The Epidemiology of Nonalcoholic Fatty Liver Disease: A Global Perspective

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver disease in the United States and worldwide. With obesity being an important risk factor universally, NAFLD is now receiving greater attention and is regarded as a public health issue. In addition, as a result of an aging population and the improving control of other major causes of chronic liver disease, such as hepatitis C and hepatitis B, the burden of NAFLD is expected to increase in years to come. Prevalence estimates of this disease vary widely across populations because of differences in methods for diagnosis and/or definition. New strategies for the prevention, diagnosis, and management will be required to alter the course of this disease.

KEYWORDS

Nonalcoholic fatty liver disease - NAFLD - epidemiology - risk factors

REFERENCES

• 1 Brunt E M. Nonalcoholic steatohepatitis.  Semin Liver Dis. 2004;  24(1) 3-20
• 2 Bugianesi E, Leone N, Vanni E et al.. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma.  Gastroenterology. 2002;  123(1) 134-140
• 3 Clark J M, Diehl A M. Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis.  JAMA. 2003;  289(22) 3000-3004
• 4 Abdelmalek M F, Diehl A M. Nonalcoholic fatty liver disease as a complication of insulin resistance.  Med Clin North Am. 2007;  91(6) 1125-1149 , ix
• 5 Brunt E M. Nonalcoholic steatohepatitis: pathologic features and differential diagnosis.  Semin Diagn Pathol. 2005;  22(4) 330-338
• 6 Ogden C L, Carroll M D, Curtin L R, McDowell M A, Tabak C J, Flegal K M. Prevalence of overweight and obesity in the United States, 1999–2004.  JAMA. 2006;  295(13) 1549-1555
• 7 Clark J M. The epidemiology of nonalcoholic fatty liver disease in adults.  J Clin Gastroenterol. 2006;  40(suppl 1) S5-S10
• 8 Falck-Ytter Y, Younossi Z M, Marchesini G, McCullough A J. Clinical features and natural history of nonalcoholic steatosis syndromes.  Semin Liver Dis. 2001;  21(1) 17-26
• 9 Neuschwander-Tetri B A, Caldwell S H. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference.  Hepatology. 2003;  37(5) 1202-1219
• 10 Yeh M M, Brunt E M. Pathology of nonalcoholic fatty liver disease.  Am J Clin Pathol. 2007;  128(5) 837-847
• 11 Ratziu V, Charlotte F, Heurtier A et al.. Sampling variability of liver biopsy in nonalcoholic fatty liver disease.  Gastroenterology. 2005;  128(7) 1898-1906
• 12 Mofrad P, Contos M J, Haque M et al.. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values.  Hepatology. 2003;  37(6) 1286-1292
• 13 Yano E, Tagawa K, Yamaoka K, Mori M. Test validity of periodic liver function tests in a population of Japanese male bank employees.  J Clin Epidemiol. 2001;  54(9) 945-951
• 14 Lazo M, Selvin E, Clark J M. Brief Communication: Clinical implications of short-term variability in liver function test results.  Ann Intern Med. 2008;  148 348-352
• 15 Clark J M, Brancati F L, Diehl A M. Nonalcoholic fatty liver disease.  Gastroenterology. 2002;  122(6) 1649-1657
• 16 Strauss S, Gavish E, Gottlieb P, Katsnelson L. Interobserver and intraobserver variability in the sonographic assessment of fatty liver.  AJR Am J Roentgenol. 2007;  189(6) W320-W323
• 17 Szczepaniak L S, Nurenberg P, Leonard D et al.. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population.  Am J Physiol Endocrinol Metab. 2005;  288(2) E462-E468
• 18 Clouston A D, Jonsson J R, Powell E E. Steatosis as a cofactor in other liver diseases: hepatitis C virus, alcohol, hemochromatosis, and others.  Clin Liver Dis. 2007;  11(1) 173-189 , x
