Nonalcoholic fatty liver disease: from clinical recognition to treatment

References

• Angulo P. Nonalcoholic fatty liver disease. N. Engl. J. Med.346(16), 1221–1231 (2002).
   PubMed Web of Science ®Google Scholar
• Caldwell SH, Crespo DM. The spectrum expanded: cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease. J. Hepatol.40(4), 578–584 (2004).
   PubMed Web of Science ®Google Scholar
• Sanyal AJ. AGA technical review on nonalcoholic fatty liver disease. Gastroenterology123(5), 1705–1725 (2002).
   PubMedGoogle Scholar
• Zelman S. The liver in obesity. AMA Arch. Intern. Med.90(2), 141–156 (1952).
   PubMedGoogle Scholar
• Catlin R. Liver dysfunction after intestinal bypass. JAMA236(15), 1693–1694 (1976).
   PubMedGoogle Scholar
• McGill DB, Humpherys SR, Baggenstoss AH, Dickson ER. Cirrhosis and death after jejunoileal shunt. Gastroenterology63(5), 872–877 (1972).
   PubMed Web of Science ®Google Scholar
• Payne JH, Dewind LT, Commons RR. Metabolic observations in patients with jejunocolic shunts. Am. J. Surg.106, 273–289 (1963).
   PubMed Web of Science ®Google Scholar
• Adler M, Schaffner F. Fatty liver hepatitis and cirrhosis in obese patients. Am. J. Med.67(5), 811–816 (1979).
   PubMed Web of Science ®Google Scholar
• Nasrallah SM, Wills CE Jr, Galambos JT. Hepatic morphology in obesity. Dig. Dis. Sci.26(4), 325–327 (1981).
   PubMed Web of Science ®Google Scholar
• Thaler H. Relation of steatosis to cirrhosis. Clin. Gastroenterol.,4(2), 273–280 (1975).
   PubMedGoogle Scholar
• Falchuk KR, Fiske SC, Haggitt RC, Federman M, Trey C. Pericentral hepatic fibrosis and intracellular hyalin in diabetes mellitus. Gastroenterology78(3), 535–541 (1980).
   PubMedGoogle Scholar
• Itoh S, Tsukada Y, Motomura Y, Ichinoe A. Five patients with nonalcoholic diabetic cirrhosis. Acta Hepatogastroenterol. (Stuttg.)26(2), 90–97 (1979).
   PubMed Web of Science ®Google Scholar
• Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin. Proc.55(7), 434–438 (1980).
   PubMed Web of Science ®Google Scholar
• Cairns SR, Peters TJ. Biochemical analysis of hepatic lipid in alcoholic and diabetic and control subjects. Clin. Sci. (Lond.)65(6), 645–652 (1983).
   PubMedGoogle Scholar
• Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology37(5), 1202–1219 (2003).
   PubMed Web of Science ®Google Scholar
• Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am. J. Gastroenterol.98(5), 960–967 (2003).
   PubMed Web of Science ®Google Scholar
• 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.94(10), 3010–3014 (1999).
   PubMed Web of Science ®Google Scholar
• Tsochatzis E, Papatheodoridis GV, Manesis EK et al. Hepatic steatosis in genotype 4 chronic hepatitis C is mainly because of metabolic factors. Am. J. Gastroenterol.102(3), 634–641 (2007).
   PubMed Web of Science ®Google Scholar
• Skelly MM, James PD, Ryder SD. Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J. Hepatol.35(2), 195–199 (2001).
   PubMed Web of Science ®Google Scholar
• Mofrad P, Contos MJ, Haque M et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology37(6), 1286–1292 (2003).
   PubMed Web of Science ®Google Scholar
• Bacon BR, Farahvash MJ, Janney CG, Neuschwander-Tetri BA. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology107(4), 1103–1109 (1994).
   PubMed Web of Science ®Google Scholar
• Falck-Ytter Y, Younossi ZM, Marchesini G, McCullough AJ. Clinical features and natural history of nonalcoholic steatosis syndromes. Semin. Liver Dis.21(1), 17–26 (2001).
   PubMed Web of Science ®Google Scholar
• Younossi ZM, Diehl AM, Ong JP. Nonalcoholic fatty liver disease: an agenda for clinical research. Hepatology35(4), 746–752 (2002).
   PubMed Web of Science ®Google Scholar
• Szczepaniak LS, 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.288(2), E462–E468 (2005).
   PubMed Web of Science ®Google Scholar
• Saadeh S, Younossi ZM, Remer EM et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology123(3), 745–750 (2002).
   PubMed Web of Science ®Google Scholar
• Hilden M, Christoffersen P, Juhl E, Dalgaard JB. Liver histology in a ‘normal’ population – examinations of 503 consecutive fatal traffic casualties. Scand. J. Gastroenterol.12(5), 593–597 (1977).
   PubMed Web of Science ®Google Scholar
• Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology124(1), 71–79 (2003).
   PubMed Web of Science ®Google Scholar
• Bellentani S, Saccoccio G, Masutti F et al. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann. Intern. Med.132(2), 112–117 (2000).
   PubMed Web of Science ®Google Scholar
• Marcos A, Fisher RA, Ham JM et al. Selection and outcome of living donors for adult to adult right lobe transplantation. Transplantation69(11), 2410–2415 (2000).
   PubMed Web of Science ®Google Scholar
• Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. Hepatology12(5), 1106–1110 (1990).
   PubMed Web of Science ®Google Scholar
• Machado M, Marques-Vidal P, Cortez-Pinto H. Hepatic histology in obese patients undergoing bariatric surgery. J. Hepatol.45(4), 600–606 (2006).
   PubMed Web of Science ®Google Scholar
• Noguchi H, Tazawa Y, Nishinomiya F, Takada G. The relationship between serum transaminase activities and fatty liver in children with simple obesity. Acta Paediatr. Jpn.37(5), 621–625 (1995).
   PubMedGoogle Scholar
• Tominaga K, Kurata JH, Chen YK et al. Prevalence of fatty liver in Japanese children and relationship to obesity. An epidemiological ultrasonographic survey. Dig. Dis. Sci.40(9), 2002–2009 (1995).
   PubMed Web of Science ®Google Scholar
• Lobstein T, Baur L, Uauy R. Obesity in children and young people: a crisis in public health. Obes. Rev.5(Suppl. ), 4–104 (2004).
