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Management and diagnosis of fatty liver disease

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References

  • Abdelmalek M, Ludwig J, Lindor KD. Two cases from the spectrum of nonalcoholic steatohepatitis. J Clin Gastroenterol 1995;20:127-30
  • Brunt EM. Nonalcoholic steatohepatitis: pathologic features and differential diagnosis. Semin Diagn Pathol 2005;22:300-38
  • Brunt EM, Tiniakos DG. Alcoholic and nonalcoholic fatty liver disease. In: Odze RD, Goldblum JR, editors. Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas. 2nd edition. Elsevier; Philadelphis, PA: 2009. p. 1007-14
  • Ludwig J, Viggiano TR, McGill DB, et al. Nonalcoholic steatohepatitis: mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980;55:434-8
  • Younossi ZM, Stepanova M, Afendy M, et al. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol 2011;9:524-30
  • Argo CK, Caldwell SH. Epidemiology and natural history of non-alcoholic steatohepatitis. Clin Liver Dis 2009;13:511-31
  • Lazo M, Hernandez R, Eberhardt MS, et al. Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1998-1994. Am J Epidemiol 2013;178(1):38-45
  • Bedogni G, Miglioli L, Masutti F, et al. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 2005;42:44-52
  • Caballería L, Pera G, Auladell MA, et al. Prevalence and factors associated with the presence of nonalcoholic fatty liver disease in an adult population in Spain. Eur J Gastroenterol Hepatol 2010;22:24-32
  • Bedogni G, Bellentani S. Fatty liver: how frequent is it and why? Ann Hepatol 2004;3:63-5
  • Williams CD, Stengel J, Asike MI, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 2011;140(1):124-31
  • Kojima SI, Watanabe N, Numata M, et al. Increase in the prevalence of fatty liver in Japan over the past 12 years: analysis of clinical background. J Gastroenterol 2003;38:954-61
  • Amarapurkar D, Kamani P, Patel N, et al. Prevalence of non-alcoholic fatty liver disease: population based study. Ann Hepatol 2007;6:161-3
  • Fan JG, Farrell GC. Epidemiology of non-alcoholic fatty liver disease in China. J Hepatol 2009;50:204-10
  • Yamamoto K, Takada Y, Fujimoto Y, et al. Nonalcoholic steatohepatitis in donors for living donor liver transplantation. Transplantation 2007;83:257-62
  • Lee JY, Kim KM, Lee SG, et al. Prevalence and risk factors of non-alcoholic fatty liver disease in potential living liver donors in Korea: a review of 589 consecutive liver biopsies in a single center. J Hepatol 2007;47:239-44
  • Reha JL, Lee S, Hofmann LJ. Prevalence and predictors of nonalcoholic steatohepatitis in obese patients undergoing bariatric surgery: a department of defense experience. Am Surg 2014;80(6):595-9
  • Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40:1387-95
  • Weston SR, Leyden W, Murphy R, et al. Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease. Hepatology 2005;41:372-9
  • Younossi ZM, Stepanova M, Negro F, et al. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine (Baltimore) 2012;91:319-27
  • Adams LA, Lymp JF, St Sauver J, et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005;129:113-21
  • Kallwitz ER, Kumar M, Aggarwal R, et al. Ethnicity and nonalcoholic fatty liver disease in an obesity clinic: the impact of triglycerides. Dig Dis Sci 2008;53:1358-63
  • Schneider AL, Lazo M, Selvin E, Clark JM. Racial differences in nonalcoholic fatty liver disease in the U.S. population. Obesity (Silver Spring) 2014;22:292-9
  • Smits MM, Ioannou GN, Boyko EJ, et al. Non-alcoholic fatty liver disease as an independent manifestation of the metabolic syndrome: results of a US national survey in three ethnic groups. J Gastroenterol Hepatol 2013;28:664-7
  • Fallon MB, Pan JJ. Gender and racial differences in nonalcoholic fatty liver disease. World J Hepatol 2014;6(5):274-83
  • Casas YG, Schiller BC, DeSouza CA, et al. Total and regional body composition across age in healthy hispanic and white women of similar socioeconomic status. Am J Clin Nutr 2001;73:13-18
  • Miyazaki Y, Glass L, Triplitt C, et al. Abdominal fat distribution and peripheral and hepatic insulin resistance in type 2 diabetes mellitus. Am J Physiol Endocrinol Metab 2002;283:E1135-43
  • Van der Poorten D, Milner KL, Hui J, et al. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology 2008;48:449-57
  • Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008;40:1461-5