• 19 Adinolfi L E, Gambardella M, Andreana A, Tripodi M F, Utili R, Ruggiero G. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity.  Hepatology. 2001;  33(6) 1358-1364
• 20 Friedenberg F, Pungpapong S, Zaeri N, Braitman L E. The impact of diabetes and obesity on liver histology in patients with hepatitis C.  Diabetes Obes Metab. 2003;  5(3) 150-155
• 21 Lonardo A, Adinolfi L E, Loria P, Carulli N, Ruggiero G, Day C P. Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extrahepatic disease.  Gastroenterology. 2004;  126(2) 586-597
• 22 Patton H M, Patel K, Behling C et al.. The impact of steatosis on disease progression and early and sustained treatment response in chronic hepatitis C patients.  J Hepatol. 2004;  40(3) 484-490
• 23 Pekow J R, Bhan A K, Zheng H, Chung R T. Hepatic steatosis is associated with increased frequency of hepatocellular carcinoma in patients with hepatitis C-related cirrhosis.  Cancer. 2007;  109(12) 2490-2496
• 24 Ramesh S, Sanyal A J. Hepatitis C and nonalcoholic fatty liver disease.  Semin Liver Dis. 2004;  24(4) 399-413
• 25 Leandro G, Mangia A, Hui J et al.. Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data.  Gastroenterology. 2006;  130(6) 1636-1642
• 26 Thomopoulos K C, Arvaniti V, Tsamantas A C et al.. Prevalence of liver steatosis in patients with chronic hepatitis B: a study of associated factors and of relationship with fibrosis.  Eur J Gastroenterol Hepatol. 2006;  18(3) 233-237
• 27 Hadigan C, Liebau J, Andersen R, Holalkere N S, Sahani D V. Magnetic resonance spectroscopy of hepatic lipid content and associated risk factors in HIV infection.  J Acquir Immune Defic Syndr. 2007;  46(3) 312-317
• 28 Clouston A D, Powell E E. Interaction of non-alcoholic fatty liver disease with other liver diseases.  Best Pract Res Clin Gastroenterol. 2002;  16(5) 767-781
• 29 Zhou Y J, Li Y Y, Nie Y Q et al.. Prevalence of fatty liver disease and its risk factors in the population of South China.  World J Gastroenterol. 2007;  13(47) 6419-6424
• 30 Fan J G, Li F, Cai X B, Peng Y D, Ao Q H, Gao Y. The importance of metabolic factors for the increasing prevalence of fatty liver in Shanghai factory workers.  J Gastroenterol Hepatol. 2007;  22(5) 663-668
• 31 Lin T J, Lin C L, Wang C S, Liu S O, Liao L Y. Prevalence of HFE mutations and relation to serum iron status in patients with chronic hepatitis C and patients with nonalcoholic fatty liver disease in Taiwan.  World J Gastroenterol. 2005;  11(25) 3905-3908
• 32 Fan J G, Zhu J, Li X J et al.. Prevalence of and risk factors for fatty liver in a general population of Shanghai, China.  J Hepatol. 2005;  43(3) 508-514
• 33 Shen L, Fan J G, Shao Y et al.. Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai: an epidemiological survey.  World J Gastroenterol. 2003;  9(5) 1106-1110
• 34 Zelber-Sagi S, Nitzan-Kaluski D, Halpern Z, Oren R. Prevalence of primary non-alcoholic fatty liver disease in a population-based study and its association with biochemical and anthropometric measures.  Liver Int. 2006;  26(7) 856-863
• 35 Kagansky N, Levy S, Keter D et al.. Non-alcoholic fatty liver disease: a common and benign finding in octogenarian patients.  Liver Int. 2004;  24(6) 588-594
• 36 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(1) 44-52
• 37 Hamaguchi M, Kojima T, Takeda N et al.. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease.  Ann Intern Med. 2005;  143(10) 722-728
• 38 Jimba S, Nakagami T, Takahashi M et al.. Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults.  Diabet Med. 2005;  22(9) 1141-1145
