Epidemiology of Non-Alcoholic Fatty Liver Disease

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.

[1]  R. Hanson,et al.  The natural history of nonalcoholic steatohepatitis: A follow‐up study of forty‐two patients for up to 21 years , 1990, Hepatology.

[2]  J. Silverman,et al.  Liver pathology in morbidly obese patients with and without diabetes. , 1990, The American journal of gastroenterology.

[3]  S. Bellentani,et al.  Hepatology Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD) , 2009 .

[4]  Beverley Balkau,et al.  Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population , 2009, Hepatology.

[5]  P. D. James,et al.  Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. , 2001, Journal of hepatology.

[6]  B. Neuschwander‐Tetri,et al.  Nonalcoholic steatohepatitis: Summary of an AASLD Single Topic Conference , 2003, Hepatology.

[7]  A. Feldstein,et al.  Lipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equal , 2009, Expert review of gastroenterology & hepatology.

[8]  G. Targher,et al.  The International Diabetes Federation definition of the metabolic syndrome independently predicts future cardiovascular events in Type 2 diabetic patients. The Valpolicella Heart Diabetes Study , 2006, Diabetic medicine : a journal of the British Diabetic Association.

[9]  A. McCullough,et al.  The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. , 2004, Clinics in liver disease.

[10]  G. Bedogni,et al.  Fatty liver: how frequent is it and why? , 2004, Annals of hepatology.

[11]  Kenichi Kobayashi,et al.  Clinicopathologic study of alcohol-like liver disease in non-alcoholics; non-alcoholic steatohepatitis and fibrosis , 1992, Gastroenterologia Japonica.

[12]  W. Goessling,et al.  Aminotransferase levels and 20-year risk of metabolic syndrome, diabetes, and cardiovascular disease. , 2008, Gastroenterology.

[13]  G. Marchesini,et al.  Association of nonalcoholic fatty liver disease with insulin resistance. , 1999, The American journal of medicine.

[14]  K. Ishak,et al.  Alcohollike liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury. , 1988, Gastroenterology.

[15]  S. Caldwell,et al.  The spectrum expanded: cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease. , 2004, Journal of hepatology.

[16]  Z. Younossi,et al.  6 NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS ASSOCIATED WITH HIGHER OVERALL MORTALITY AND LIVER RELATED MORTALITY , 2008 .

[17]  E. Roberts,et al.  Nonalcoholic steatohepatitis in children , 2003, Current gastroenterology reports.

[18]  A. Lonardo,et al.  Review article: hepatic steatosis and insulin resistance , 2005, Alimentary pharmacology & therapeutics.

[19]  R. Hultcrantz,et al.  Liver investigation in 149 asymptomatic patients with moderately elevated activities of serum aminotransferases. , 1986, Scandinavian journal of gastroenterology.

[20]  M. Ishizaki,et al.  Association between hepatic steatosis, insulin resistance and hyperinsulinaemia as related to hypertension in alcohol consumers and obese people. , 1995, Journal of human hypertension.

[21]  F. Schaffner,et al.  Nonalcoholic fatty liver disease. , 1986, Progress in liver diseases.

[22]  G. Bedogni,et al.  The epidemiology of fatty liver , 2004, European journal of gastroenterology & hepatology.

[23]  G. Bedogni,et al.  Prevalence of and risk factors for nonalcoholic fatty liver disease: The Dionysos nutrition and liver study , 2005, Hepatology.

[24]  T. Ben-Menachem,et al.  Prospective evaluation of unexplained chronic liver transaminase abnormalities in asymptomatic and symptomatic patients , 1999, American Journal of Gastroenterology.

[25]  Z. Younossi,et al.  Cryptogenic cirrhosis and posttransplantation nonalcoholic fatty liver disease , 2001, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[26]  L. N. Valenti,et al.  Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis , 2001, American Journal of Gastroenterology.

[27]  J. Browning Statins and hepatic steatosis: Perspectives from the Dallas Heart Study , 2006, Hepatology.

[28]  A. Lonardo,et al.  NAFLD and Cardiovascular Risk: Direct Evidence for the Tale of Two Ages , 2009, The American Journal of Gastroenterology.

[29]  F. Al-Mulhim,et al.  Fatty infiltration of the liver: analysis of prevalence, radiological and clinical features and influence on patient management. , 1992, The British journal of radiology.

[30]  H. Yoo,et al.  Prevalence of Transaminase Abnormalities in Asymptomatic, Healthy Subjects Participating in an Executive Health-Screening Program , 2003, Digestive Diseases and Sciences.

[31]  Hirokazu Takahashi,et al.  Dysfunctional very‐low‐density lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis , 2009, Hepatology.

[32]  G. Marchesini,et al.  Clinical Features and Natural History of Nonalcoholic Steatosis Syndromes , 2001, Seminars in liver disease.

[33]  L. Bouter,et al.  Alanine aminotransferase predicts coronary heart disease events: a 10-year follow-up of the Hoorn Study. , 2007, Atherosclerosis.

[34]  J. Ludwig,et al.  Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. , 1980, Mayo Clinic proceedings.

[35]  R. Fisher,et al.  Liver regeneration and function in donor and recipient after right lobe adult to adult living donor liver transplantation. , 2000, Transplantation.

[36]  Z. Younossi,et al.  Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. , 2008, Journal of hepatology.