   PubMedGoogle Scholar
• Ogden CL, Carroll MD, Curtin LR et al. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA295(13), 1549–1555 (2006).
   PubMed Web of Science ®Google Scholar
• James PT, Rigby N, Leach R. The obesity epidemic, metabolic syndrome and future prevention strategies. Eur. J. Cardiovasc. Prev. Rehabil.11(1), 3–8 (2004).
   PubMed Web of Science ®Google Scholar
• Cecil JE, Watt P, Murrie IS et al. Childhood obesity and socioeconomic status: a novel role for height growth limitation. Int. J. Obes. (Lond.), 29–10), 1199–1203 (2005).
   PubMedGoogle Scholar
• Willms JD, Tremblay MS, Katzmarzyk PT. Geographic and demographic variation in the prevalence of overweight Canadian children. Obes. Res.11(5), 668–673 (2003).
   PubMedGoogle Scholar
• Magarey AM, Daniels LA, Boulton TJ. Prevalence of overweight and obesity in Australian children and adolescents: reassessment of 1985 and 1995 data against new standard international definitions. Med. J. Aust.,174(11) 561–564 (2001).
   PubMed Web of Science ®Google Scholar
• Rashid M, Roberts EA. Nonalcoholic steatohepatitis in children. J. Pediatr. Gastroenterol. Nutr.30(1), 48–53 (2000).
   PubMed Web of Science ®Google Scholar
• Franzese A, Vajro P, Argenziano A et al. Liver involvement in obese children. Ultrasonography and liver enzyme levels at diagnosis and during follow-up in an Italian population. Dig. Dis. Sci.42(7), 1428–1432 (1997).
   PubMed Web of Science ®Google Scholar
• Schwimmer JB, Deutsch R, Kahen T et al. Prevalence of fatty liver in children and adolescents. Pediatrics118(4), 1388–1393 (2006).
   PubMed Web of Science ®Google Scholar
• Teli MR, James OF, Burt AD, Bennett MK, Day CP. The natural history of nonalcoholic fatty liver: a follow-up study. Hepatology22(6), 1714–1719 (1995).
   PubMed Web of Science ®Google Scholar
• Powell EE, Cooksley WG, Hanson R et al. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology11(1), 74–80 (1990).
   PubMed Web of Science ®Google Scholar
• Lee RG. Nonalcoholic steatohepatitis: a study of 49 patients. Hum. Pathol.20(6), 594–598 (1989).
   PubMed Web of Science ®Google Scholar
• Diehl AM, Goodman Z, Ishak KG. Alcohollike liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury. Gastroenterology95(4), 1056–1062 (1988).
   Google Scholar
• Matteoni CA, Younossi ZM, Gramlich T et al. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology116(6), 1413–1419 (1999).
   PubMed Web of Science ®Google Scholar
• 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.65(777), 774–778 (1992).
   PubMedGoogle Scholar
• Nomura H, Kashiwagi S, Hayashi J et al. Prevalence of fatty liver in a general population of Okinawa, Japan. Jpn. J. Med.27(2), 142–149 (1988).
   PubMedGoogle Scholar
• Nonomura A, Mizukami Y, Unoura M et al. Clinicopathologic study of alcohol-like liver disease in non-alcoholics; non-alcoholic steatohepatitis and fibrosis. Gastroenterol. Jpn.27(4), 521–528 (1992).
   PubMedGoogle Scholar
• Omagari K, Kadokawa Y, Masuda J et al. Fatty liver in non-alcoholic non-overweight Japanese adults: incidence and clinical characteristics. J. Gastroenterol. Hepatol.17(10), 1098–1105 (2002).
   PubMed Web of Science ®Google Scholar
• Lonardo A, Bellini M, Tartoni P, Tondelli E. The bright liver syndrome. Prevalence and determinants of a “bright” liver echopattern. Ital. J. Gastroenterol. Hepatol.29(4), 351–356 (1997).
   PubMed Web of Science ®Google Scholar
• Kemmer N, McKinney K, Vuaim SY et al. High prevalence of NASH among Mexican American females with Type II diabetes melitus. Gastroenterology120, 117A (2001).
   PubMedGoogle Scholar
• Browning JD, Szczepaniak LS, Dobbins R et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology40(6), 1387–1395 (2004).
   PubMed Web of Science ®Google Scholar
• Weston SR, Leyden W, Murphy R et al. Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease. Hepatology41(2), 372–379 (2005).
   PubMed Web of Science ®Google Scholar
• Silverman JF, O’Brien KF, Long S et al. Liver pathology in morbidly obese patients with and without diabetes. Am. J. Gastroenterol.85(10), 1349–1355 (1990).
   PubMed Web of Science ®Google Scholar
• Dixon JB, Bhathal PS, O’Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology121(1), 91–100 (2001).
   PubMed Web of Science ®Google Scholar
• Eriksson S, Eriksson KF, Bondesson L. Nonalcoholic steatohepatitis in obesity: a reversible condition. Acta Med. Scand.220(1), 83–88 (1986).
   PubMed Web of Science ®Google Scholar
• Luyckx FH, Desaive C, Thiry A et al. Liver abnormalities in severely obese subjects: effect of drastic weight loss after gastroplasty. Int. J. Obes. Relat. Metab. Disord.22(3), 222–226 (1998).
   PubMed Web of Science ®Google Scholar
• Park HS, Kim MW, Shin ES. Effect of weight control on hepatic abnormalities in obese patients with fatty liver. J. Korean Med. Sci.10(6), 414–421 (1995).
   PubMedGoogle Scholar
• Ranlov I, Hardt F. Regression of liver steatosis following gastroplasty or gastric bypass for morbid obesity. Digestion47(4), 208–214 (1990).
   PubMed Web of Science ®Google Scholar
• Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL. Overweight and obesity in the United States: prevalence and trends, 1960–1994. Int. J. Obes. Relat. Metab. Disord.22(1), 39–47 (1998).
   PubMed Web of Science ®Google Scholar
• Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology30(6), 1356–1362 (1999).
   PubMed Web of Science ®Google Scholar
• Mendler MH, Turlin B, Moirand R et al. Insulin resistance-associated hepatic iron overload. Gastroenterology117(5), 1155–1163 (1999).
