Liver and Metabolic Syndrome
Epidemiology of Non-Alcoholic Fatty Liver DiseaseBellentani S.a · Scaglioni F.a · Marino M.a · Bedogni G.a, b
aCentro Studi Fegato, Azienda USL di Modena, Carpi, and bCentro Studi Fegato, Trieste, Italy
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. The prevalence of NAFLD in the general population of Western countries is 20–30%. About 2–3% of the general population is estimated to have non-alcoholic steatohepatitis (NASH), which may progress to liver cirrhosis and hepatocarcinoma. As a rule, the prevalence of NAFLD is higher in males and increases with increasing age, and it is influenced by the diagnostic method and the characteristics of the population, especially lifestyle habits. Population-based studies provide better estimates of the prevalence of NAFLD as compared to autoptic and clinical studies, but few such studies have been performed to date. The diagnosis of NAFLD in population studies is usually obtained by ultrasonography, which is known to underestimate the prevalence of fatty liver. The Dallas Heart Study and the Dionysos Study reported that 30% of the adults in the USA and 25% in Italy have NAFLD. In these studies, 79% and 55% of patients with NAFLD had normal aminotransferase levels, showing that liver enzymes are not surrogate markers of NAFLD in the general population. Noninvasive markers such as the fatty liver index obtained from the Dionysos Study may be useful to screen for NAFLD in the general population. The most important risk factors for NAFLD are male gender, age, obesity, insulin resistance and the cardiometabolic alterations that define the metabolic syndrome. The prevalence of NAFLD is 80–90% in obese adults, 30–50% in patients with diabetes and up to 90% in patients with hyperlipidemia. The prevalence of NAFLD among children is 3–10%, rising up to 40–70% among obese children. Moreover, pediatric NAFLD increased from about 3% a decade ago to 5% today, with a male-to-female ratio of 2:1. The incidence and natural history of NAFLD are still not well defined, but it is recognized that the majority of individuals with NAFLD do not develop NASH. The incidence of NAFLD is probably increasing in Western countries, strictly linked to lifestyle habits.
© 2010 S. Karger AG, Basel
- Angulo P, Lindor KD: Non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2002;17(Suppl):S186–S190.
- Neuschwander-Tetri BA, Caldwell SH: Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003;37:1202–1219.
- Angulo P: Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221–1231.
- Lonardo A, Loria P: NAFLD and cardiovasular risk: direct evidence for the tale of two ages. Am J Gastroenterol 2009;104:1851–1852.
- Falck-Ytter Y, Younossi ZM, Marchesini G, McCullough AJ: Clinical features and natural history of nonalcoholic steatosis syndromes. Semin Liver Dis 2001;21:17–26.
- Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, Forlani G, Melchionda N: Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 1999;107:450–455.
- Lonardo A, Lombardini S, Ricchi M, Scaglioni F, Loria P: Review article: hepatic steatosis and insulin resistance. Aliment Pharmacol Ther 2005;22(suppl 2):64–70.
- Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, Vanni E, Villanova N, Melchionda N, Rizzetto M: Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003;37:917–923.
- Bellentani S, Marino M: Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD). Ann Hepatol 2009;8(suppl 1):S4–S8.
- Graham A: Curcumin adds spice to the debate: lipid metabolism in liver disease. Br J Pharmacol 2009;157:1352–1353.
- Alkhouri N, Dixon LJ, Feldstein AE: Lipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equal. Expert Rev Gastroenterol Hepatol 2009;3:445–451.
- Fujita K, Nozaki Y, Wada K, Yoneda M, Fujimoto Y, Fujitake M, Endo H, Takahashi H, Inamori M, Kobayashi N, Kirikoshi H, Kubota K, Saito S, Nakajima A: Dysfunctional very-low-density lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis. Hepatology 2009;50:772–780.
- Bedogni G, Bellentani S: Fatty liver: How frequent is it and why? Ann Hepatology 2004;3:63–65.
