New diagnostic and treatment approaches in non-alcoholic fatty liver disease (NAFLD)

References

• Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980; 55: 434–8
   PubMed Web of Science ®Google Scholar
• Powell EE, Cooksley WG, Hanson R, Searle J, Halliday JW, Powell LW. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. Hepatology. 1990; 11: 74–80
   PubMed Web of Science ®Google Scholar
• Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006; 44: 865–73
   PubMed Web of Science ®Google Scholar
• Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005; 129: 113–21
   PubMed Web of Science ®Google Scholar
• Targher G, Lorenzo B, Roberto P, Stefano R, Roberto T, Luciano Z, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care. 2007; 30: 1212–8
   PubMed Web of Science ®Google Scholar
• Targher G, Bertolini L, Poli F, Rodella S, Scala L, Tessari R, et al. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes. 2005; 54: 3541–6
   PubMed Web of Science ®Google Scholar
• Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology. 2002; 122: 1649–57
   PubMed Web of Science ®Google Scholar
• Wieckowska A, McCullough A, Feldstein A. Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future. Hepatology. 2007; 46: 582–9
   PubMed Web of Science ®Google Scholar
• Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004; 40: 1387–95
   PubMed Web of Science ®Google Scholar
• Frantzides CT, Carlson MA, Moore RE, Zografakis JG, Madan AK, Puumala S, et al. Effect of body mass index on nonalcoholic fatty liver disease in patients undergoing minimally invasive bariatric surgery. J Gastrointest Surg. 2004; 8: 849–55
   Google Scholar
• Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: A spectrum of clinical and pathological severity. Gastroenterology. 1999; 116: 1413–9
   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. 2003; 98: 960–7
   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. 2003; 98: 2042–7
   PubMed Web of Science ®Google Scholar
• Fassio E, Alvarez E, Domínguez N, Landeira G, Longo C. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology. 2004; 40: 820–6
   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. 2005; 42: 132–8
   PubMed Web of Science ®Google Scholar
• Marceau P, Biron S, Hould FS, Marceau S, Simard S, Thung SN, et al. Liver pathology and the metabolic syndrome X in severe obesity. J Clin Endocrinol Metab. 1999; 84: 1513–7
   PubMed Web of Science ®Google Scholar
• Luyckx FH, Desaive C, Thiry A, Dewe W, Scheen AJ, Gielsen JE, et al. Liver abnormalities in severely obese subjects: effects of drastic weight loss after gastroplasty. Int J Obes Relat Metab Disord. 1998; 22: 222–6
   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. Gastroenterology. 2001; 121: 91–100
   PubMed Web of Science ®Google Scholar
• Mofrad P, Contos MJ, Haque M, Sargeant C, Fisher RA, Luketic VA, et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology. 2003; 37: 1286–92
   PubMed Web of Science ®Google Scholar
• Sorrentino P, Tarantino G, Conca P, Perrella A, Terracciano ML, Vecchione R, et al. Silent non-alcoholic fatty liver disease–-a clinical-histological study. J Hepatol. 2004; 41: 751–7
   PubMed Web of Science ®Google Scholar
• Gholam PM, Flancbaum L, Machan JT, Charney DA, Kotler DP. Nonalcoholic fatty liver disease in severely obese subjects. Am J Gastroenterol. 2007; 102: 399–408
   PubMed Web of Science ®Google Scholar
• Amarapurkar D, Patel N. Clinical spectrum and natural history of non-alcoholic steatohepatitis with normal alanine aminotransferase values. Trop Gastroenterol. 2004; 25: 130–4
   PubMedGoogle Scholar
• Kunde S, Larenzby A, Clements R, Abrams G. Spectrum of NAFLD and diagnostic implications of the proposed new normal range for serum ALT in obese women. Hepatology. 2005; 42: 650–6
   PubMed Web of Science ®Google Scholar
• Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999; 30: 1356–62