• 39 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(10) 1098-1105
• 40 Kim H J, Kim H J, Lee K E et al.. Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults.  Arch Intern Med. 2004;  164(19) 2169-2175
• 41 Lizardi-Cervera J, Laparra D I, Chavez-Tapia N C, Ostos M E, Esquivel M U. Prevalence of NAFLD and metabolic syndrome in asymtomatics subjects.  Rev Gastroenterol Mex. 2006;  71(4) 453-459
• 42 Chen C H, Huang M H, Yang J C et al.. Prevalence and risk factors of nonalcoholic fatty liver disease in an adult population of Taiwan: metabolic significance of nonalcoholic fatty liver disease in nonobese adults.  J Clin Gastroenterol. 2006;  40(8) 745-752
• 43 Park S H, Jeon W K, Kim S H et al.. Prevalence and risk factors of non-alcoholic fatty liver disease among Korean adults.  J Gastroenterol Hepatol. 2006;  21(1) 138-143
• 44 Lin Y C, Lo H M, Chen J D. Sonographic fatty liver, overweight and ischemic heart disease.  World J Gastroenterol. 2005;  11(31) 4838-4842
• 45 Church T S, Kuk J L, Ross R, Priest E L, Biltoft E, Blair S N. Association of cardiorespiratory fitness, body mass index, and waist circumference to nonalcoholic fatty liver disease.  Gastroenterology. 2006;  130(7) 2023-2030
• 46 Browning J D, Szczepaniak L S, Dobbins R et al.. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity.  Hepatology. 2004;  40(6) 1387-1395
• 47 Pendino G M, Mariano A, Surace P et al.. Prevalence and etiology of altered liver tests: a population-based survey in a Mediterranean town.  Hepatology. 2005;  41(5) 1151-1159
• 48 Suzuki A, Angulo P, Lymp J et al.. Chronological development of elevated aminotransferases in a nonalcoholic population.  Hepatology. 2005;  41(1) 64-71
• 49 Clark J M, Brancati F L, Diehl A M. The prevalence and etiology of elevated aminotransferase levels in the United States.  Am J Gastroenterol. 2003;  98(5) 960-967
• 50 Ruhl C E, Everhart J E. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States.  Gastroenterology. 2003;  124(1) 71-79
• 51 Amarapurkar A, Ghansar T. Fatty liver: experience from western India.  Ann Hepatol. 2007;  6(1) 37-40
• 52 Yamamoto K, Takada Y, Fujimoto Y et al.. Nonalcoholic steatohepatitis in donors for living donor liver transplantation.  Transplantation. 2007;  83(3) 257-262
• 53 Brunt E M, Janney C G, Di Bisceglie A M et al.. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions.  Am J Gastroenterol. 1999;  94 2467-2474
• 54 Halon A, Patrzalek D, Rabczynski J. Hepatic steatosis in liver transplant donors: rare phenomenon or common feature of donor population?.  Transplant Proc. 2006;  38(1) 193-195
• 55 Tran T T, Changsri C, Shackleton C R et al.. Living donor liver transplantation: histological abnormalities found on liver biopsies of apparently healthy potential donors.  J Gastroenterol Hepatol. 2006;  21(2) 381-383
• 56 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(10) 1098-1105
• 57 Bedogni G, Miglioli L, Masutti F et al.. Incidence and natural course of fatty liver in the general population: the Dionysos study.  Hepatology. 2007;  46(5) 1387-1391
• 58 Ground K E. Liver pathology in aircrew.  Aviat Space Environ Med. 1982;  53(1) 14-18
• 59 Underwood Ground K E. Prevalence of fatty liver in healthy male adults accidentally killed.  Aviat Space Environ Med. 1984;  55(1) 59-61
• 60 Hilden M, Christoffersen P, Juhl E, Dalgaard J B. Liver histology in a “normal” population: examinations of 503 consecutive fatal traffic casualties.  Scand J Gastroenterol. 1977;  12(5) 593-597