  • Sookoian S, Pirola CJ. Meta-analysis of the influence of I148M variant of patatin-like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 2011;53:1883-94
  • Liu YL, Patman GL, Leathart JB, et al. Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol 2014;61(1):75-81
  • Guerrero R, Vega GL, Grundy SM, et al. Ethnic differences in hepatic steatosis: an insulin resistance paradox. Hepatology 2009;49:791-01
  • Wagenknecht LE, Scherzinger AL, Stamm ER, et al. Correlates and heritability of nonalcoholic fatty liver disease in a minority cohort. Obesity (Silver Spring) 2009;17:1240-6
  • Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003;37:917-23
  • 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. Hepatology 1990;11:74-80
  • Marchesini G, Brizi M, Bianchi G, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001;50(8):1844-50
  • Angelico F, Del Ben M, Conti R, et al. Non-alcoholic fatty liver syndrome: a hepatic consequence of common metabolic diseases. J Gastroenterol Hepatol 2003;18:1115-17
  • Bugianesi E, Gastaldelli A, Vanni E, et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia 2005;48(4):634-42
  • Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science 2011;332(6037):1519-23
  • Brown MS, Goldstein JL. Selective versus total insulin resistance: a pathogenic paradox. Cell Metab 2008;7(2):95-6
  • Marchesini G, Brizi M, Bianchi G, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001;50(8):1844-50
  • Musso G, Gambino R, De Michieli F, et al. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 2003;37(4):909-16
  • Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346(16):1221
  • Neuschwander-Tetri BA. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites. Hepatology 2010;52(2):774-88
  • Sanyal AJ, Campbell-Sargent C, Mirshahi F, et al. Nonacloholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001;120(5):1183
  • Cani PD, Possemiers S, Van de Wiele T, et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 2009;58:1091-03
  • Miele L, Valenza V, La Torre G, et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology 2009;49:1877-87
  • Brun P, Castagliuolo I, Di Leo V, et al. Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 2007;292:G518-25
  • Wigg AJ, Roberts-Thomson IC, Dymock RB, et al. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis. Gut 2001;48:206-11
  • Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology 2014;146(6):1513-24
  • Targher G, Bertolini L, Rodella S, et al. Associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease. Clin Endocrinol 2006;64:679-83
  • Bianchi G, Bugianesi E, Frystyk J, et al. Adiponectin isoforms, insulin resistance and liver histology in nonalcoholic fatty liver disease. Dig Liver Dis 2011;43:73-7
  • Hui JM, Hodge A, Farrell GC, et al. Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 2004;40:46-54
  • Larter CZ, Farrell GC. Insulin resistance, adiponectin, cytokines in NASH: which is the best target to treat? J Hepatol 2006;44(2):253-61
  • Polyzos SA, Toulis KA, Goulis DG, et al. Serum total adiponectin in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Metabolism 2011;60(3):313-26
  • Pasarin M, La Mura V, Gracia-Sancho J, et al. Sinusoidal endothelial dysfunction precedes inflammation and fibrosis in a model of NAFLD. PLoS One 2012;7(4):e32785
  • Francque S, Lalwman W, Verbeke L, et al. Increased intrahepatic resistance in severe steatosis: endothelial dysfunction, vasoconstrictor overprodution and altered microvascular architecture. Lab Invest 2012;92(10):1428-39
  • Li L, Chen L, Hu L, et al. Nuclear factor high-mobility group box1 mediating the activation of Toll-like receptor 4 signaling in hepatocytes in the early stage of nonalcoholic fatty liver disease in mice. Hepatology 2011;54(5):1620-30
  • Tajiri K, Shimizu Y, Tsuneyama K, et al. Role of liver-infiltrating CD3+CD56+ natural killer T cells in the pathogenesis of nonalcoholic fatty liver disease. Eur J Gatroenterol Hepatol 2009;21(6):673
  • Guy CD, Suzuki A, Zdanowicz M, et al. Hedgehog pathway activation parallels histologic severity of injury and fibrosis in human nonalcoholic fatty liver disease. Hepatology 2012;55(6):1711-21
  • Syn WK, Choi SS, Liaskou E, et al. Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis. Hepatology 2011;53(1):106-15
  • Diehl AM. Tumor necrosis factor and its potential role in insulin resistance and nonalcoholic fatty liver disease. Clin Liver Dis 2004;8:619-38
