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Nonalcoholic fatty liver disease and metabolic syndrome


Authors: Marek Rác 1;  Ľubomír Skladaný 2
Authors‘ workplace: Hepatologická ambulancia, Interná klinika FN Nitra, VŠ ZaSP sv. Alžbety, Bratislava 1;  Hepatologické, gastroenterologické a transplantačné oddelenie, II. interná klinika SZU a FNsP F. D. Roosevelta, Banská Bystrica 2
Published in: Forum Diab 2018; 7(2): 109-116
Category: Review Article

Overview

Non-alcoholic fatty liver disease (NAFLD) and the metabolic syndrome are conditions with growing prevalence. The relationship between them is complex and bi-directional. The pathophysiological basis in both cases is insulin resistance. Diabesity is reaching the level of a global epidemic. It contributes to the rising prevalence of systemic diseases associated with obesity. Non-alcoholic fatty liver disease has become the most widespread chronic liver disease in developed countries and it is considered a hepatic manifestation of the metabolic syndrome. The spread and burden of the disease has been constantly growing and reaches epidemic levels, affecting 30% of the adult population. In a group of patients with the metabolic syndrome the prevalence of NAFLD is significantly higher compared with the general population. NAFLD is characterized by an increased amount of intrahepatic fat. It occurs in two basic forms. One is non-alcoholic steatosis (NAFL), the other is progressively developing non-alcoholic steatohepatitis (NASH). As opposed to NAFLD, NASH represents a subgroup with increased risk for the progression of fibrosis, cirrhosis or onset of HCC and it is considered to be linked with an increased incidence of cardiovascular events. Obesity and type 2 diabetes mellitus are among the risk factors for the NASH progression. The growing prevalence of NASH in the near future will bring an enormous cohort of our patients to the stage of advanced liver disease. If the effort to reverse the undesirable epidemiological trend fails, NASH will become the most common indication for liver transplantation in the coming decade. The ever increasing trend of development can be observed in the rising incidence of hepatocellular carcinoma in causal relation to NASH [1]. The comprehensive treatment of the metabolic syndrome components and, in future, a treatment aimed at affecting the key pathogenetic mechanisms might change the individual future of patients, as well as the global burden resulting from NASH.

Key words:

diabetes mellitus, insulin resistence, metabolic syndrome, non-alcoholic steatohepatitis, non-alcoholic fatty liver disease, obesity


Sources
  1. Rác M, Koller T, Skladaný Ľ et al. Nealkoholová tuková choroba pečene a hepatocelulárny karcinóm: prehľad a analýza nitrianskeho súboru. Interná Med 2017; 17(4): 167–174.
  2. Chalasani N, Younossi Z, Lavine JE 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 2012;55(6):2005–2023. Dostupné z DOI: <http://dx.doi.org/10.1002/hep.25762>.
  3. Younossi Z, Anstee QM, Marietti M et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2018; 15(1): 11–20. Dostupné z DOI: <http://dx.doi.org/10.1038/nrgastro.2017.109>.
  4. Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 2013; 10(6): 330–344. Dostupné z DOI: <http://dx.doi.org/10.1038/nrgastro.2013.41>.
  5. Angulo P. Nonalcoholic Fatty Liver Disease. N Engl J Med 2002; 346(16): 1221–1231. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMra011775>.
  6. Mazzotti A, Caletti MT, Sasdelli AS et al. Pathophysiology of Nonalcoholic Fatty Liver Disease: Lifestyle-Gut-Gene Interaction. Dig Dis 2016; 34(Suppl 1): S3-S10. Dostupné z DOI: <http://dx.doi.org/10.1159/000447275>.
  7. Bhala N, Angulo P, van der Poorten D et al. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Hepatology 2011;54(4):1208–1216. Dostupné z DOI: <http://dx.doi.org/10.1002/hep.24491>.