   PubMed Web of Science ®Google Scholar
• Gillum RF, Mussolino ME, Madans JH. Body fat distribution and hypertension incidence in women and men. The NHANES I Epidemiologic Follow-up Study. Int. J. Obes. Relat. Metab. Disord.22(2), 127–134 (1998).
   PubMed Web of Science ®Google Scholar
• Kral JG, Schaffner F, Pierson RN Jr, Wang J. Body fat topography as an independent predictor of fatty liver. Metabolism42(5), 548–551 (1993).
   PubMed Web of Science ®Google Scholar
• Targher G, Bertolini L, Padovani R et al. Relation of nonalcoholic hepatic steatosis to early carotid atherosclerosis in healthy men: role of visceral fat accumulation. Diabetes Care27(10), 2498–2500 (2004).
   PubMedGoogle Scholar
• Villanova N, Moscatiello S, Ramilli S et al. Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. Hepatology42(2), 473–480 (2005).
   PubMed Web of Science ®Google Scholar
• Volzke H, Robinson DM, Kleine V et al. Hepatic steatosis is associated with an increased risk of carotid atherosclerosis. World J. Gastroenterol.11(12), 1848–1853 (2005).
   PubMedGoogle Scholar
• Akahoshi M, Amasaki Y, Soda M et al. Correlation between fatty liver and coronary risk factors: a population study of elderly men and women in Nagasaki, Japan. Hypertens. Res.24(4), 337–343 (2001).
   PubMedGoogle Scholar
• Hornboll P, Olsen TS. Fatty changes in the liver: the relation to age, overweight and diabetes mellitus. Acta Pathol. Microbiol. Immunol. Scand. (A)90(3), 199–205 (1982).
   PubMedGoogle Scholar
• Hsieh SD, Yoshinaga H, Muto T, Sakurai Y. Regular physical activity and coronary risk factors in Japanese men. Circulation97(7), 661–665 (1998).
   PubMed Web of Science ®Google Scholar
• Ikai E, Honda R, Yamada Y. Serum gamma-glutamyl transpeptidase level and blood pressure in nondrinkers: a possible pathogenetic role of fatty liver in obesity-related hypertension. J. Hum. Hypertens.8(2), 95–100 (1994).
   PubMed Web of Science ®Google Scholar
• Ikai E, Ishizaki M, Suzuki Y et al. Association between hepatic steatosis, insulin resistance and hyperinsulinaemia as related to hypertension in alcohol consumers and obese people. J. Hum. Hypertens.9(2), 101–105 (1995).
   PubMed Web of Science ®Google Scholar
• Lonardo A. Fatty liver and nonalcoholic steatohepatitis. Where do we stand and where are we going? Dig .Dis.17(2), 80–89 (1999).
   PubMed Web of Science ®Google Scholar
• Marchesini G, Brizi M, Morselli-Labate AM et al. Association of nonalcoholic fatty liver disease with insulin resistance. Am. J. Med.107(5), 450–455 (1999).
   PubMed Web of Science ®Google Scholar
• Maruhama Y, Abe R, Okuguchi F et al. Interactions of obesity and glucose-stimulated insulin secretion in familial hypertriglyceridemia. Diabetes27(6), 682–693 (1978).
   PubMedGoogle Scholar
• Bonkovsky HL, Jawaid Q, Tortorelli K et al. Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis. J. Hepatol.31(3), 421–429 (1999).
   PubMedGoogle Scholar
• Clouston AD, Powell EE. Interaction of non-alcoholic fatty liver disease with other liver diseases. Best Pract. Res. Clin. Gastroenterol.16(5), 767–781 (2002).
   PubMedGoogle Scholar
• Asselah T, Rubbia-Brandt L, Marcellin P, Negro F. Steatosis in chronic hepatitis C: why does it really matter?Gut55(1), 123–130 (2006).
   PubMed Web of Science ®Google Scholar
• Rubbia-Brandt L, Quadri R, Abid K et al. Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3. J. Hepatol.33(1), 106–115 (2000).
   PubMed Web of Science ®Google Scholar
• Moriya K, Yotsuyanagi H, Shintani Y et al. Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. J. Gen. Virol.78 (Pt 7), 1527–1531 (1997).
   PubMed Web of Science ®Google Scholar
• Perlemuter G, Sabile A, Letteron P et al. Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis. FASEB J.16(2), 185–194 (2002).
   PubMed Web of Science ®Google Scholar
• Hourigan LF, Macdonald GA, Purdie D et al. Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. Hepatology29(4), 1215–1219 (1999).
   PubMed Web of Science ®Google Scholar
• Adinolfi LE, Gambardella M, Andreana A et al. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology33(6), 1358–1364 (2001).
   PubMed Web of Science ®Google Scholar
• Westin J, Nordlinder H, Lagging M, Norkrans G, Wejstal R. Steatosis accelerates fibrosis development over time in hepatitis C virus genotype 3 infected patients. J. Hepatol.37(6), 837–842 (2002).
   PubMed Web of Science ®Google Scholar
• Manton ND, Lipsett J, Moore DJ et al. Non-alcoholic steatohepatitis in children and adolescents. Med. J. Aust.173(9), 476–479 (2000).
   PubMed Web of Science ®Google Scholar
• Itoh S, Yougel T, Kawagoe K. Comparison between nonalcoholic steatohepatitis and alcoholic hepatitis. Am. J. Gastroenterol.82(7), 650–654 (1987).
   PubMedGoogle Scholar
• Pantsari MW, Harrison SA. Nonalcoholic fatty liver disease presenting with an isolated elevated alkaline phosphatase. J. Clin. Gastroenterol.40(7), 633–635 (2006).
   PubMed Web of Science ®Google Scholar
• Pinto HC, Baptista A, Camilo ME et al. Nonalcoholic steatohepatitis. Clinicopathological comparison with alcoholic hepatitis in ambulatory and hospitalized patients. Dig. Dis. Sci.41(1), 172–179 (1996).
   PubMed Web of Science ®Google Scholar
• Tajiri K, Takenawa H, Yamaoka K et al. Nonalcoholic steatohepatitis masquerading as autoimmune hepatitis. J. Clin. Gastroenterol.25(3), 538–540 (1997).
   PubMedGoogle Scholar
• George DK, Goldwurm S, Macdonald GA et al. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology114(2), 311–318 (1998).