[37]  Z. Younossi,et al.  Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. , 1999, Gastroenterology.

[38]  D. Nunes,et al.  Liver and biliary ultrasonography in diabetic and non-diabetic obese women. , 1998, Diabetes & metabolism.

[39]  J. Dixon,et al.  Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. , 2001, Gastroenterology.

[40]  K. Batts,et al.  Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis , 1999, Hepatology.

[41]  Ground Ke Liver pathology in aircrew. , 1982 .

[42]  P. Christoffersen,et al.  Liver histology in a 'normal' population--examinations of 503 consecutive fatal traffic casualties. , 1977, Scandinavian journal of gastroenterology.

[43]  M. Lupsor,et al.  Prevalence and associated risk factors of non-alcoholic fatty liver disease in hospitalized patients. , 2008, Journal of gastrointestinal and liver diseases : JGLD.

[44]  Anna Castiglione,et al.  The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population , 2006, BMC gastroenterology.

[45]  Jonathan C. Cohen,et al.  Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity , 2004, Hepatology.

[46]  S. Jang,et al.  The effect of donor weight reduction on hepatic steatosis for living donor liver transplantation , 2004, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[47]  I. Wanless,et al.  Fatty liver hepatitis (steatohepatitis) and obesity: An autopsy study with analysis of risk factors , 1990, Hepatology.

[48]  Hajime Isomoto,et al.  Fatty liver in non‐alcoholic non‐overweight Japanese adults: Incidence and clinical characteristics , 2002, Journal of gastroenterology and hepatology.

[49]  K. Tsuneyama,et al.  Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin‐3 knockout mice , 2008, Hepatology research : the official journal of the Japan Society of Hepatology.

[50]  G. Chejfec,et al.  Does nonalcoholic fatty liver disease predispose patients to hepatocellular carcinoma in the absence of cirrhosis? , 2008, Archives of pathology & laboratory medicine.

[51]  S. Bellentani,et al.  Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD). , 2009, Annals of hepatology.

[52]  J. Prieto,et al.  Pathological and virological findings in patients with persistent hypertransaminasaemia of unknown aetiology , 2000, Gut.

[53]  Randall G. Lee,et al.  Nonalcoholic steatohepatitis: a study of 49 patients. , 1989, Human pathology.

[54]  A. Lonardo,et al.  Should Nonalcoholic Fatty Liver Disease Be Renamed? , 2005, Digestive Diseases.

[55]  G. Del Gaudio,et al.  Liver Damage in Obese Patients , 2002, Obesity surgery.

[56]  Jeanne M Clark,et al.  Defining nonalcoholic fatty liver disease: implications for epidemiologic studies. , 2003, Gastroenterology.

[57]  K. Kohri,et al.  [A study of the indication for conservative surgery in adult hydronephrosis based on presurgery post-contrast computed tomography (CT) finding]. , 1997, Nihon Hinyokika Gakkai zasshi. The japanese journal of urology.

[58]  A. Scheen,et al.  Liver abnormalities in severely obese subjects: Effect of drastic weight loss after gastroplasty , 1998, International Journal of Obesity.

[59]  R. Fisher,et al.  Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values , 2003, Hepatology.

[60]  Paul Zimmet,et al.  The metabolic syndrome—a new worldwide definition , 2005, The Lancet.

[61]  B. Neuschwander‐Tetri,et al.  Nonalcoholic steatohepatitis: an expanded clinical entity. , 1994, Gastroenterology.

[62]  Z. Younossi,et al.  Epidemiology and natural history of NAFLD and NASH. , 2007, Clinics in liver disease.

[63]  A. Graham Curcumin adds spice to the debate: lipid metabolism in liver disease , 2009, British journal of pharmacology.

[64]  G. Brandi,et al.  Prevalence of and Risk Factors for Hepatic Steatosis in Northern Italy , 2000, Annals of Internal Medicine.

[65]  H. Nomura,et al.  Prevalence of fatty liver in a general population of Okinawa, Japan. , 1988, Japanese journal of medicine.

[66]  M. Bellini,et al.  The bright liver syndrome. Prevalence and determinants of a "bright" liver echopattern. , 1997, Italian journal of gastroenterology and hepatology.

[67]  J. Kral Patient selection for treatment of obesity. , 2005, Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery.

[68]  A. Sanyal,et al.  AGA technical review on nonalcoholic fatty liver disease. , 2002, Gastroenterology.

[69]  P. Marceau Contribution of Bariatric Surgery to the Comprehension of Morbid Obesity , 2005, Obesity surgery.

[70]  P. Gosling DORLAND’S ILLUSTRATED MEDICAL DICTIONARY , 2003, Australasian Chiropractic & Osteopathy.

[71]  K. Lindor,et al.  Non‐alcoholic fatty liver disease , 2002, Journal of gastroenterology and hepatology.

[72]  K. E. Ground Liver pathology in aircrew. , 1982, Aviation, space, and environmental medicine.

[73]  G. Marchesini,et al.  Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome , 2003, Hepatology.

[74]  J. Newton,et al.  Non-Alcoholic Fatty Liver Disease in Older People , 2009, Gerontology.

[75]  Jeanne M Clark,et al.  Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis. , 2003, JAMA.

[76]  G. Bedogni,et al.  Incidence and natural course of fatty liver in the general population: The Dionysos study , 2007, Hepatology.