• 61 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
• 62 Angelico F, Del B M, Conti R et al.. Insulin resistance, the metabolic syndrome, and nonalcoholic fatty liver disease.  J Clin Endocrinol Metab. 2005;  90(3) 1578-1582
• 63 Gupte P, Amarapurkar D, Agal S et al.. Non-alcoholic steatohepatitis in type 2 diabetes mellitus.  J Gastroenterol Hepatol. 2004;  19(8) 854-858
• 64 Roesch-Dietlen F, Dorantes-Cuellar A, Carrillo-Toledo M G et al.. Frequency of NAFLD in a group of patients with metabolic syndrome in Veracruz, Mexico.  Rev Gastroenterol Mex. 2006;  71(4) 446-452
• 65 Gambarin-Gelwan M, Kinkhabwala S V, Schiano T D, Bodian C, Yeh H C, Futterweit W. Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome.  Clin Gastroenterol Hepatol. 2007;  5(4) 496-501
• 66 Weston S R, Leyden W, Murphy R et al.. Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease.  Hepatology. 2005;  41(2) 372-379
• 67 Liangpunsakul S, Chalasani N. Unexplained elevations in alanine aminotransferase in individuals with the metabolic syndrome: results from the third National Health and Nutrition Survey (NHANES III).  Am J Med Sci. 2005;  329(3) 111-116
• 68 Lima M L, Mourao S C, Diniz M T, Leite V H. Hepatic histopathology of patients with morbid obesity submitted to gastric bypass.  Obes Surg. 2005;  15(5) 661-669
• 69 de Oliveira C P, de Mello E S, Alves V A, Saviero S M, Strauss E. Changes in histological criteria lead to different prevalences of nonalcoholic steatohepatitis in severe obesity.  Ann Hepatol. 2007;  6(4) 255-261
• 70 Boza C, Riquelme A, Ibanez L et al.. Predictors of nonalcoholic steatohepatitis (NASH) in obese patients undergoing gastric bypass.  Obes Surg. 2005;  15(8) 1148-1153
• 71 Harnois F, Msika S, Sabate J M et al.. Prevalence and predictive factors of non-alcoholic steatohepatitis (NASH) in morbidly obese patients undergoing bariatric surgery.  Obes Surg. 2006;  16(2) 183-188
• 72 Wolf A M, Busch B, Kuhlmann H W, Beisiegel U. Histological changes in the liver of morbidly obese patients: correlation with metabolic parameters.  Obes Surg. 2005;  15(2) 228-237
• 73 Papadia F S, Marinari G M, Camerini G et al.. Liver damage in severely obese patients: a clinical-biochemical-morphologic study on 1,000 liver biopsies.  Obes Surg. 2004;  14(7) 952-958
• 74 Sorrentino P, Tarantino G, Conca P et al.. Silent non-alcoholic fatty liver disease: a clinical-histological study.  J Hepatol. 2004;  41(5) 751-757
• 75 Chavarria-Arciniega S, Lopez-Alvarenga J C, Uribe-Uribe N O, Herrera-Hernandez M, Gonzalez-Barranco J. Relationship between morphological diagnosis of NASH (non-alcoholic steatohepatitis) and liver function tests in a group of patients with morbid obesity.  Rev Invest Clin. 2005;  57(4) 505-512
• 76 Liew P L, Lee W J, Lee Y C, Wang H H, Wang W, Lin Y C. Hepatic histopathology of morbid obesity: concurrence of other forms of chronic liver disease.  Obes Surg. 2006;  16(12) 1584-1593
• 77 Kleiner D E, Brunt E M, Van Natta M et al.. Design and validation of a histological scoring system for nonalcoholic fatty liver disease.  Hepatology. 2005;  41 1313-1321
• 78 Gholam P M, Flancbaum L, Machan J T, Charney D A, Kotler D P. Nonalcoholic fatty liver disease in severely obese subjects.  Am J Gastroenterol. 2007;  102(2) 399-408
• 79 Solga S F, Clark J M, Alkhuraishi A R et al.. Race and comorbid factors predict nonalcoholic fatty liver disease histopathology in severely obese patients.  Surg Obes Relat Dis. 2005;  1(1) 6-11