   PubMed Web of Science ®Google Scholar
• Ratziu V, Giral P, Charlotte F et al. Liver fibrosis in overweight patients. Gastroenterology118(6), 1117–1123 (2000).
   PubMed Web of Science ®Google Scholar
• Younossi ZM, Gramlich T, Bacon BR et al. Hepatic iron and nonalcoholic fatty liver disease. Hepatology30(4), 847–850 (1999).
   PubMedGoogle Scholar
• Assy N, Schlesinger S, Hussein O. Elevated plasma protein C levels correlate with the presence of fatty liver (NASH and NAFLD). Gut54(5), 729 (2005).
   PubMedGoogle Scholar
• Chitturi S, Abeygunasekera S, Farrell GC et al. NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology35(2), 373–379 (2002).
   PubMed Web of Science ®Google Scholar
• Fishbein M, Castro F, Cheruku S et al. Hepatic MRI for fat quantitation: its relationship to fat morphology, diagnosis, and ultrasound. J. Clin. Gastroenterol.39(7), 619–625 (2005).
   PubMed Web of Science ®Google Scholar
• Mottin CC, Moretto M, Padoin AV et al. The role of ultrasound in the diagnosis of hepatic steatosis in morbidly obese patients. Obes. Surg.14(5), 635–637 (2004).
   PubMed Web of Science ®Google Scholar
• Mitchell DG. Focal manifestations of diffuse liver disease at MR imaging. Radiology185(1), 1–11 (1992).
   PubMed Web of Science ®Google Scholar
• Debaere C, Rigauts H, Laukens P. Transient focal fatty liver infiltration mimicking liver metastasis. J. Belge Radiol., 81(4), 174–175 (1998).
   PubMedGoogle Scholar
• Sheth SG, Gordon FD, Chopra S. Nonalcoholic steatohepatitis [see comments] [published erratum appears in Ann.Intern. Med. 1997 Oct 15; 127(8 Pt 1):658]. Ann. Intern. Med.126(2), 137–145 (1997).
   PubMed Web of Science ®Google Scholar
• Van Ness MM, Diehl AM. Is liver biopsy useful in the evaluation of patients with chronically elevated liver enzymes? Ann. Intern. Med.111(6), 473–478 (1989).
   Google Scholar
• Sorbi D, McGill DB, Thistle JL et al. An assessment of the role of liver biopsies in asymptomatic patients with chronic liver test abnormalities. Am. J. Gastroenterol.95(11), 3206–3210 (2000).
   PubMed Web of Science ®Google Scholar
• Baldridge AD, Perez-Atayde AR, Graeme-Cook F, Higgins L, Lavine JE. Idiopathic steatohepatitis in childhood: a multicenter retrospective study. J. Pediatr.127(5), 700–704 (1995).
   PubMed Web of Science ®Google Scholar
• Imbert-Bismut F, Ratziu V, Pieroni L et al. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet357(9262), 1069–1075 (2001).
   PubMed Web of Science ®Google Scholar
• Wai CT, Greenson JK, Fontana RJ et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology38(2), 518–526 (2003).
   PubMed Web of Science ®Google Scholar
• Ziol M, Handra-Luca A, Kettaneh A et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology41(1), 48–54 (2005).
   PubMed Web of Science ®Google Scholar
• Gomez-Dominguez E, Mendoza J, Rubio S et al. Transient elastography: a valid alternative to biopsy in patients with chronic liver disease. Aliment Pharmacol. Ther.24(3), 513–518 (2006).
   PubMed Web of Science ®Google Scholar
• Foucher J, Chanteloup E, Vergniol J et al. Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut55(3), 403–408 (2006).
   PubMed Web of Science ®Google Scholar
• Castera L, Vergniol J, Foucher J et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology128(2), 343–350 (2005).
   PubMed Web of Science ®Google Scholar
• Duarte IF, Stanley EG, Holmes E et al. Metabolic assessment of human liver transplants from biopsy samples at the donor and recipient stages using high-resolution magic angle spinning 1H NMR spectroscopy. Anal. Chem.77(17), 5570–5578 (2005).
   PubMed Web of Science ®Google Scholar
• Chitturi S, Farrell GC. Etiopathogenesis of nonalcoholic steatohepatitis. Semin. Liver Dis.21(1), 27–41 (2001).
   PubMed Web of Science ®Google Scholar
• Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N. Engl. J. Med.343(20), 1467–1476 (2000).
   PubMed Web of Science ®Google Scholar
• Pagano G, Pacini G, Musso G et al. Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association. Hepatology35(2), 367–372 (2002).
   PubMed Web of Science ®Google Scholar
• Marchesini G, Bugianesi E, Forlani G et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology37(4), 917–923 (2003).
   PubMed Web of Science ®Google Scholar
• Day CP, James OF. Steatohepatitis: a tale of two “hits”. Gastroenterology114(4), 842–845 (1998).
   PubMed Web of Science ®Google Scholar
• Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic. Biol. Med.11(1), 81–128 (1991).
   PubMed Web of Science ®Google Scholar
• Osmundsen H, Bremer J, Pedersen JI. Metabolic aspects of peroxisomal β-oxidation. Biochim. Biophys. Acta1085(2), 141–158 (1991).
   PubMed Web of Science ®Google Scholar
• Hug H, Strand S, Grambihler A et al. Reactive oxygen intermediates are involved in the induction of CD95 ligand mRNA expression by cytostatic drugs in hepatoma cells. J. Biol. Chem.272(45), 28191–28193 (1997).
   PubMed Web of Science ®Google Scholar
• Feldstein AE, Canbay A, Angulo P et al. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology125(2), 437–443 (2003).
   PubMed Web of Science ®Google Scholar
• Reaven GM. Banting Lecture 1988. Role of insulin resistance in human disease. 1988. Nutrition13(1), 65 (1997).
   PubMedGoogle Scholar
• Khalili K, Lan FP, Hanbidge AE et al. Hepatic subcapsular steatosis in response to intraperitoneal insulin delivery: CT findings and prevalence. AJR Am. J. Roentgenol.180(6), 1601–1604 (2003).
   PubMed Web of Science ®Google Scholar
• Sanyal AJ, Campbell-Sargent C, Mirshahi F et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology120(5), 1183–1192 (2001).