- Loria P, Lonardo A, Carulli N: Should nonalcoholic fatty liver disease be renamed? Dig Dis 2005;23:72–82.
Dorland NW: Dorland’s Illustrated Medical Dictionary, ed. 28. Philadelphia, WB Saunders Company, 1994.
- Guzman G, Brunt EM, Petrovic LM, Chejfec G, Layden TJ, Cotler SJ: Does nonalcoholic fatty liver disease predispose patients to hepatocellular carcinoma in the absence of cirrhosis? Arch Pathol Lab Med 2008;132:1761–1766.
- Nakanishi Y, Tsuneyama K, Nomoto K, Fujimoto M, Salunga TL, Nakajima T, Miwa S, Murai Y, Hayashi S, Kato I, Hiraga K, Hsu DK, Liu FT, Takano Y: Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin-3 knockout mice. Hepatol Res 2008;38:1241–1251.
- Clark JM, Diehl AM: Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis. JAMA 2003;289:3000–3004.
- Björnsson E, Angulo P: Non-alcoholic fatty liver disease. Scand J Gastroenterol 2007;42:1023–1030.
- Hilden M, Christoffersen P, Juhl E, Dalgaard JB: Liver histology in a ‘normal’ population: examinations of 503 consecutive fatal traffic casualties. Scand J Gastroenterol 1977;12: 593–597.
- Ground KE: Liver pathology in aircrew. Aviat Space Environ Med 1982;53:14–18.
- Wanless IR, Lentz JS: Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology 1990;12:1106–1110.
- McCullough AJ: The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin Liver Dis 2004;8:521–533.
- Berasain C, Betes M, Panizo A, Ruiz J, Herrero JI, Civeira MP, Prieto J: Pathological and virological findings in patients with persistent hypertransaminasaemia of unknown aetiology. Gut 2000;47:429–435.
- Marcos A, Fisher RA, Ham JM, Shiffman ML, Sanyal AJ, Luketic VA, Sterling RK, Fulcher AS, Posner MP: Liver regeneration and function in donor and recipient after right lobe adult to adult living donor liver transplantation. Transplantation 2000;69: 1375–1379.
- Hwang S, Lee SG, Jang SJ, Cho SH, Kim KH, Ahn CS, Moon DB, Ha TY: The effect of donor weight reduction on hepatic steatosis for living donor liver transplantation. Liver Transpl 2004;10:721–725.
- Dixon JB, Bhathal PS, O’Brien PE: Nonalcoholic fatty liver disease: predictors of non-alcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 2001; 121:91–100.
- Marceau P: Contribution of bariatric surgery to the comprehension of morbid obesity. Obes Surg 2005;15:3–10.
- Del Gaudio A, Boschi L, Del Gaudio GA, Mastrangelo L, Munari D: Liver damage in obese patients. Obes Surg 2002;12:802–804.
- Luyckx FH, Desaive C, Thiry A, Dewé W, Scheen AJ, Gielen JE, Lefèbvre PJ: Liver abnormalities in severely obese subjects: effect of drastic weight loss after gastroplasty. Int J Obes Relat Metab Disord 1998;22:222–226.
- Silverman JF, O’Brien KF, Long S, Leggett N, Khazanie PG, Pories WJ, Norris HT, Caro JF: Liver pathology in morbidly obese patients with and without diabetes. Am J Gastroenterol 1990;85:1349–1355.
- Kral JG: Patient selection for treatment of obesity. Surg Obes Relat Dis 2005;1:126–132.
- Bellentani S, Saccoccio G, Masutti F, Crocè LS, Brandi G, Sasso F, Cristanini G, Tiribelli C: Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 2000;132:112–117.
- Bellentani S, Bedogni G, Miglioli L, Tiribelli C: The epidemiology of fatty liver. Eur J Gastroenterol Hepatol 2004;16:1087–1093.
- Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S: Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos Nutrition and Liver Study. Hepatology 2005;42:44–52.