   PubMed Web of Science ®Google Scholar
• Younossi ZM, Gramlich T, Matteoni CA, Boparai N, McCullough AJ. Nonalcoholic fatty liver disease in patients with type 2 diabetes. Clin Gastroenterol Hepatol. 2004; 2(3)262–5
   PubMed Web of Science ®Google Scholar
• Haukeland JW, Konopski Z, Linnestad P, Azimy S, Marit Loberg E, Haaland T, et al. Abnormal glucose tolerance is a predictor of steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease. Scand J Gastroenterol. 2005; 40: 1469–77
   PubMed Web of Science ®Google Scholar
• Maheshwari A, Paul JT. Cryptogenic cirrhosis and NAFLD: are they related?. Am J Gastroenterol. 2006; 101: 664–8
   PubMed Web of Science ®Google Scholar
• Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology. 1999; 29: 664–9
   PubMed Web of Science ®Google Scholar
• Hamaguchi M, Kojima T, Takeda N, Nagata C, Takeda J, Sarui H, et al. Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease. World J Gastroenterol. 2007; 13: 1579–84
   PubMed Web of Science ®Google Scholar
• Targher G, Bertolini L, Padovani R, Poli F, Scala L, Tessari R, et al. Increased prevalence of cardiovascular disease in Type 2 diabetic patients with non-alcoholic fatty liver disease. Diabet Med. 2006; 23: 403–9
   PubMed Web of Science ®Google Scholar
• Targher G. Non-alcoholic fatty liver disease, the metabolic syndrome and the risk of cardiovascular disease: the plot thickens. Diabet Med. 2007; 24: 1–6
   PubMed Web of Science ®Google Scholar
• Targher G, Bertolini L, Padovani R, Rodella S, Zoppini G, Zenari L, et al. Relations between carotid artery wall thickness and liver histology in subjects with nonalcoholic fatty liver disease. Diabetes Care. 2006; 29: 1325–30
   PubMed Web of Science ®Google Scholar
• Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest. 2004; 114: 147–52
   PubMed Web of Science ®Google Scholar
• Diehl AM, Li ZP, Lin HZ, Yang SQ. Cytokines and the pathogenesis of non-alcoholic steatohepatitis. Gut. 2005; 54: 303–6
   PubMedGoogle Scholar
• Pessayre D, Fromenty B. NASH: a mitochondrial disease. J Hepatol. 2005; 42: 928–40
   PubMed Web of Science ®Google Scholar
• Elsharkawy AM, Mann DA. Nuclear factor-kappaB and the hepatic inflammation-fibrosis-cancer axis. Hepatology. 2007; 46: 590–7
   PubMed Web of Science ®Google Scholar
• Carter-Kent C, Zein NN, Feldstein AE. Cytokines in the pathogenesis of fatty liver and disease progression to steatohepatitis: implications for treatment. Am J Gastroenterol. 2008; 103: 1036–42
   PubMed Web of Science ®Google Scholar
• Bogacka I, Xie H, Bray GA, Smith SR. The effect of pioglitazone on peroxisome proliferator-activated receptor-gamma target genes related to lipid storage in vivo. Diabetes Care. 2004; 27: 1660–7
   PubMed Web of Science ®Google Scholar
• Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006; 355: 2297–307
   PubMed Web of Science ®Google Scholar
• Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest. 2005; 115: 1343–51
   PubMed Web of Science ®Google Scholar
• Fromenty B, Robin M, Igoudjil A, Mansouri A, Pessayre D. The ins and outs of mitochondrial dysfunction in NASH. Diabetes Metab. 2004; 30: 121–38
   PubMed Web of Science ®Google Scholar
• Shimomura I, Bashmakov Y, Horton JD. Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus. J Biol Chem. 1999; 274: 30028–32
   PubMed Web of Science ®Google Scholar
• Yahagi N, Shimano H, Hasty AH, Matsuzaka T, Ide T, Yoshikawa T, et al. Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers but not obesity or insulin resistance in Lep(ob)/Lep(ob) mice. J Biol Chem. 2002; 277: 19353–7
   PubMed Web of Science ®Google Scholar
• Yu JG, Javorschi S, Hevener AL, Kruszynska YT, Norman RA, Sinha M, et al. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes. 2002; 51: 2968–74
   PubMed Web of Science ®Google Scholar