   PubMed Web of Science ®Google Scholar
• Charlton M, Sreekumar R, Rasmussen D, Lindor K, Nair KS. Apolipoprotein synthesis in nonalcoholic steatohepatitis. Hepatology35(4), 898–904 (2002).
   PubMed Web of Science ®Google Scholar
• Kim JK, Fillmore JJ, Chen Y et al. Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc. Natl Acad. Sci. USA98(13), 7522–7527 (2001).
   PubMed Web of Science ®Google Scholar
• Magnusson I, Rothman DL, Katz LD, Shulman RG, Shulman GI. Increased rate of gluconeogenesis in type II diabetes mellitus. A13 C nuclear magnetic resonance study. J. Clin. Invest.90(4), 1323–1327 (1992).
   PubMed Web of Science ®Google Scholar
• Rothman DL, Magnusson I, Katz LD, Shulman RG, Shulman GI. Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13C NMR. Science254(5031), 573–576 (1991).
   PubMed Web of Science ®Google Scholar
• Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance. J. Clin. Invest.95(5), 2409–2415 (1995).
   PubMed Web of Science ®Google Scholar
• Tsochatzis E, Papatheodoridis GV, Archimandritis AJ. The evolving role of leptin and adiponectin in chronic liver diseases. Am. J. Gastroenterol.101(11), 2629–2640 (2006).
   PubMed Web of Science ®Google Scholar
• Anania FA. Leptin, liver, and obese mice – fibrosis in the fat lane. Hepatology36(1), 246–248 (2002).
   PubMed Web of Science ®Google Scholar
• Ikejima K, Takei Y, Honda H et al. Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat. Gastroenterology122(5), 1399–1410 (2002).
   PubMed Web of Science ®Google Scholar
• Kaplan LM. Leptin, obesity, and liver disease. Gastroenterology115(4), 997–1001 (1998).
   PubMed Web of Science ®Google Scholar
• Saxena NK, Ikeda K, Rockey DC, Friedman SL, Anania FA. Leptin in hepatic fibrosis: evidence for increased collagen production in stellate cells and lean littermates of ob/ob mice. Hepatology35(4), 762–771 (2002).
   PubMed Web of Science ®Google Scholar
• Nosadini R, Avogaro A, Mollo F et al. Carbohydrate and lipid metabolism in cirrhosis. Evidence that hepatic uptake of gluconeogenic precursors and of free fatty acids depends on effective hepatic flow. J. Clin. Endocrinol. Metab.58(6), 1125–1132 (1984).
   PubMedGoogle Scholar
• Caldwell SH, Swerdlow RH, Khan EM et al. Mitochondrial abnormalities in non-alcoholic steatohepatitis. J. Hepatol.31(3), 430–434 (1999).
   PubMed Web of Science ®Google Scholar
• Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology132(6), 2169–2180 (2007).
   PubMed Web of Science ®Google Scholar
• Weisberg SP, Hunter D, Huber R et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J. Clin. Invest116(1), 115–124 (2006).
   PubMed Web of Science ®Google Scholar
• Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J. Clin. Endocrinol. Metab.83(3), 847–850 (1998).
   PubMed Web of Science ®Google Scholar
• Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology145(5), 2273–2282 (2004).
   PubMed Web of Science ®Google Scholar
• Cai D, Yuan M, Frantz DF et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nat Med, 11(2), 183–190 (2005).
   PubMed Web of Science ®Google Scholar
• Shi H, Kokoeva MV, Inouye K et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest116(11), 3015–3025 (2006).
   PubMed Web of Science ®Google Scholar
• Lee JY, Sohn KH, Rhee SH, Hwang D. Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J. Biol. Chem.276(20), 16683–16689 (2001).
   PubMed Web of Science ®Google Scholar
• Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology122(6), 1649–1657 (2002).
   PubMed Web of Science ®Google Scholar
• Marceau P, Biron S, Hould FS et al. Liver pathology and the metabolic syndrome X in severe obesity. J. Clin. Endocrinol. Metab.84(5), 1513–1517 (1999).
   PubMed Web of Science ®Google Scholar
• Andersen T, Gluud C, Franzmann MB, Christoffersen P. Hepatic effects of dietary weight loss in morbidly obese subjects. J. Hepatol.12(2), 224–229 (1991).
   PubMed Web of Science ®Google Scholar
• Adams LA, Lymp JF, St Sauver J et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology129(1), 113–121 (2005).
   PubMed Web of Science ®Google Scholar
• Dam-Larsen S, Franzmann M, Andersen IB et al. Long term prognosis of fatty liver: risk of chronic liver disease and death. Gut53(5), 750–755 (2004).
   PubMed Web of Science ®Google Scholar
• Harrison SA, Torgerson S, Hayashi PH. The natural history of nonalcoholic fatty liver disease: a clinical histopathological study. Am. J. Gastroenterol.98(9), 2042–2047 (2003).
   PubMed Web of Science ®Google Scholar
• Bellentani S, Bedogni G, Miglioli L et al. Natural history and incidence of non alcoholic and alcoholic fatty liver disease (NAFLD, AFLD) in the general population with alteration of liver enzymes. J. Hepatol.42(Suppl. 2), 3 (2005).
   PubMedGoogle Scholar
• Ekstedt M, Franzen LE, Mathiesen UL et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology44(4), 865–873 (2006).
   PubMed Web of Science ®Google Scholar
• Adams LA, Sanderson S, Lindor KD, Angulo P. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J. Hepatol.42(1), 132–138 (2005).
   PubMed Web of Science ®Google Scholar
• Fassio E, Alvarez E, Dominguez N, Landeira G, Longo C. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology40(4), 820–826 (2004).
   PubMed Web of Science ®Google Scholar
• Caldwell SH, Oelsner DH, Iezzoni JC et al. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology29(3), 664–669 (1999).
   PubMed Web of Science ®Google Scholar
• Poonawala A, Nair SP, Thuluvath PJ. Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: a case–control study. Hepatology32(4 Pt 1), 689–692 (2000).
   PubMed Web of Science ®Google Scholar
• Powell EE, Jonsson JR, Clouston AD. Dangerous liaisons: the metabolic syndrome and nonalcoholic fatty liver disease. Ann. Intern. Med.143(10), 753–754 (2005).