  • Rensen SS, Slaats Y, Nijhuis J, et al. Increased hepatic myeloperoxidase activity in obese subjects with nonalcoholic steatohepatitis. Am J Pathol 2009;175(4):1473-82
  • Rensen SS, Slaats Y, Driessen A, et al. Activation of the complement system in human nonalcoholic fatty liver disease. Hepatology 2009;50(6):1809-17
  • Hernandez-Gea V, Friedman SL. Pathogenesis of liver fibrosis. Annu Rev Pathol 2011;6:425-56
  • Poynard T, Mathurin P, Lai CL, et al. A comparison of fibrosis progression in chronic liver diseases. J Hepatol 2003;38:257
  • Schuppan D, Afdhal NH. Liver Cirrhosis. Lancet 2008;371(9615):838-51
  • Pais R, Charlotte F, Fedchuk L, et al. A systematic review of follow-up biopsies reveals disease progression in patients with non-alcoholic fatty liver. J Hepatol 2013;59(3):550-6
  • Wong VW, Wong GL, Choi PC, et al. Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut 2010;59(7):969-74
  • Torres DM, Williams CD, Harrison SA. Features, diagnosis, and treatment of nonalcoholic fatty liver disease. Clin Gastroent and Hepatol 2012;10(8):837-58
  • Sorrentino P, Tarantino G, Conca P, et al. Silent non-alcoholic fatty liver disease-a clinical-histological study. J Hepatol 2004;41:751-7
  • Argo CK, Northup PG, Al-Osaimi AM, et al. Systematic review of risk factors for fibrosis progression in non-alcoholic steatohepatitis. J Hepatol 2009;51(2):371-9
  • Hui AY, Wong VW, Chan HL, et al. Histological progression of non-alcoholic fatty liver disease in Chinese patients. Aliment Pharmacol Ther 2005;21:407-13
  • Fassio E, Alvarez E, Domínguez N, et al. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology 2004;40:820-6
  • Singh S, Allen AM, Wang Z, et al. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol 2014. [Epub ahead of print]
  • Valenti L, Al-Serri A, Daly AK, et al. Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 2010;51(4):1209-17
  • Angulo P, Keach AC, Batts KB, et al. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999;30(6):1356
  • Noureddin M, Yates KP, Vaughn IA, et al. Clinical and histological determinants of nonalcoholic steatohepatitis and advanced fibrosis in elderly patients. Hepatology 2013;58(5):1644-54
  • Hossain N, Afendy A, Stepanova M, et al. Independent predictors of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009;7(11):1224-9
  • Petta S, Amato MC, Di Marco V, et al. Visceral adiposity index is associated with significant fibrosis in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2012;35(2):238-47
  • Matteoni CA, Younossi ZM, Gramlich T, et al. Non alcoholic fatty liver disease (a spectrum of clinical and pathological severity). Gastroenterology 1999;116:1413-19
  • Harrison SA, Torgerson S, Hayashi PH. The natural history of non alcoholic fatty liver disease (a clinical histopathological study). Am J Gastroenterol 2003;98:2042-7
  • Dam-Larsen S, Franzmann M, Andersen IB, et al. Long term prognosis of fatty liver (risk of chronic liver disease and death). Gut 2004;53:750-5
  • Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006;44:865-73
  • Söderberg C, Stål P, Askling J, et al. Decreased survival of subjects with elevated liver function tests during a 28- year follow-up. Hepatology 2010;51:595-02
  • Rafiq N, Bai C, Fang Y, et al. Longterm follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol 2009;7:234-8
  • Hamaguchi M, Kojima T, Takeda N, et al. Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease. World J Gastroenterol 2007;13:1579-84
  • Bhala N, Angulo P, van der Poorten D, et al. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Hepatology 2011;54:1208-16
  • 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;30:1212-18
  • Haring R, Wallaschofski H, Nauck M, et al. Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma-glutamyl-transpeptidase levels. Hepatology 2009;50:1403-11
  • Vanwagner LB, Bhave M, Te HS, et al. Patients transplanted for nonalcoholic steatohepatitis are at increased risk for postoperative cardiovascular events. Hepatology 2012;56(5):1741-50
  • El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007;132:2557-76
  • Hashimoto E, Yatsuji S, Tobari M, et al. Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. J Gastroenterol 2009;44:89-95
  • Paredis V, Zalinski S, Chelbi E, et al. Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: a pathological analysis. Hepatology 2009;49(3):851-9
  • Cotrim HP, Parana R, Braga E, et al. Nonalcoholic steatohepatitis and hepatocellular carcinoma: natural history? Am J Gastroenterol 2000;44:3018-19