  8. Angulo P. Nonalcoholic Fatty Liver Disease and Liver Transplantation. Liver Transpl 2006; 12(4): 523–534. <http://dx.doi.org/10.1002/lt.20738>.
  9. Valenti L, Romeo S, Nobili V et al. Destined to develop NAFLD? The predictors of fatty liver from birth to adulthood. J Hepatol 2016;65(4): 668–670. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jhep.2016.06.010>.
  10. Liu Y-L, Patman GL, Leathart JBS et al. Carriage of the PNPLA3 rs738409 C &gt;G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol 2014; 61(1): 75–81. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jhep.2014.02.030>.
  11. 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(2): 372–384. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jhep.2010.04.008>.
  12. Ekstedt M, Franzén LE, Mathiesen UL et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44(4): 865–873. Dostupné z DOI: <http://dx.doi.org/10.1002/hep.21327>.
  13. Fassio E, Alvarez E, Dominguez N et al. Natural history of nonalcoholic steatohepatitis: A longitudinal study of repeat liver biopsies. Hepatology 2004; 40(4): 820–826. Dostupné z DOI: <http://dx.doi.org/10.1002/hep.20410>.
  14. McPherson S, Hardy T, Henderson E et al. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: Implications for prognosis and clinical management. J Hepatol 2015; 62(5): 1148–1155. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jhep.2014.11.034>.
  15. Porepa L, Ray JG, Sanchez-Romeu P et al. Newly diagnosed diabetes mellitus as a risk factor for serious liver disease. CMAJ 2010; 182(11): E526-E531. Dostupné z DOI: <http://dx.doi.org/10.1503/cmaj.092144>.
  16. Vanni E, Marengo A, Mezzabotta L et al. Systemic Complications of Nonalcoholic Fatty Liver Disease: When the Liver Is Not an Innocent Bystander. Semin Liver Dis 2015; 35(3): 236–249. Dostupné z DOI: <http://dx.doi.org/10.1055/s-0035–1562944>.
  17. Bugianesi E, McCullough AJ, Marchesini G. Insulin resistance: A metabolic pathway to chronic liver disease. Hepatology 2005; 42(5): 987–1000. Dostupné z DOI: <http://dx.doi.org/10.1002/hep.20920>.
  18. Aljada A, Mousa SA. Metformin and neoplasia: Implications and indications. Pharmacol Ther 2012; 133(1): 108–115. Dostupné z DOI: <http://dx.doi.org/10.1016/j.pharmthera.2011.09.004>.
  19. Zhang P, Li H, Tan X et al. Association of metformin use with cancer incidence and mortality: A meta-analysis. Cancer Epidemiol 2013; 37(3): 207–218. Dostupné z DOI: <http://dx.doi.org/10.1016/j.canep.2012.12.009>.
  20. Chen H-P, Shieh J-J, Chang CC et al. Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies. Gut 2013; 62(4): 606–615. Dostupné z DOI: <http://dx.doi.org/10.1136/gutjnl-2011–301708>.
  21. Singh S, Singh PP, Singh AG et al. Statins Are Associated With a Reduced Risk of Hepatocellular Cancer: A Systematic Review and Meta-analysis. Gastroenterology 2013; 144(2): 323–332. Dostupné z DOI: <http://dx.doi.org/10.1053/j.gastro.2012.10.005>.
  22. Calle EE, Rodriguez C, Walker-Thurmond K et al. Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults. N Engl J Med 2003; 348(17): 1625–1638. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa021423>.
  23. Kotronen A, Westerbacka J, Bergholm R et al. Liver Fat in the Metabolic Syndrome. J Clin Endocrinol Metab 2007; 92(9): 3490–3497. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2007–0482>.
  24. Janičko M, Veselíny E, Orenčák R et al. Redefining the alanine aminotransferase upper limit of normal improves the prediction of metabolic syndrome risk. Eur J Gastroenterol Hepatol 2015; 27(4) :405–411.Dostupné z DOI: <http://dx.doi.org/10.1097/MEG.0000000000000297>.