   PubMedGoogle Scholar
• Ioannou GN, Weiss NS, Kowdley KV, Dominitz JA. Is obesity a risk factor for cirrhosis-related death or hospitalization? A population-based cohort study. Gastroenterology125(4), 1053–1059 (2003).
   PubMed Web of Science ®Google Scholar
• El Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology126(2), 460–468 (2004).
   PubMedGoogle Scholar
• Hui JM, Kench JG, Chitturi S et al. Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C. Hepatology38(2), 420–427 (2003).
   PubMed Web of Science ®Google Scholar
• Ratziu V, Bonyhay L, Di MV et al. Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis. Hepatology35(6), 1485–1493 (2002).
   PubMed Web of Science ®Google Scholar
• Bugianesi E, Leone N, Vanni E et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology123(1), 134–140 (2002).
   PubMed Web of Science ®Google Scholar
• Bugianesi E. Review article: steatosis, the metabolic syndrome and cancer. Aliment. Pharmacol. Ther.22(Suppl. 2), 40–43 (2005).
   PubMedGoogle Scholar
• Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med.348(17), 1625–1638 (2003).
   PubMed Web of Science ®Google Scholar
• Murphy TK, Calle EE, Rodriguez C, Kahn HS, Thun MJ. Body mass index and colon cancer mortality in a large prospective study. Am. J. Epidemiol.,152(9), 847–854 (2000).
   PubMed Web of Science ®Google Scholar
• Marrero JA, Fontana RJ, Su GL et al. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology36(6), 1349–1354 (2002).
   PubMed Web of Science ®Google Scholar
• Ueno T, Sugawara H, Sujaku K et al. Therapeutic effects of restricted diet and exercise in obese patients with fatty liver. J. Hepatol.27(1), 103–107 (1997).
   PubMed Web of Science ®Google Scholar
• Vajro P, Fontanella A, Perna C et al. Persistent hyperaminotransferasemia resolving after weight reduction in obese children. J. Pediatr.125(2), 239–241 (1994).
   PubMedGoogle Scholar
• Dean RH, Scott HW Jr, Shull HJ, Gluck FW. Morbid obesity: problems associated with operative management. Am. J. Clin. Nutr.30(1), 90–97 (1977).
   PubMedGoogle Scholar
• Drenick EJ, Simmons F, Murphy JF. Effect on hepatic morphology of treatment of obesity by fasting, reducing diets and small-bowel bypass. N. Engl. J. Med.282(15), 829–834 (1970).
   PubMed Web of Science ®Google Scholar
• Marchesini G, Suppini A, Forlani G. NAFLD treatment: cognitive-behavioral therapy has entered the arena. J. Hepatol.43(6), 926–928 (2005).
   PubMedGoogle Scholar
• Rollins G. Moderate exercise reduces the risk of heart disease and death in men with type 2 diabetes. Rep. Med. Guidel. Outcomes. Res.14(11), 10–12 (2003).
   Google Scholar
• Eden KB, Orleans CT, Mulrow CD, Pender NJ, Teutsch SM. Does counseling by clinicians improve physical activity? A summary of the evidence for the U.S. Preventive Services Task Force. Ann. Intern. Med.137(3), 208–215 (2002).
   Google Scholar
• Hoppeler H. Skeletal muscle substrate metabolism. Int. J. Obes. Relat. Metab. Disord.23(Suppl. 3), S7–S10 (1999).
   PubMedGoogle Scholar
• Jones NL, Killian KJ. Exercise limitation in health and disease. N. Engl. J. Med.343(9), 632–641 (2000).
   Google Scholar
• Tuomilehto J, Lindstrom J, Eriksson JG et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N. Engl. J. Med.344(18), 1343–1350 (2001).
   PubMed Web of Science ®Google Scholar
• van Baak MA. Exercise training and substrate utilisation in obesity. Int. J. Obes. Relat. Metab. Disord.23(Suppl. 3) S11–S17 (1999).
   Google Scholar
• Hussein O, Grosovski M, Lasri E et al. Monounsaturated fat decreases hepatic lipid content in non-alcoholic fatty liver disease in rats. World J Gastroenterol, 13(3), 361–368 (2007).
   PubMed Web of Science ®Google Scholar
• Dhingra R, Sullivan L, Jacques PF et al. Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community. Circulation116(5), 480–488 (2007).
   PubMed Web of Science ®Google Scholar
• 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.47(5), 711–717 (2007).
   PubMed Web of Science ®Google Scholar
• Siebler J, Galle PR. Treatment of nonalcoholic fatty liver disease. World J. Gastroenterol.12(14), 2161–2167 (2006).
   PubMed Web of Science ®Google Scholar
• Kraus WE, Houmard JA, Duscha BD et al. Effects of the amount and intensity of exercise on plasma lipoproteins. N. Engl. J. Med.347(19), 1483–1492 (2002).
   PubMed Web of Science ®Google Scholar
• Angulo P, Lindor KD. Treatment of nonalcoholic fatty liver: present and emerging therapies. Semin. Liver Dis.21(1), 81–88 (2001).
   PubMed Web of Science ®Google Scholar
• Suzuki A, Lindor K, St SJ et al. Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J. Hepatol.43(6), 1060–1066 (2005).
   PubMed Web of Science ®Google Scholar
• Huang MA, Greenson JK, Chao C et al. One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study. Am. J. Gastroenterol.100(5), 1072–1081 (2005).
   PubMed Web of Science ®Google Scholar
• Ryan DH. Use of sibutramine to treat obesity. Prim. Care30(2), 405–426 (2003).
   PubMed Web of Science ®Google Scholar
• Harrison SA, Fincke C, Helinski D, Torgerson S, Hayashi P. A pilot study of orlistat treatment in obese, non-alcoholic steatohepatitis patients. Aliment. Pharmacol. Ther.20(6), 623–628 (2004).
   PubMed Web of Science ®Google Scholar
• Harrison SA, Ramrakhiani S, Brunt EM et al. Orlistat in the treatment of NASH: a case series. Am. J. Gastroenterol.98(4), 926–930 (2003).
   PubMed Web of Science ®Google Scholar
• Sabuncu T, Nazligul Y, Karaoglanoglu M, Ucar E, Kilic FB. The effects of sibutramine and orlistat on the ultrasonographic findings, insulin resistance and liver enzyme levels in obese patients with non-alcoholic steatohepatitis. Rom. J. Gastroenterol.12(3), 189–192 (2003).