  • Zen Y, Katayanagi K, Tsuneyama K, et al. Hepatocellular carcinoma arising in non-alcoholic steatohepatitis. Pathol Int 2001;51:127-31
  • Mori S, Yamasaki T, Sakaida I, et al. Hepatocellular carcinoma with nonalcoholic steatohepatitis. J Gastroenterol 2004;39:391-6
  • Yoshioka Y, Hashimoto E, Yatsuji S, et al. Nonalcoholic steatohepatitis: cirrhosis, hepatocellular carcinoma and burn-out NASH. J Gastroenterol 2004;39:1215-18
  • Bullock RE, Zaitoun AM, Aithal GP, et al. Association of non-alcoholic steatohepatitis without significant fibrosis with hepatocellular carcinoma. J Hepatol 2004;41:685-90
  • Shimada M, Hashimoto E, Taniai M, et al. Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. J Hepatol 2002;37:154-60
  • Ong JP, Pitts A, Younossi ZM. Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol 2008;9:608-12
  • Amarapurkar DN, Dharod M, Gautam S, et al. Risk of development of hepatocellular carcinoma in patients with NASH-related cirrhosis. Trop Gastroenterol 2013;34(3):159-63
  • Ascha MS, Hanouneh IA, Lopez R, et al. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 2010;51(6):1972-8
  • Ratziu VD, Bonyhay L, Di Martino V, et al. Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis. Hepatology 2002;35:1485-93
  • Calle EE, Rodriguez C, Walker-Thurmond K, et al. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003;348:1625-38
  • Moller H, Mellemgaard A, Lindvig K, et al. Obesity and cancer risk: a Danish record-linkage study. Eur J Cancer 1994;30A:344-50
  • El-Serag HB, Hampel H, Javadi F. The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 2006;4:369-80
  • 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. Hepatology 2002;36:1349-54
  • Bugianesi E, Leone N, Vanni E, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002;123:134-40
  • Regimbeau JM, Colombat M, Mognol P, et al. Obesity and diabetes as a risk factor for hepatocellular carcinoma. Liver Transpl 2004;10(2):S69-73
  • Hui JM, Kench JG, Chitturi S, et al. Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C. Hepatology 2003;38(2):420-7
  • White DL, Kanwal F, El-Sarag H. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gantroenterol Hepatol 2012;10(12):1342
  • Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012;55:2005-23
  • Hernaez R, Lazo M, Bonekamp S, et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology 2011;54:1082
  • Mottin CC, Moretto M, Padoin AV, et al. The role of ultrasound in the diagnosis of hepatic steatosis in morbidly obese patients. Obes Surg 2004;14(5):635-7
  • Cho CS, Curran S, Schwartz LH, et al. Preoperative radiographic assessment of hepatic steatosis with histologic correlation. J Am Coll Surg 2008;206(3):480
  • Kwok R, Tse YK, Wong GL, et al. Systematic review with meta-analysis: non-invasive assessment of non-alcoholic fatty liver disease – the role of transient elastography and plasma cytokeratin-18 fragments. Aliment Pharmacol Ther 2014;39(3):254-69
  • Shi KQ, Tang JZ, Zhu XL, et al. Controlled attenuation parameter for the detection of steatosis severity in chronic liver disease: a meta-analysis of diagnostic accuracy. J Gastroenterol Hepatol 2014;29(6):1149-58
  • Tang A, Tan J, Sun M, et al. Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis. Radiology 2013;267(2):422-31
  • Idilman IS, Aniktar H, Idilman R, et al. Hepatic steatosis: quantification by proton density fat fraction with MR imaging versus liver biopsy. Radiology 2013;267(3):767-75
  • Schwenzer NF, Springer F, Schraml C, et al. Non-invasive assessment and quantification of liver steatosis by ultrasound, computed tomography and magnetic resonance. J Hepatol 2009;51:433
  • Neuschwander-Tetri BA, Clark JM, Bass NM, et al. Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology 2010;52:913
  • Musso G, Gambino R, Cassader M, et al. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med 2011;43(8):617-49
  • Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313
  • Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010;51:121
  • Andersen T, Gluud C, Franzmann MB, et al. Hepatic effects of dietary weight loss in morbidly obese subjects. J Hepatol 1991;12:224
  • Lavine JE. Vitamin E treatment of nonalcoholic steatohepatitis in children: a pilot study. J Pediatr 2000;136:734
  • Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010;362:1675-85
  • Belfort R, Harrison SA, Brown K, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006;355:2297