• 80 Kunde S S, Lazenby A J, Clements R H, Abrams G A. Spectrum of NAFLD and diagnostic implications of the proposed new normal range for serum ALT in obese women.  Hepatology. 2005;  42(3) 650-656
• 81 Abrams G A, Kunde S S, Lazenby A J, Clements R H. Portal fibrosis and hepatic steatosis in morbidly obese subjects: a spectrum of nonalcoholic fatty liver disease.  Hepatology. 2004;  40(2) 475-483
• 82 Beymer C, Kowdley K V, Larson A, Edmonson P, Dellinger E P, Flum D R. Prevalence and predictors of asymptomatic liver disease in patients undergoing gastric bypass surgery.  Arch Surg. 2003;  138(11) 1240-1244
• 83 Spaulding L, Trainer T, Janiec D. Prevalence of non-alcoholic steatohepatitis in morbidly obese subjects undergoing gastric bypass.  Obes Surg. 2003;  13(3) 347-349
• 84 Ong J P, Elariny H, Collantes R et al.. Predictors of nonalcoholic steatohepatitis and advanced fibrosis in morbidly obese patients.  Obes Surg. 2005;  15(3) 310-315
• 85 Albano E, Mottaran E, Vidali M et al.. Immune response towards lipid peroxidation products as a predictor of progression of non-alcoholic fatty liver disease to advanced fibrosis.  Gut. 2005;  54(7) 987-993
• 86 Angelico F, Del B M, Conti R et al.. Insulin resistance, the metabolic syndrome, and nonalcoholic fatty liver disease.  J Clin Endocrinol Metab. 2005;  90(3) 1578-1582
• 87 Kelley D E, McKolanis T M, Hegazi R A, Kuller L H, Kalhan S C. Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance.  Am J Physiol Endocrinol Metab. 2003;  285(4) E906-E916
• 88 Kotronen A, Juurinen L, Hakkarainen A et al.. Liver fat is increased in type 2 diabetic patients and underestimated by serum alanine aminotransferase compared with equally obese nondiabetic subjects.  Diabetes Care. 2008;  31(1) 165-169
• 89 Guha I N, Parkes J, Roderick P R, Harris S, Rosenberg W M. Non-invasive markers associated with liver fibrosis in non-alcoholic fatty liver disease.  Gut. 2006;  55(11) 1650-1660
• 90 Angulo P, Keach J C, Batts K P, Lindor K D. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis.  Hepatology. 1999;  30(6) 1356-1362
• 91 Dixon J B, Bhathal P S, O'Brien P E. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese.  Gastroenterology. 2001;  121(1) 91-100
• 92 Mofrad P, Contos M J, Haque M et al.. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values.  Hepatology. 2003;  37(6) 1286-1292
• 93 Sheth S G, Gordon F D, Chopra S. Nonalcoholic steatohepatitis.  Ann Intern Med. 1997;  126(2) 137-145
• 94 Carulli L, Lonardo A, Lombardini S, Marchesini G, Loria P. Gender, fatty liver and GGT.  Hepatology. 2006;  44(1) 278-279
• 95 McKenzie J, Fisher B M, Jaap A J, Stanley A, Paterson K, Sattar N. Effects of HRT on liver enzyme levels in women with type 2 diabetes: a randomized placebo-controlled trial.  Clin Endocrinol (Oxf). 2006;  65(1) 40-44
• 96 Enzi G, Gasparo M, Biondetti P R, Fiore D, Semisa M, Zurlo F. Subcutaneous and visceral fat distribution according to sex, age, and overweight, evaluated by computed tomography.  Am J Clin Nutr. 1986;  44(6) 739-746
• 97 Lemieux S, Prud'homme D, Bouchard C, Tremblay A, Despres J P. Sex differences in the relation of visceral adipose tissue accumulation to total body fatness.  Am J Clin Nutr. 1993;  58(4) 463-467
• 98 Petersen K F, Befroy D, Dufour S et al.. Mitochondrial dysfunction in the elderly: possible role in insulin resistance.  Science. 2003;  300(5622) 1140-1142
• 99 Fink R I, Kolterman O G, Griffin J, Olefsky J M. Mechanisms of insulin resistance in aging.  J Clin Invest. 1983;  71(6) 1523-1535
• 100 Caldwell S H, Harris D M, Patrie J T, Hespenheide E E. Is NASH underdiagnosed among African Americans?.  Am J Gastroenterol. 2002;  97(6) 1496-1500