  25. Balkau B, Lange C, Vol S et al. Nine-year incident diabetes is predicted by fatty liver indices: the French D.E.S.I.R. study. BMC Gastroenterol 2010; 10(1): 56. Dostupné z DOI: <http://dx.doi.org/10.1186/1471–230X-10–56>.
  26. Ryysy L, Häkkinen AM, Goto T et al. Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients. Diabetes 2000; 49(5): 749–758. Dostupné z WWW: <http://www.ncbi.nlm.nih.gov/pubmed/10905483>.
  27. de Marco R, Locatelli F, Zoppini G et al. Cause-specific mortality in type 2 diabetes. The Verona Diabetes Study. Diabetes Care 1999; 22(5): 756–761. Dostupné z WWW: http://www.ncbi.nlm.nih.gov/pubmed/10332677.
  28. Dumith SC, Hallal PC, Reis RS et al. Worldwide prevalence of physical inactivity and its association with human development index in 76 countries. Prev Med 2011; 53(1–2): 24–28. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ypmed.2011.02.017>.
  29. Sullivan S, Kirk EP, Mittendorfer B et al. Randomized trial of exercise effect on intrahepatic triglyceride content and lipid kinetics in nonalcoholic fatty liver disease. Hepatology 2012; 55(6): 1738–1745. Dostupné z DOI: <http://dx.doi.org/10.1002/hep.25548>.
  30. Keating SE, Hackett DA, George J et al. Exercise and non-alcoholic fatty liver disease: A systematic review and meta-analysis. J. Hepatol 2012; 57(1): 157–166. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jhep.2012.02.023>.
  31. Oh S, Shida T, Yamagishi K et al. Moderate to vigorous physical activity volume is an important factor for managing nonalcoholic fatty liver disease: A retrospective study. Hepatology 2015; 61(4): 1205–1215. Dostupné z DOI: <http://dx.doi.org/10.1002/hep.27544>.
  32. Rác M, Skladaný Ľ, Szulc A et al. Inactivity and fatty liver disease. Journal of Education Health and Sport 2016; 6(13): 200–210. Dostupné z DOI: <http://dx.doi.org/10.5281/ZENODO.248873>.
  33. Adams LA, Anstee QM. A fatty liver leads to a broken heart? J Hepatol 2016; 65(1): 14–16. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jhep.2016.03.012>.
  34. Vanni E, Marengo A, Mezzabotta L et al. Systemic Complications of Nonalcoholic Fatty Liver Disease: When the Liver Is Not an Innocent Bystander. Semin Liver Dis 2015; 35(3): 236–249. Dostupné z DOI: <http://dx.doi.org/10.1055/s-0035–1562944>.
  35. Sookoian S, Pirola CJ. Non-alcoholic fatty liver disease is strongly associated with carotid atherosclerosis: A systematic review. J Hepatol 2008; 49(4): 600–607. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jhep.2008.06.012>.
  36. Sung KC, Wild SH, Kwag HJ et al. Fatty Liver, Insulin Resistance, and Features of Metabolic Syndrome: Relationships with coronary artery calcium in 10,153 people. Diabetes Care 2012; 35(11): 2359–2364. Dostupné z DOI: <http://dx.doi.org/10.2337/dc12–0515>.
  37. Goland S, Shimoni S, Zornitzki T et al. Cardiac Abnormalities as a New Manifestation of Nonalcoholic Fatty Liver Disease: Echocardiographic and Tissue Doppler Imaging Assessment. J Clin Gastroenterol 2006; 40(10): 949–955. Dostupné z DOI: <http://dx.doi.org/10.1097/01.mcg.0000225668.53673.e6>.
  38. Hallsworth K, Hollingsworth KG, Thoma C et al. Cardiac structure and function are altered in adults with non-alcoholic fatty liver disease. J Hepatol 2013; 58(4): 757–762. <http://dx.doi.org/10.1016/j.jhep.2012.11.015>.