• Tiikkainen M, Hakkinen A-M, Korsheninnikova E, Nyman T, Makimattila S, Yki-Jarvinen H. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes. 2004; 53: 2169–76
   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. Hepatology. 2003; 38: 1008–17
   PubMed Web of Science ®Google Scholar
• Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T, et al. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology. 2004; 39: 188–96
   PubMed Web of Science ®Google Scholar
• Miyazaki Y, Mahankali A, Matsuda M, Mahankali S, Hardies J, Cusi K, et al. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2002; 87: 2784–91
   PubMed Web of Science ®Google Scholar
• Fryer LG, Parbu-Patel A, Carling D. The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem. 2002; 277: 25226–32
   PubMed Web of Science ®Google Scholar
• Saha AK, Avilucea PR, Ye JM, Assifi MM, Kraegen EW, Ruderman NB. Pioglitazone treatment activates AMP-activated protein kinase in rat liver and adipose tissue in vivo. Biochem Biophys Res Commun. 2004; 314: 580–5
   PubMed Web of Science ®Google Scholar
• Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 2002; 8: 1288–95
   PubMed Web of Science ®Google Scholar
• Bajaj M, Suraamornkul S, Piper P, Hardies LJ, Glass L, Cersosimo E, et al. Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated type 2 diabetic patients. J Clin Endocrinol Metab. 2004; 89: 200–6
   PubMed Web of Science ®Google Scholar
• Abbasi F, Chang SA, Chu JW, Ciaraldi TP, Lamendola C, McLaughlin T, et al. Improvements in insulin resistance with weight loss, in contrast to rosiglitazone, are not associated with changes in plasma adiponectin or adiponectin multimeric complexes. Am J Physiol Regul Integr Comp Physiol. 2006; 290: R139–44
   PubMed Web of Science ®Google Scholar
• Bugianesi E, Gastaldelli A, Vanni E, Gambino R, Cassader M, Baldi S, et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia. 2005; 48: 634–42
   PubMed Web of Science ®Google Scholar
• Gastaldelli A, Cusi K, Pettiti M, Hardies J, Miyazaki Y, Berria R, et al. Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects. Gastroenterology. 2007; 133: 496–506
   PubMed Web of Science ®Google Scholar
• Kaser S, Moschen A, Cayon A, Kaser A, Crespo J, Pons-Romero F, et al. Adiponectin and its receptors in non-alcoholic steatohepatitis. Gut. 2005; 54: 117–21
   PubMed Web of Science ®Google Scholar
• Cabrero A, Laguna JC, Vazquez M. Peroxisome proliferator-activated receptors and the control of inflammation. Curr Drug Targets Inflamm Allergy. 2002; 1: 243–8
   PubMedGoogle Scholar
• Murase K, Odaka H, Suzuki M, Tayuki N, Ikeda H. Pioglitazone time-dependently reduces tumour necrosis factor-( level in muscle and improves metabolic abnormalities in Wistar fatty rats. Diabetologia. 1998; 41: 257–64
   PubMed Web of Science ®Google Scholar
• Enomoto N, Takei Y, Hirose M, Konno A, Shibuya T, Matsuyama S, et al. Prevention of ethanol-induced liver injury in rats by an agonist of peroxisome proliferator-activated receptor-gamma, pioglitazone. J Pharmacol Exp Ther. 2003; 306: 846–54
   PubMed Web of Science ®Google Scholar
• Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: Summary of an AASLD Single Topic Conference. Hepatology. 2003; 37: 1202–19
   PubMed Web of Science ®Google Scholar
• Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002; 346: 1221–31
   PubMed Web of Science ®Google Scholar
• Ipekci SH, Basaranoglu M, Sonsuz A. The fluctuation of serum levels of aminotransferase in patients with nonalcoholic steatohepatitis. J Clin Gastroenterol. 2003; 36: 371
   PubMed Web of Science ®Google Scholar
• Gupte P, Amarapurkar D, Agal S, Baijal R, Kulshrestha P, Pramanik S, et al. Non-alcoholic steatohepatitis in type 2 diabetes mellitus. J Gastroenterol Hepatol. 2004; 19: 854–8
   PubMed Web of Science ®Google Scholar
• Hamaguchi M, Kojima T, Takeda N, Nakagawa T, Taniguchi H, Fujii K, et al. The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med. 2005; 143: 722–8