Nomura H, Kashiwagi S, Hayashi J, Kajiyama W, Tani S, Goto M: Prevalence of fatty liver in a general population of Okinawa, Japan. Jpn J Med 1988;27:521–528.
- Lonardo A, Bellini M, Tartoni P, Tondelli E: The bright liver syndrome. Prevalence and determinants of a ‘bright’ liver echopattern. Ital J Gastroenterol Hepatol 1997;29:351–356.
- Omagari K, Kadokawa Y, Masuda J, et al: Fatty liver in non-alcoholic non-overweight Japanese adults: incidence and clinical characteristics. J Gastroenterol Hepatol 2002; 17:1098–1105.
- Araujo LM, De Oliveira DA, Nunes DS: Liver and biliary ultrasonography in diabetic and non-diabetic obese women. Diabetes Metab 1998;24:458–462.
- Radu C, Grigorescu M, Crisan D, Lupsor M, Constantin D, Dina L: Prevalence and associated risk factors of non-alcoholic fatty liver disease in hospitalized patients. J Gastrointestin Liver Dis 2008;17:255–260.
- El-Hassan AY, Ibrahim EM, al-Mulhim FA, Nabhan AA, Chammas MY: Fatty infiltration of the liver: analysis of prevalence, radiological and clinical features and influence on patient management. Br J Radiol 1992;65:774–778.
- Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH: Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40:1387–1395.
- Patt CH, Yoo HY, Dibadj K, Flynn J, Thuluvath PJ: Prevalence of transaminase abnormalities in asymptomatic, healthy subjects participating in an executive health-screening program. Dig Dis Sci 2003;48:797–801.
- Ong JP, Younossi ZM: Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis 2007;11:1–16, vii.
- Nonomura A, Mizukami Y, Unoura M, Kobayashi K, Takeda Y, Takeda R: Clinicopathologic study of alcohol-like liver disease in non-alcoholics; non-alcoholic steatohepatitis and fibrosis. Gastroenterol Jpn 1992;27:521–528.
- Ikai E, Ishizaki M, Suzuki Y, Ishida M, Noborizaka Y, Yamada Y: Association between hepatic steatosis, insulin resistance and hyperinsulinaemia as related to hypertension in alcohol consumers and obese people. J Hum Hypertens 1995;9:101–105.
- Kawai N, Tsugaya M, Sakagami H, Sasaki S, Kohri K: A study of the indication for conservative surgery in adult hydronephrosis based on presurgery post-contrast computed tomography (CT) finding (in Japanese). Nippon Hinyokika Gakkai Zasshi 1997;88:997–1004.
- Tazawa Y, Noguchi H, Nishinomiya F, Takada G: Effect of weight changes on serum transaminase activities in obese children. Acta Paediatr Jpn 1997;39:210–214.
- Rashid M, Roberts EA: Nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr 2000;30:48–53.
- Browning JD: Statins and hepatic steatosis: perspectives from the Dallas Heart Study. Hepatology 2006;44:466–471.
- Bacon BR, Farahvash MJ, Janney CG, Neuschwander-Tetri BA: Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology 1994;107:1103–1109.
- Powell EE, Cooksley WG, Hanson R, Searle J, Halliday JW, Powell LW: The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology 1990;11:74–80.
- Frith J, Day CP, Henderson E, Burt AD, Newton JL: Non-alcoholic fatty liver disease in older people. Gerontology 2009;55:607–613.
- Ludwig J, Viggiano TR, McGill DB, Oh BJ: Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980;55:434–438.
- Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ: Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999;116:1413–1419.
- Diehl AM, Goodman Z, Ishak KG: Alcohollike liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury. Gastroenterology 1988;95:1056–1062.
- Lee RG: Nonalcoholic steatohepatitis: a study of 49 patients. Hum Pathol 1989;20:594–598.
- AGA technical review on nonalcoholic fatty liver disease. Gastroenterology 2002;123: 1705–1725.