• 101 Caldwell S H, Ikura Y, Iezzoni J C, Liu Z. Has natural selection in human populations produced two types of metabolic syndrome (with and without fatty liver)?.  J Gastroenterol Hepatol. 2007;  22(suppl 1) S11-S19
• 102 Amarapurkar D N, Hashimoto E, Lesmana L A, Sollano J D, Chen P J, Goh K L. How common is non-alcoholic fatty liver disease in the Asia-Pacific region and are there local differences?.  J Gastroenterol Hepatol. 2007;  22(6) 788-793
• 103 Petersen K F, Dufour S, Feng J et al.. Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men.  Proc Natl Acad Sci U S A. 2006;  103(48) 18273-18277
• 104 Kotronen A, Yki-Jarvinen H. Fatty liver: a novel component of the metabolic syndrome.  Arterioscler Thromb Vasc Biol. 2008;  28(1) 27-38
• 105 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(2) 101-105
• 106 Kang H, Greenson J K, Omo J T et al.. Metabolic syndrome is associated with greater histologic severity, higher carbohydrate, and lower fat diet in patients with NAFLD.  Am J Gastroenterol. 2006;  101(10) 2247-2253
• 107 Marchesini G, Bugianesi E, Forlani G et al.. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome.  Hepatology. 2003;  37(4) 917-923
• 108 Jakobsen M U, Berentzen T, Sorensen T I, Overvad K. Abdominal obesity and fatty liver.  Epidemiol Rev. 2007;  29 77-87
• 109 Bellentani S, Bedogni G, Miglioli L, Tiribelli C. The epidemiology of fatty liver.  Eur J Gastroenterol Hepatol. 2004;  16(11) 1087-1093
• 110 Diehl A M. Hepatic complications of obesity.  Gastroenterol Clin North Am. 2005;  34(1) 45-61
• 111 Bellentani S, Saccoccio G, Masutti F et al.. Prevalence of and risk factors for hepatic steatosis in Northern Italy.  Ann Intern Med. 2000;  132(2) 112-117
• 112 Nair S, Mason A, Eason J, Loss G, Perrillo R P. Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis?.  Hepatology. 2002;  36(1) 150-155
• 113 Norman D, Bardwell W A, Arosemena F et al.. Serum aminotransferase levels are associated with markers of hypoxia in patients with obstructive sleep apnea.  Sleep. 2008;  31(1) 121-126
• 114 Kallwitz E R, Herdegen J, Madura J, Jakate S, Cotler S J. Liver enzymes and histology in obese patients with obstructive sleep apnea.  J Clin Gastroenterol. 2007;  41(10) 918-921
• 115 Acarturk G, Unlu M, Yuksel S, Albayrak R, Koken T, Peker Y. Obstructive sleep apnoea, glucose tolerance and liver steatosis in obese women.  J Int Med Res. 2007;  35(4) 458-466
• 116 Singh H, Pollock R, Uhanova J, Kryger M, Hawkins K, Minuk G Y. Symptoms of obstructive sleep apnea in patients with nonalcoholic fatty liver disease.  Dig Dis Sci. 2005;  50(12) 2338-2343
• 117 Savransky V, Nanayakkara A, Vivero A et al.. Chronic intermittent hypoxia predisposes to liver injury.  Hepatology. 2007;  45(4) 1007-1013
• 118 Zamora-Valdes D, Mendez-Sanchez N. Experimental evidence of obstructive sleep apnea syndrome as a second hit accomplice in nonalcoholic steatohepatitis pathogenesis.  Ann Hepatol. 2007;  6(4) 281-283
• 119 Tanne F, Gagnadoux F, Chazouilleres O et al.. Chronic liver injury during obstructive sleep apnea.  Hepatology. 2005;  41(6) 1290-1296
• 120 Abdelmalek M F, Liu C, Shuster J, Nelson D R, Asal N R. Familial aggregation of insulin resistance in first-degree relatives of patients with nonalcoholic fatty liver disease.  Clin Gastroenterol Hepatol. 2006;  4(9) 1162-1169
• 121 Willner I R, Waters B, Patil S R, Reuben A, Morelli J, Riely C A. Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease.  Am J Gastroenterol. 2001;  96(10) 2957-2961