   PubMed Web of Science ®Google Scholar
• Palmentieri B, de Sio I, La Mura V, Masarone M, Vecchione R, Bruno S. The role of bright liver echo pattern on ultrasound B-mode examination in the diagnosis of liver steatosis. Dig Liver Dis. 2006; 38: 485–9
   PubMedGoogle Scholar
• Adams LA, Paul A. Role of liver biopsy and serum markers of liver fibrosis in non-alcoholic fatty liver disease. Clin Liver Dis. 2007; 11: 25–35
   Google Scholar
• Ryan CK, Johnson LA, Germin BI, Marcos A. One hundred consecutive hepatic biopsies in the workup of living donors for right lobe liver transplantation. Liver Transpl. 2002; 8: 1114–22
   PubMed Web of Science ®Google Scholar
• Limanond P, Raman SS, Lassman C, Sayre J, Ghobrial RM, Busuttil RW, et al. Macrovesicular hepatic steatosis in living related liver donors: correlation between CT and histologic findings. Radiology. 2004; 230: 276–80
   PubMed Web of Science ®Google Scholar
• Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002; 123: 745–50
   PubMed Web of Science ®Google Scholar
• Longo R, Pollesello P, Ricci C, Masutti F, Kvam BJ, Bercich L, et al. Proton MR spectroscopy in quantitative in vivo determination of fat content in human liver steatosis. J Magn Reson Imaging. 1995; 5: 281–5
   PubMed Web of Science ®Google Scholar
• Bajaj M, Suraamornkul S, Hardies J, Glass L, Musi N, Defronzo R. Effects of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma agonists on glucose and lipid metabolism in patients with type 2 diabetes mellitus. Diabetologia. 2007; 50: 1723–31
   PubMed Web of Science ®Google Scholar
• Thomsen C, Becker U, Winkler K, Christoffersen P, Jensen M, Henriksen O. Quantification of liver fat using magnetic resonance spectroscopy. Magn Reson Imaging. 1994; 12: 487–95
   PubMedGoogle Scholar
• Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, 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: E462–8
   PubMed Web of Science ®Google Scholar
• Szczepaniak LS, Babcock EE, Schick F, Dobbins RL, Garg A, Burns DK, et al. Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo. Am J Physiol. 1999; 276: E977–89
   Web of Science ®Google Scholar
• Noren B, Dahlqvist O, Lundberg P, Almer S, Kechagias S, Ekstedt M, et al. Separation of advanced from mild fibrosis in diffuse liver disease using 31P magnetic resonance spectroscopy. Eur J Radiol. 2008; 66: 313–20
   PubMed Web of Science ®Google Scholar
• Ohno A, Ohta Y, Ohtomo K, Hirata K, Takatsuki K, Mochida S, et al. Magnetic resonance imaging in chronic liver disease evaluated in relation to hepatic fibrosis–-clinical and experimental results. Radiat Med. 1990; 8: 159–63
   Google Scholar
• Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005; 41: 1313–21
   PubMed Web of Science ®Google Scholar
• Adams LA, Talwalkar JA. Diagnostic evaluation of nonalcoholic fatty liver disease. J Clin Gastroenterol. 2006; 40(Suppl 1)S34–8
   Google Scholar
• Keeffe EB, Adesman PW, Stenzel P, Palmer RM. Steatosis and cirrhosis in an obese diabetic. Resolution of fatty liver by fasting. Dig Dis Sci. 1987; 32: 441–5
   Google Scholar
• Andersen T, Gluud C, Franzmann MB, Christoffersen P. Hepatic effects of dietary weight loss in morbidly obese subjects. J Hepatol. 1991; 12: 224–9
   PubMed Web of Science ®Google Scholar
• Shaffer E. Bariatric surgery: a promising solution for nonalcoholic steatohepatitis in the very obese. J Clin Gastroenterol. 2006; 40: S44–50
   PubMedGoogle Scholar
• Dixon JB, Bhathal PS, Hughes NR, O'Brien PE. Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss. Hepatology. 2004; 39: 1647–54
   PubMed Web of Science ®Google Scholar
• Klein S, Mittendorfer B, Eagon JC, Patterson B, Grant L, Feirt N, et al. Gastric bypass surgery improves metabolic and hepatic abnormalities associated with nonalcoholic fatty liver disease. Gastroenterology. 2006; 130: 1564–72