  • Aithal GP, Thomas JA, Kaye PV, et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology 2008;135:1176
  • Ratziu V, Giral P, Jacqueminet S, et al. Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology 2008;135:100
  • Boettcher E, Csako G, Pucino F, et al. Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2012;35:66
  • Neumann A, Weill A, Ricordeau P, et al. Pioglitazone and risk of bladder cancer among diabetic patients in France: a population-based cohort study. Diabetologia 2012;55:1953
  • Rakoski MO, Singal AG, Rogers MA, et al. Meta-analysis: insulin sensitizers for the treatment of non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2010;32:1211
  • Xu F, Li Z, Zheng X, et al. SIRT1 Mediates the Effect of GLP-1 receptor agonist exenatide on ameliorating hepatic steatosis. Diabetes 2014;63(11):3637-46
  • Bellentani S. Immunomodulating and anti-apoptotic action of ursodeoxycholic acid: where are we and where should we go? Eur J Gastroenterol Hepatol 2005;17:137
  • Lindor KD, Kowdley KV, Heathcote EJ, et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 2004;39:770
  • Leuschner UF, Lindenthal B, Herrmann G, et al. High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized, placebo-controlled trial. Hepatology 2010;52(2):472-9
  • Pietu F, Guillaud O, Walter T, et al. Ursodeoxycholic acid with vitamin E in patients with nonalcoholic steatohepatitis: long-term results. Clin Res Hepatol Gastroenterol 2012;36:146
  • 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 2006;4(5):639
  • Merat S, Malekzadeh R, Sohrabi MR, et al. Probucol in the treatment of non-alcoholic steatohepatitis: a double-blind randomized controlled study. J Hepatol 2003;38(4):414
  • Abdelmalek MF, Sanderson SO, Angulo P, et al. Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial. Hepatology 2009;50(6):1818
  • Foster T, Budoff MJ, Saab S, et al. Atorvastatin and antioxidants for the treatment of nonalcoholic fatty liver disease: the St Francis Heart Study randomized clinical trial. Am J Gastroenterol 2011;106(1):71
  • Van Wagner LB, Koppe SW, Brunt EM, et al. Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial. Ann Hepatol 2011;10(3):277-86
  • Chachay VS, Macdonald GA. Martin, JH, et al. Resveratrol does not benefit patientswith non-alcoholic fatty liver disease. Clin Gastroenterol Hepatol 2014;12(12):2092-103
  • Sanyal A, Abdelmalek M, Suzuki A, et al. No significant Effects of Ethyl-Eicosapentoic Acid on Histologic Features of Nonalcoholic Steatohepatitis in a Phase 2 Trial. Gastroenterology 2014;147(2):377-84
  • Scorletti E, Bhatia L, McCormick KG, et al. Design and rationale of the WELCOME trial: a randomised, placebo controlled study to test the efficacy of purified long chain omega-3 fatty treatment in non-alcoholic fatty liver disease. Contemp Clin Trials 2014;37(2):301-11
  • Angulo P. NAFLD, obesity, and bariatric surgery. Gastroenterology 2006;130:1848-52
  • Furuya CKJr, de Oliveira CP, de Mello ES, et al. Effects of bariatric surgery on nonalcoholic fatty liver disease: preliminary findings after 2 years. J Gastroenterol Hepatol 2007;22(4):510
  • Mathurin P, Hollebecque A, Arnalsteen L, et al. Prospective study of the long-term effects of bariatric surgery on liver injury in patients without advanced disease. Gastroenterology 2009;137(2):532-40
  • Chavez-Tapia NC, Tellez-Avili FI, Barrientos-Gutierrez T, et al. Bariatric surgery for nonalcoholic steatohepatitis in obese patients. Cochrane Database Syst Rev 2010(1):CD007340
  • Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003;362:1907-17
  • Kansagara D, Papak J, Pasha AS, et al. Screening for hepatocellular carcinoma in chronic liver disease: a systematic review. Ann Intern Med 2014;161(4):261-9
  • Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 2004;130:417-22
  • Chen JG, Parkin DM, Chen QG, et al. Screening for liver cancer: results of a randomised controlled trial in Qidong. China. J Med Screen 2003;10:204-9
  • Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. AASLD Practise Guideline 2011(3):1020-2
  • Wang YC, McPherson K, Marsh T, et al. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet 2011;378(9793):815-25
  • McCullough AJ, Dasarathy S. Nonalcoholic Fatty Liver Disease. In: Hawkey CJ, Bosch J, Richter JE, et al. editors. Textbook of Clinical Gastroenterology and Hepatology. John Wiley and Sons, Ltd; Chichester, West Sussex: 2012

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