   PubMedGoogle Scholar
• Zelber-Sagi S, Kessler A, Brazowsky E et al. A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol.4(5), 639–644 (2006).
   PubMed Web of Science ®Google Scholar
• Assy N, Hussein O, Abassi Z. Weight loss induced by orlistat reverses fatty infiltration and improves hepatic fibrosis in obese patients with non-alcoholic steatohepatitis. Gut56(3), 443–444 (2007).
   PubMed Web of Science ®Google Scholar
• Despres JP, Golay A, Sjostrom L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N. Engl. J. Med.353(20), 2121–2134 (2005).
   PubMed Web of Science ®Google Scholar
• Luyckx FH, Scheen AJ, Desaive C, Thiry A, Lefebvre PJ. Parallel reversibility of biological markers of the metabolic syndrome and liver steatosis after gastroplasty-induced weight loss in severe obesity. J. Clin. Endocrinol. Metab.84(11), 4293 (1999).
   PubMed Web of Science ®Google Scholar
• Laurin J, Lindor KD, Crippin JS et al. Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: a pilot study. Hepatology23(6), 1464–1467 (1996).
   PubMed Web of Science ®Google Scholar
• Basaranoglu M, Acbay O, Sonsuz A. A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis. J. Hepatol.31(2), 384 (1999).
   PubMed Web of Science ®Google Scholar
• Chalasani N, Aljadhey H, Kesterson J, Murray MD, Hall SD. Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroenterology126(5), 1287–1292 (2004).
   PubMed Web of Science ®Google Scholar
• Angulo P. Use of ursodeoxycholic acid in patients with liver disease. Curr. Gastroenterol. Rep.4(1), 37–44 (2002).
   PubMedGoogle Scholar
• Lindor KD, Kowdley KV, Heathcote EJ et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology39(3), 770–778 (2004).
   PubMed Web of Science ®Google Scholar
• Hasegawa T, Yoneda M, Nakamura K, Makino I, Terano A. Plasma transforming growth factor-β1 level and efficacy of α-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Aliment. Pharmacol. Ther.15(10), 1667–1672 (2001).
   PubMed Web of Science ®Google Scholar
• Lavine JE. Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study. J. Pediatr.136(6), 734–738 (2000).
   PubMed Web of Science ®Google Scholar
• Harrison SA, Torgerson S, Hayashi P, Ward J, Schenker S. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am. J. Gastroenterol.98(11), 2485–2490 (2003).
   PubMed Web of Science ®Google Scholar
• Abdelmalek MF, Angulo P, Jorgensen RA, Sylvestre PB, Lindor KD. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am. J. Gastroenterol.96(9), 2711–2717 (2001).
   PubMed Web of Science ®Google Scholar
• Marchesini G, Brizi M, Bianchi G et al. Metformin in non-alcoholic steatohepatitis. Lancet358(9285), 893–894 (2001).
   PubMed Web of Science ®Google Scholar
• Nair S, Diehl AM, Wiseman M, Farr GH Jr, Perrillo RP. Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment. Pharmacol. Ther.,20(1), 23–28 (2004).
   PubMed Web of Science ®Google Scholar
• Bugianesi E, Gentilcore E, Manini R et al. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am. J. Gastroenterol.100(5), 1082–1090 (2005).
   PubMed Web of Science ®Google Scholar
• Uygun A, Kadayifci A, Isik AT et al. Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment.Pharmacol.Ther.19(5), 537–544 (2004).
   PubMed Web of Science ®Google Scholar
• Aubert J, Champigny O, Saint-Marc P et al. Up-regulation of UCP-2 gene expression by PPAR agonists in preadipose and adipose cells. Biochem. Biophys. Res. Commun.238(2), 606–611 (1997).
   PubMedGoogle Scholar
• Kelly IE, Han TS, Walsh K, Lean ME. Effects of a thiazolidinedione compound on body fat and fat distribution of patients with type 2 diabetes. Diabetes Care, 22–2), 288–293 (1999).
   PubMed Web of Science ®Google Scholar
• Lenhard JM, Kliewer SA, Paulik MA et al. Effects of troglitazone and metformin on glucose and lipid metabolism: alterations of two distinct molecular pathways. Biochem. Pharmacol.54(7), 801–808 (1997).
   PubMed Web of Science ®Google Scholar
• Ribon V, Johnson JH, Camp HS, Saltiel AR. Thiazolidinediones and insulin resistance: peroxisome proliferatoractivated receptor γ activation stimulates expression of the CAP gene. Proc. Natl Acad. Sci. USA95(25), 14751–14756 (1998).
   PubMed Web of Science ®Google Scholar
• Vamecq J, Latruffe N. Medical significance of peroxisome proliferator-activated receptors. Lancet354(9173), 141–148 (1999).
   PubMed Web of Science ®Google Scholar
• Caldwell SH, Hespenheide EE, Redick JA et al. A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis. Am. J. Gastroenterol.96(2), 519–525 (2001).
   PubMed Web of Science ®Google Scholar
• Menon KVN, Angulo P, Lindor KD. Severe cholestatic hepatitis from troglitazone in a patient with nonalcoholic steatohepatitis and diabetes mellitus. Am. J. Gastroenterol.96(5), 1631–1634 (2001).
   PubMed Web of Science ®Google Scholar
• Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology38(4), 1008–1017 (2003).
   PubMed Web of Science ®Google Scholar
• Promrat K, Lutchman G, Uwaifo GI et al. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology39(1), 188–196 (2004).
   PubMed Web of Science ®Google Scholar
• Sanyal AJ, Mofrad PS, Contos MJ et al. A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Clin. Gastroenterol. Hepatol.2(12), 1107–1115 (2004).
   PubMed Web of Science ®Google Scholar
• Belfort R, Harrison SA, Brown K et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N. Engl. J. Med.355(22), 2297–2307 (2006).
   PubMed Web of Science ®Google Scholar
• Marchesini G, Natale S, Manini R, Agostini F. Review article: the treatment of fatty liver disease associated with the metabolic syndrome. Aliment. Pharmacol. Ther.22(Suppl. 2), 37–39 (2005).