• 122 Browning J D, Kumar K S, Saboorian M H, Thiele D L. Ethnic differences in the prevalence of cryptogenic cirrhosis.  Am J Gastroenterol. 2004;  99(2) 292-298
• 123 Struben V M, Hespenheide E E, Caldwell S H. Nonalcoholic steatohepatitis and cryptogenic cirrhosis within kindreds.  Am J Med. 2000;  108(1) 9-13
• 124 Wilfred de Alwis N M, Day C P. Genetics of alcoholic liver disease and nonalcoholic fatty liver disease.  Semin Liver Dis. 2007;  27(1) 44-54
• 125 Day C P. The potential role of genes in nonalcoholic fatty liver disease.  Clin Liver Dis. 2004;  8(3) 673-691
• 126 Cave M, Deaciuc I, Mendez C et al.. Nonalcoholic fatty liver disease: predisposing factors and the role of nutrition.  J Nutr Biochem. 2007;  18(3) 184-195
• 127 Jenkins D J, Josse A R, Labelle R, Marchie A, Augustin L S, Kendall C W. Nonalcoholic fatty liver, nonalcoholic steatohepatitis, ectopic fat, and the glycemic index.  Am J Clin Nutr. 2006;  84(1) 3-4
• 128 Solga S, Alkhuraishe A R, Clark J M et al.. Dietary composition and nonalcoholic fatty liver disease.  Dig Dis Sci. 2004;  49(10) 1578-1583
• 129 Toshimitsu K, Matsuura B, Ohkubo I et al.. Dietary habits and nutrient intake in non-alcoholic steatohepatitis.  Nutrition. 2007;  23(1) 46-52
• 130 Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R et al.. Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): a population based study.  J Hepatol. 2007;  47(5) 711-717
• 131 Solga S F, Diehl A M. Non-alcoholic fatty liver disease: lumen-liver interactions and possible role for probiotics.  J Hepatol. 2003;  38(5) 681-687
• 132 Solga S F, Diehl A M. Gut flora-based therapy in liver disease? The liver cares about the gut.  Hepatology. 2004;  39(5) 1197-1200
• 133 Wigg A J, Roberts-Thomson I C, Dymock R B, McCarthy P J, Grose R H, Cummins A G. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis.  Gut. 2001;  48(2) 206-211
• 134 Ekstedt M, Franzen L E, Mathiesen U L et al.. Long-term follow-up of patients with NAFLD and elevated liver enzymes.  Hepatology. 2006;  44(4) 865-873
• 135 Hashimoto E, Yatsuji S, Kaneda H et al.. The characteristics and natural history of Japanese patients with nonalcoholic fatty liver disease.  Hepatol Res. 2005;  33(2) 72-76
• 136 Hui J M, Kench J G, Chitturi S et al.. Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C.  Hepatology. 2003;  38(2) 420-427
• 137 Sanyal A J, Banas C, Sargeant C et al.. Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C.  Hepatology. 2006;  43(4) 682-689
• 138 Sanyal A J. AGA technical review on nonalcoholic fatty liver disease.  Gastroenterology. 2002;  123(5) 1705-1725
• 139 Villanova N, Moscatiello S, Ramilli S et al.. Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease.  Hepatology. 2005;  42(2) 473-480
• 140 Volzke H, Robinson D M, Kleine V et al.. Hepatic steatosis is associated with an increased risk of carotid atherosclerosis.  World J Gastroenterol. 2005;  11(12) 1848-1853
• 141 Stranges S, Trevisan M, Dorn J M, Dmochowski J, Donahue R P. Body fat distribution, liver enzymes, and risk of hypertension: evidence from the Western New York Study.  Hypertension. 2005;  46(5) 1186-1193
• 142 Hanley A J, Williams K, Festa A et al.. Elevations in markers of liver injury and risk of type 2 diabetes: the insulin resistance atherosclerosis study.  Diabetes. 2004;  53(10) 2623-2632
• 143 Hanley A J, Williams K, Festa A, Wagenknecht L E, D'Agostino Jr R B, Haffner S M. Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study.  Diabetes. 2005;  54(11) 3140-3147