   PubMed Web of Science ®Google Scholar
• Mathurin P, Gonzalez F, Kerdraon O, Leteurtre E, Arnalsteen L, Hollebecque A, et al. The evolution of severe steatosis after bariatric surgery is related to insulin resistance. Gastroenterology. 2006; 130: 1617–24
   PubMed Web of Science ®Google Scholar
• Sjostrom L, Narbro K, Sjostrom CD, Karason K, Larsson B, Wedel H, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007; 357: 741–52
   PubMed Web of Science ®Google Scholar
• Adams TD, Gress RE, Smith SC, Halverson RC, Simper SC, Rosamond WD, et al. Long-term mortality after gastric bypass surgery. N Engl J Med. 2007; 357: 753–61
   PubMed Web of Science ®Google Scholar
• Wang R, Koretz R, Yee H. Is weight reduction an effective therapy for nonalcoholic fatty liver? A systematic review. Am J Med. 2003; 115: 554–9
   PubMed Web of Science ®Google Scholar
• Zivkovic AM, German JB, Sanyal AJ. Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease. Am J Clin Nutr. 2007; 86: 285–300
   PubMed Web of Science ®Google Scholar
• Harrison SA, Day CP. Benefits of lifestyle modification in NAFLD. Gut. 2007; 56: 1760–9
   PubMed Web of Science ®Google Scholar
• Palmer M, Schaffner F. Effect of weight reduction on hepatic abnormalities in overweight patients. Gastroenterology. 1990; 99: 1408–13
   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. 1995; 10: 414–21
   PubMedGoogle Scholar
• Ueno T, Sugawara H, Sujaku K, Hashimoto O, Tsuji R, Tamaki S, et al. Therapeutic effects of restricted diet and exercise in obese patients with fatty liver. J Hepatol. 1997; 27: 103–7
   PubMed Web of Science ®Google Scholar
• Kugelmas M, Hill DB, Vivian B, Marsano L, McClain CJ. Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. Hepatology. 2003; 38: 413–9
   PubMed Web of Science ®Google Scholar
• Sreenivasa Baba C, Alexander G, Kalyani B, Pandey R, Rastogi S, Pandey A, et al. Effect of exercise and dietary modification on serum aminotransferase levels in patients with nonalcoholic steatohepatitis. J Gastroenterol Hepatol. 2006; 21: 191–8
   PubMed Web of Science ®Google Scholar
• Tamura Y, Tanaka Y, Sato F, Choi JB, Watada H, Niwa M, et al. Effects of diet and exercise on muscle and liver intracellular lipid contents and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2005; 90: 3191–6
   PubMed Web of Science ®Google Scholar
• Westerbacka J, Lammi K, Hakkinen AM, Rissanen A, Salminen I, Aro A, et al. Dietary fat content modifies liver fat in overweight nondiabetic subjects. J Clin Endocrinol Metab. 2005; 90: 2804–9
   PubMed Web of Science ®Google Scholar
• Petersen KF, Dufour S, Befroy D, Lehrke M, Hendler RE, Shulman GI. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes. 2005; 54: 603–8
   PubMed Web of Science ®Google Scholar
• Huang MA, Greenson JK, Chao C, Anderson L, Peterman D, Jacobson J, et al. One-year intense nutritional counseling results in histological improvement in patients with non–alcoholic steatohepatitis: a pilot study. Am J Gastroenterol. 2005; 100: 1072–81
   PubMed Web of Science ®Google Scholar
• Browning JD, Davis J, Saboorian MH, Burgess SC. A low-carbohydrate diet rapidly and dramatically reduces intrahepatic triglyceride content. Hepatology. 2006; 44: 487–8
   Google Scholar
• Tendler D, Lin S, Jr, Yancy WS, Mavropoulos J, Sylvestre P, Rockey DC, et al. The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study. Dig Dis Sci. 2007; 52: 589–93
   PubMed Web of Science ®Google Scholar
• Ryan MC, Abbasi F, Lamendola C, Carter S, McLaughlin TL. Serum alanine aminotransferase levels decrease further with carbohydrate than fat restriction in insulin-resistant adults. Diabetes Care. 2007; 30: 1075–80
   Google Scholar
• Bugianesi E, Marzocchi R, Villanova N, Marchesini G. Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH): treatment. Best Pract Res Clin Gastroenterol. 2004; 18: 1105–16
   PubMed Web of Science ®Google Scholar