   PubMedGoogle Scholar
• Garcia-Ruiz I, Rodriguez-Juan C, Diaz-Sanjuan T et al. Effects of rosiglitazone on the liver histology and mitochondrial function in ob/ob mice. Hepatology46(2), 414–423 (2007).
   PubMed Web of Science ®Google Scholar
• Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N. Engl. J. Med.356(24), 2457–2471 (2007).
   PubMed Web of Science ®Google Scholar
• Singh S, Loke YK, Furberg CD. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA298(10), 1189–1195 (2007).
   PubMed Web of Science ®Google Scholar
• Dormandy JA, Charbonnel B, Eckland DJ et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet366(9493), 1279–1289 (2005).
   PubMed Web of Science ®Google Scholar
• Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients with Type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA298(10), 1180–1188 (2007).
   PubMed Web of Science ®Google Scholar
• Satapathy SK, Garg S, Chauhan R et al. Beneficial effects of tumor necrosis factor-α inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. Am. J. Gastroenterol.99(10), 1946–1952 (2004).
   PubMed Web of Science ®Google Scholar
• Adams LA, Zein CO, Angulo P, Lindor KD. A pilot trial of pentoxifylline in nonalcoholic steatohepatitis. Am. J. Gastroenterol.99(12), 2365–2368 (2004).
   PubMed Web of Science ®Google Scholar
• Kushner RF, Noble CA. Long-term outcome of bariatric surgery: an interim analysis. Mayo Clin. Proc.81(10 Suppl.), S46–S51 (2006).
   PubMedGoogle Scholar
• Charlton M, Kasparova P, Weston S et al. Frequency of nonalcoholic steatohepatitis as a cause of advanced liver disease. Liver Transpl.7(7), 608–614 (2001).
   PubMed Web of Science ®Google Scholar
• Contos MJ, Cales W, Sterling RK et al. Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis. Liver Transpl.7(4), 363–373 (2001).
   PubMed Web of Science ®Google Scholar
• Sass DA, Chang P, Chopra KB. Nonalcoholic fatty liver disease: a clinical review. Dig. Dis. Sci.50(1), 171–180 (2005).
   PubMed Web of Science ®Google Scholar
• Partin JS, Partin JC, Schubert WK, McAdams AJ. Liver ultrastructure in aβ-lipoproteinemia: Evolution of micronodular cirrhosis. Gastroenterology67(1), 107–118 (1974).
   PubMed Web of Science ®Google Scholar
• Wasserman JM, Thung SN, Berman R, Bodenheimer HC Jr, Sigal SH. Hepatic Weber–Christian disease. Semin. Liver Dis.21(1), 115–118 (2001).
   PubMedGoogle Scholar
• Mansouri A, Gaou I, Fromenty B et al. Premature oxidative aging of hepatic mitochondrial DNA in Wilson’s disease. Gastroenterology113(2), 599–605 (1997).
   PubMed Web of Science ®Google Scholar
• Van SW, Lanckmans S. Liver disturbances in obesity and diabetes mellitus. Int. J. Obes. Relat. Metab. Disord.19(Suppl. 3), S27–S36 (1995).
   Google Scholar
• Cassagnou M, Boruchowicz A, Guillemot F et al. Hepatic steatosis revealing celiac disease: a case complicated by transitory liver failure. Am. J. Gastroenterol.91(6), 1291–1292 (1996).
   PubMedGoogle Scholar
• Simon JB, Manley PN, Brien JF, Armstrong PW. Amiodarone hepatotoxicity simulating alcoholic liver disease. N. Engl. J. Med.311(3), 167–172 (1984).
   PubMed Web of Science ®Google Scholar
• Dahl MG, Gregory MM, Scheuer PJ. Liver damage due to methotrexate in patients with psoriasis. Br. Med. J.1(750), 625–630 (1971).
   PubMed Web of Science ®Google Scholar
• Cai Q, Bensen M, Greene R, Kirchner J. Tamoxifen-induced transient multifocal hepatic fatty infiltration. Am. J. Gastroenterol.95(1), 277–279 (2000).
   PubMed Web of Science ®Google Scholar
• Pinto HC, Baptista A, Camilo ME et al. Tamoxifen-associated steatohepatitis – report of three cases. J. Hepatol.23(1), 95–97 (1995).
   PubMed Web of Science ®Google Scholar
• Dourakis SP, Sevastianos VA, Kaliopi P. Acute severe steatohepatitis related to prednisolone therapy. Am. J. Gastroenterol.97(4), 1074–1075 (2002).
   PubMed Web of Science ®Google Scholar
• Cote HC, Brumme ZL, Craib KJ et al. Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV-infected patients. N. Engl. J. Med.346(11), 811–820 (2002).
   PubMed Web of Science ®Google Scholar
• Cotrim HP, Andrade ZA, Parana R et al. Nonalcoholic steatohepatitis: a toxic liver disease in industrial workers. Liver19(4), 299–304 (1999).
   PubMedGoogle Scholar
• Redlich CA, West AB, Fleming L et al. Clinical and pathological characteristics of hepatotoxicity associated with occupational exposure to dimethylformamide. Gastroenterology99(3), 748–757 (1990).
   PubMed Web of Science ®Google Scholar
• Cotrim H, Freitas LA, Freitas C et al. Nonalcoholic steatohepatitis in petrochemoical workers: follow up of those removed from exposure area and those who remained. Hepatology36, 983 (2002).
   Google Scholar
• Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Par 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet. Med.15(7), 539–553 (1998).
   PubMed Web of Science ®Google Scholar
• Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation106(25), 3143–3421 (2002).
   PubMed Web of Science ®Google Scholar
• Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation109(3), 433–438 (2004).
   PubMed Web of Science ®Google Scholar
• Grundy SM, Cleeman JI, Daniels SR et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation112(17), 2735–2752 (2005).
   PubMed Web of Science ®Google Scholar
• Maher JJ, Cores GJ, Lu SC. Mechanisms of liver injury due to fat. In: Liver Diseases. Mechanisms of Liver Injury in Emerging Therapeutics. American Association for the Study of the Liver Diseases, 89–96 (2006).
   Google Scholar
• Reid AE, Wright TL, Rocky DC. Nonalcoholic fatty liver disease. Diagnosis and clinical outcomes. In: Liver Disease: From Bench to Bedside. American Association for the Study of Liver Disease, 83–89 (2004).
   Google Scholar