  39. Oni ET, Agatston AS, Blaha MJ et al. A systematic review: Burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; Should we care? Atherosclerosis 2013; 230(2): 258–267. Dostupné z DOI: <http://dx.doi.org/10.1016/j.atherosclerosis.2013.07.052>.
  40. Targher G, Bertolini L, Padovani R et al. Prevalence of Nonalcoholic Fatty Liver Disease and Its Association With Cardiovascular Disease Among Type 2 Diabetic Patients. Diabetes Care 2007; 30(5): 1212–1218. Dostupné z DOI: <http://dx.doi.org/10.2337/dc06–2247>.
  41. Sanyal A, Poklepovic A, Moyneur E et al. Population-based risk factors and resource utilization for HCC: US perspective. Curr Med Res Opin 2010; 26(9): 2183–2191. Dostupné z DOI: <http://dx.doi.org/10.1185/03007995.2010.506375>.
  42. Hashimoto E, Yatsuji S, Tobari M et al. Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. J Gastroenterol 2009; 44(Suppl 19): S89-S95. Dostupné z DOI: <http://dx.doi.org/10.1007/s00535–008–2262-x>.
  43. Rác M, Koller T, Jarčuška P et al. Nonalcoholic Fatty Liver Disease (NAFLD) and Hepatocellular Carcinoma (HCC): Single Centre Experience. Inflamm Intest Dis 2017; 2: 55. Dostupné z DOI: <http://dx.doi.org/10.1159/000478719>.
  44. El–Serag HB, Rudolph KL. Hepatocellular Carcinoma: Epidemiology and Molecular Carcinogenesis. Gastroenterology 2007; 132(7): 2557–2576. Dostupné z DOI: <http://dx.doi.org/10.1053/j.gastro.2007.04.061>.
  45. He G, Yu G-Y, Temkin V et al. Hepatocyte IKKβ/NF-κB Inhibits Tumor Promotion and Progression by Preventing Oxidative Stress-Driven STAT3 Activation. Cancer Cell 2010; 17(3): 286–297. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ccr.2009.12.048>.
  46. Beyoğlu D, Idle JR. The metabolomic window into hepatobiliary disease. J Hepatol 2013; 59(4): 842–858. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jhep.2013.05.030>.
  47. Harrison SA, Fecht W, Brunt EM et al. Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial. Hepatology 2009; 49(1): 80–86. Dostupné z DOI: <http://dx.doi.org/10.1002/hep.22575>.
  48. Hannah WN, Harrison SA. Effect of Weight Loss, Diet, Exercise, and Bariatric Surgery on Nonalcoholic Fatty Liver Disease. Clin Liver Dis 2016; 20(2): 339–350. Dostupné z DOI: <http://dx.doi.org/10.1016/j.cld.2015.10.008>.
  49. Ekstedt M, Hagström H, Nasr P et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 2015; 61(5): 1547–1554. Dostupné z DOI: <http://dx.doi.org/10.1002/hep.27368>.
  50. Bedossa P. [FLIP Pathology Consortium]. Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease. Hepatology 2014; 60(2): 565–575. Dostupné z DOI: <http://dx.doi.org/10.1002/hep.27173>.
  51. Adams LA, Lymp JF, St. Sauver J et al. The Natural History of Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study. Gastroenterology 2005; 129(1): 113–121. Dostupné z DOI: <http://dx.doi.org/10.1053/j.gastro.2005.04.014>.
  52. Neuschwander-Tetri BA. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: The central role of nontriglyceride fatty acid metabolites. Hepatology 2010; 52(2): 774–788. Dostupné z DOI: <http://dx.doi.org/10.1002/hep.23719>.
  53. Peverill W, Powell L, Skoien R. Evolving Concepts in the Pathogenesis of NASH: Beyond Steatosis and Inflammation. Int J Mol Sci 2014; 15(5): 8591–8638. Dostupné z DOI: <http://dx.doi.org/10.3390/ijms15058591>.
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