• Crespo J, Cayon A, Fernandez-Gil P, Hernandez-Guerra M, Mayorga M, Dominguez-Diez A, et al. Gene expression of tumor necrosis factor alpha and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients. Hepatology. 2001; 34: 1158–63
   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. 2004; 99: 2365–8
   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. 2003; 98: 2485–90
   PubMed Web of Science ®Google Scholar
• Harrison SA, Ramrakhiani S, Brunt EM, Anbari MA, Cortese C, Bacon BR. Orlistat in the treatment of NASH: a case series. Am J Gastroenterol. 2003; 98: 926–30
   PubMed Web of Science ®Google Scholar
• Zelber-Sagi S, Kessler A, Brazowsky E, Webb M, Lurie Y, Santo M, et al. A double-blind randomized placebo-controlled trial of orlistat for the treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2006; 4: 639–44
   PubMed Web of Science ®Google Scholar
• Laurin J, Lindor KD, Crippin JS, Gossard A, Gores GJ, Ludwig J, et al. Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: a pilot study. Hepatology. 1996; 23: 1464–7
   PubMed Web of Science ®Google Scholar
• Dufour JF, Oneta CM, Gonvers JJ, Bihl F, Cerny A, Cereda JM, et al. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2006; 4: 1537–43
   PubMed Web of Science ®Google Scholar
• Lindor KD, Kowdley KV, Heathcote EJ, Harrison ME, Jorgensen R, Angulo P, et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology. 2004; 39: 770–8
   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. 2001; 96: 2711–7
   PubMed Web of Science ®Google Scholar
• Zandbergen AA, Lamberts SW, Janssen JA, Bootsma AH. Short-term administration of an angiotensin-receptor antagonist in patients with impaired fasting glucose improves insulin sensitivity and increases free IGF-I. Eur J Endocrinol. 2006; 155: 293–6
   Google Scholar
• Yokohama S, Tokusashi Y, Nakamura K, Tamaki Y, Okamoto S, Okada M, et al. Inhibitory effect of angiotensin II receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis. World J Gastroenterol. 2006; 12: 322–6
   PubMed Web of Science ®Google Scholar
• Yokohama S, Yoneda M, Haneda M, Okamoto S, Okada M, Aso K, et al. Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology. 2004; 40: 1222–5
   PubMed Web of Science ®Google Scholar
• Cusi K, DeFronzo R. Metformin: a review of its metabolic effects. Diabetes Rev. 1998; 6: 89–131
   Google Scholar
• Cusi K, Consoli A, DeFronzo RA. Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1996; 81: 4059–67
   PubMed Web of Science ®Google Scholar
• Towler M, Hardie D. AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res. 2007; 100: 328–41
   PubMed Web of Science ®Google Scholar
• Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M, Melchionda N. Metformin in non-alcoholic steatohepatitis. Lancet. 2001; 358: 893–4
   PubMed Web of Science ®Google Scholar
• Uygun A, Kadayifci A, Isik AT, Ozgurtas T, Deveci S, Tuzun A, et al. Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2004; 19: 537–44
   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. 2004; 20: 23–8
   PubMed Web of Science ®Google Scholar
• Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N, et al. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol. 2005; 100: 1082–90
   PubMed Web of Science ®Google Scholar
• Caldwell SH, Hespenheide EE, Redick JA, Iezzoni JC, Battle EH, Sheppard BL. A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis. Am J Gastroenterol. 2001; 96: 519–25
   PubMed Web of Science ®Google Scholar
• Sanyal AJ, Mofrad PS, Contos MJ, Sargeant C, Luketic VA, Sterling RK, et al. A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2004; 2: 1107–15
   PubMed Web of Science ®Google Scholar
• Serfaty L. Pioglitazone: the beginning of a new era for NASH?. J Hepatol. 2007; 47: 160–2
   Google Scholar
• Lang L. Pioglitazone trial for NASH: results show promise. Gastroenterology. 2007; 132: 836–8
   Google Scholar