- Clark JM, Diehl AM: Defining nonalcoholic fatty liver disease: implications for epidemiologic studies. Gastroenterology 2003;124:248–250.
- Lonardo A, Loria P, Leonardi F, Borsatti A, Neri P, Pulvirenti M, Verrone AM, Bagni A, Bertolotti M, Ganazzi D, Carulli N, POLI.ST.E.N.A. Study Group: Policentrica Steatosi Epatica Non Alcolica. Fasting insulin and uric acid levels but not indices of iron metabolism are independent predictors of non-alcoholic fatty liver disease. A case-control study. Dig Liver Dis 2002;34:204–211.
- Fargion S, Mattioli M, Fracanzani AL, Sampietro M, Tavazzi D, Fociani P, Taioli E, Valenti L, Fiorelli G: Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis. Am J Gastroenterol 2001;96:2448–2455.
- Skelly MM, James PD, Ryder SD: Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J Hepatol 2001;35:195–199.
- Mofrad P, Contos MJ, Haque M, Sargeant C, Fisher RA, Luketic VA, Sterling RK, Shiffman ML, Stravitz RT, Sanyal AJ: Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 2003;37:1286–1292.
- Daniel S, Ben-Menachem T, Vasudevan G, Ma CK, Blumenkehl M: Prospective evaluation of unexplained chronic liver transaminase abnormalities in asymptomatic and symptomatic patients. Am J Gastroenterol 1999;94:3010–3014.
- Hilden M, Christoffersen P, Juhl E, Dalgaard JB: Liver histology in a ‘normal’ population – examinations of 503 consecutive fatal traffic casualties. Scand J Gastroenterol 1977;12:593–597.
- Hultcrantz R, Glaumann H, Lindberg G, Nilsson LH: Liver investigation in 149 asymptomatic patients with moderately elevated activities of serum aminotransferases. Scand J Gastroenterol 1986;21:109–113.
- Angulo P, Keach JC, Batts KP, Lindor KD: Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999;30:1356–1362.
- Dixon JB, Bhathal PS, O’Brien PE: Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 2001;121:91–100.
- Ong J, Younossi ZM, Reddy V, Price LL, Gramlich T, Mayes J, Boparai N: Cryptogenic cirrhosis and post-transplantation nonalcoholic fatty liver disease. Liver Transpl 2001;7:797–801.
- Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, Tiribelli C: The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol 2006;6:33.
- Gastaldelli A, Kozakova M, Højlund K, Flyvbjerg A, Favuzzi A, Mitrakou A, Balkau B, RISC Investigators: Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population. Hepatology 2009;49:1537–1544.
- Alberti KG, Zimmet P, Shaw J, IDF Epidemiology Task Force Consensus Group: The metabolic syndrome – a new worldwide definition. Lancet 2005;366:1059–1062.
- Ong JP, Pitts A, Younossi ZM: Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol 2008;49:608–612.
- Schindhelm RK, Dekker JM, Nijpels G, Stehouwer CD, Bouter LM, Heine RJ, et al: Alanine aminotransferase predicts coronary heart disease events: a 10-year follow-up of the Hoorn study. Atherosclerosis 2007;191:391–396.
- Goessling W, Massaro JM, Vasan RS, D’Agostino RB Sr, Ellison RC, Fox CS: Aminotransferase levels and 20-year risk of metabolic syndrome, diabetes, and cardiovascular disease. Gastroenterology 2008;135:1935–1944.
Targher G, Bertolini L, Tessari R, Zenari L, Arcaro G: The International Diabetes Federation definition of the metabolic syndrome independently predicts future cardiovascular events in Type 2 diabetic patients. The Valpolicella Heart Diabetes Study. Diabet Med 2006;23:1270–1271.
- Bedogni G, Miglioli L, Masutti F, Castiglione A, Crocè LS, Tiribelli C, Bellentani S: Incidence and natural course of fatty liver in the general population: the Dionysos study. Hepatology 2007;46:1387–1391.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.