance. Nat Clin Pract Endocrinol Metab 2:335–348

    Article  PubMed  CAS  Google Scholar 

  16. Romeo S, Kozlitina J, Xing C et al (2008) Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 40:1461–1465

    Article  PubMed  CAS  Google Scholar 

  17. Santoro N, Kursawe R, D’Adamo E et al (2010) A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents. Hepatology 52:1281–1290

    Article  PubMed  CAS  Google Scholar 

  18. Solga SF, Alkhuraishe A, Cope K et al (2006) Breath biomarkers and non-alcoholic fatty liver disease: preliminary observations. Biomarkers 11:174–183

    Article  PubMed  CAS  Google Scholar 

  19. Sookoian S, Castaño G, Burgueño AL et al (2009) A diagnostic model to differentiate simple steatosis from nonalcoholic steatohepatitis based on the likelihood ratio form of Bayes theorem. Clin Biochem 42:624–629

    Article  PubMed  Google Scholar 

  20. Stefan N, Fritsche N, Weikert C et al (2008) Plasma fetuin-A levels and the risk of type 2 diabetes. Diabetes 57:2762–2767

    Article  PubMed  CAS  Google Scholar 

  21. Stefan N, Häring HU, Schulze MB (2008) Association of fetuin-A level and diabetes risk. JAMA 300:2247

    Article  PubMed  CAS  Google Scholar 

  22. Stefan N, Hennige AM, Staiger H et al (2006) Alpha2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care 29:853–857

    Article  PubMed  CAS  Google Scholar 

  23. Stefan N, Hennige AM, Staiger H et al (2007) High circulating retinol-binding protein 4 is associated with elevated liver fat but not with total, subcutaneous, visceral, or intramyocellular fat in humans. Diabetes Care 30:1173–1178

    Article  PubMed  CAS  Google Scholar 

  24. Stefan N, Kantartzis K, Häring HU (2008) Causes and metabolic consequences of fatty liver. Endocr Rev 29:939–960

    Article  PubMed  CAS  Google Scholar 

  25. Stefan N, Kantartzis K, Machann J et al (2008) Identification and Characterization of Metabolically Benign Obesity in Humans. Arch Intern Med 168:1609–1616

    Article  PubMed  Google Scholar 

  26. Stefan N, Schick F, Häring HU (2009) Sex hormone-binding globulin and risk of type 2 diabetes. N Engl J Med 61:2675–2676

    Google Scholar 

  27. Sumida Y, Nakashima T, Yoh T et al (2003) Serum thioredoxin levels as a predictor of steatohepatitis in patients with nonalcoholic fatty liver disease. J Hepatol 38:32–38

    Article  PubMed  CAS  Google Scholar 

  28. Szendroedi J, Chmelik M, Schmid AI et al (2009) Abnormal hepatic energy homeostasis in type 2 diabetes. Hepatology 50:1079–1086

    Article  PubMed  CAS  Google Scholar 

  29. Thamer C, Machann J, Stefan N et al (2008) Variations in PPARD Determine the Change in Body Composition during Lifestyle Intervention: A Whole-Body Magnetic Resonance Study. J Clin Endocrinol Metab 93:1497–1500

    Article  PubMed  CAS  Google Scholar 

  30. Tilg H, Moschen AR (2010) Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 52:1836–1846

    Article  PubMed  CAS  Google Scholar 

  31. Tiniakos DG, Vos MB, Brunt EM (2010) Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol 5:145–171

    Article  PubMed  CAS  Google Scholar 

  32. Weikert C, Stefan N, Schulze MB et al (2008) Plasma fetuin-A levels and the risk of myocardial infarction and ischemic stroke. Circulation 118:2555–2562

    Article  PubMed  CAS  Google Scholar 

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  1. Heisenberg-Stipendiat der Deutschen Forschungsgemeinschaft, -, Deutschland

    N. Stefan

  2. Abteilung für Endokrinologie, Diabetologie, Vaskuläre Medizin, Nephrologie und Klinische Chemie, Innere Medizin, Universitätsklinik Tübingen, Mitglied des Deutschen Zentrums für Diabetesforschung (DZD) e.V., Otfried-Müller-Straße 10, 72076, Tübingen, Deutschland

    N. Stefan & H.-U. Häring

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  1. N. Stefan
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  2. H.-U. Häring
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Correspondence to N. Stefan.

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Stefan, N., Häring, HU. Nichtalkoholische Steatohepatitis. Internist 52, 389–394 (2011). https://doi.org/10.1007/s00108-010-2712-4

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  • DOI: https://doi.org/10.1007/s00108-010-2712-4

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