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Review

Diagnosis and management of cardiovascular risk in nonalcoholic fatty liver disease

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References

  • Loria P, Marchesini G, Nascimbeni F, et al. Cardiovascular risk, lipidemic phenotype and steatosis. A comparative analysis of cirrhotic and non-cirrhotic liver disease due to varying etiology. Atherosclerosis 2014;232(1):99-109
  • Loria P, Adinolfi LE, Bellentani S, et al. Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease. A decalogue from the Italian Association for the Study of the Liver (AISF) Expert Committee. Dig Liver Dis 2010;42(4):272-82
  • Lonardo A, Sookoian S, Chonchol M, et al. Cardiovascular and systemic risk in nonalcoholic fatty liver disease - atherosclerosis as a major player in the natural course of NAFLD. Curr Pharm Des 2013;19(29):5177-92
  • Ballestri S, Lonardo A, Bonapace S, et al. Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease. World J Gastroenterol 2014;20(7):1724-45
  • Bertolotti M, Lonardo A, Mussi C, et al. NAFLD and aging: epidemiology to management. World J Gastroenterol 2014; In press
  • Loria P, Lonardo A, Targher G. Is liver fat detrimental to vessels?: intersections in the pathogenesis of NAFLD and atherosclerosis. Clin Sci (Lond) 2008;115(1):1-12
  • Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 2013;10(6):330-44
  • Oni ET, Agatston AS, Blaha MJ, et al. A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care? Atherosclerosis 2013;230(2):258-67
  • Nascimbeni F, Pais R, Bellentani S, et al. From NAFLD in clinical practice to answers from guidelines. J Hepatol 2013;59(4):859-71
  • Matteoni CA, Younossi ZM, Gramlich T, et al. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999;116(6):1413-19
  • 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(5):750-5
  • 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(1):113-21
  • Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006;44(4):865-73
  • Rafiq N, Bai C, Fang Y, et al. Long-term follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol 2009;7(2):234-8
  • 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(2):595-602
  • Musso G, Gambino R, Cassader M, Pagano G. 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
  • Sookoian S, Gianotti TF, Rosselli MS, et al. Liver transcriptional profile of atherosclerosis-related genes in human nonalcoholic fatty liver disease. Atherosclerosis 2011;218(2):378-85
  • Ballestri S, Lonardo A, Romagnoli D, et al. Ultrasonographic fatty liver indicator, a novel score which rules out NASH and is correlated with metabolic parameters in NAFLD. Liver Int 2012;32(8):1242-52
  • NIH. Available from: http://cvdrisk.nhlbi.nih.gov
  • Targher G, Bertolini L, Padovani R, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007;30(5):1212-18
  • Greenland P, Alpert JS, Beller GA, et al. 2010;ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2010;122(25):e584-636
  • Perk J, De Backer G, Gohlke H, et al. European Guidelines on cardiovascular disease prevention in clinical practice. The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Atherosclerosis 2012;223(1):1-68
  • American diabetes Association. Standards of medical care in diabetes – 2014. Diabetes Care 2014;37(Suppl 1):S14-80
  • Treeprasertsuk S, Leverage S, Adams LA, et al. The Framingham risk score and heart disease in nonalcoholic fatty liver disease. Liver Int 2012;32(6):945-50
  • Eichler K, Puhan MA, Steurer J, Bachmann LM. Prediction of first coronary events with the Framingham score: a systematic review. Am Heart J 2007;153(5):722-31
  • Palmieri L, Panico S, Vanuzzo D, Gruppo di Ricerca del Progetto CUORE. [Evaluation of the global cardiovascular absolute risk: the Progetto CUORE individual score]. Ann Ist Super Sanità 2004;40(4):393-9
  • Ferrario M, Chiodini P, Chambless LE, et al. Assessing accuracy of the CUORE Cohort Study prediction equation. Int J Epidemiol 2005;34(2):413-21
  • CCM. Available from: www.cuore.iss.it/sopra/calc-rischio.asp
  • Bell KJ, Hayen A, Irwig L, et al. When to remeasure cardiovascular risk in untreated people at low and intermediate risk: observational study. BMJ 2013;346:f1895
  • Nasir K, Budoff MJ, Post WS, et al. Electron beam CT versus helical CT scans for assessing coronary calcification: current utility and future directions. Am Heart J 2003;146(6):969-77
  • Musso G, Cassader M, Rosina F, Gambino R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia 2012;55(4):885-904
  • Conlon BA, Beasley JM, Aebersold K, et al. Nutritional management of insulin resistance in nonalcoholic fatty liver disease (NAFLD). Nutrients 2013;5(10):4093-114
  • Czernichow S, Thomas D, Bruckert E. n-6 Fatty acids and cardiovascular health: a review of the evidence for dietary intake recommendations. Br J Nutr 2010;104(6):788-96
  • Cortez-Pinto H, Jesus L, Barros H, et al. How different is the dietary pattern in non-alcoholic steatohepatitis patients? Clin Nutr 2006;25(5):816-23
  • Puri P, Baillie RA, Wiest MM, et al. A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology 2007;46(4):1081-90
  • Bjermo H, Iggman D, Kullberg J, et al. Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. Am J Clin Nutr 2012;95(5):1003-12
  • Estruch R, Ros E, Salas-Salvado J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013;368(14):1279-90
  • Ryan MC, Itsiopoulos C, Thodis T, et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol 2013;59(1):138-43
  • Kontogianni MD, Tileli N, Margariti A, et al. Adherence to the Mediterranean diet is associated with the severity of non-alcoholic fatty liver disease. Clin Nutr 2014;33(4):678-83
  • Bozzetto L, Prinster A, Annuzzi G, et al. Liver fat is reduced by an isoenergetic MUFA diet in a controlled randomized study in type 2 diabetic patients. Diabetes Care 2012;35(7):1429-35
  • Vos MB, Lavine JE. Dietary fructose in nonalcoholic fatty liver disease. Hepatology 2013;57(6):2525-31
  • Carvalhana S, Machado MV, Cortez-Pinto H. Improving dietary patterns in patients with nonalcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care 2012;15(5):468-73
  • Petta S, Marchesini G, Caracausi L, et al. Industrial, not fruit fructose intake is associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients. JHepatol 2013;59(6):1169-76
  • Ross AB, Godin JP, Minehira K, Kirwan JP. Increasing whole grain intake as part of prevention and treatment of nonalcoholic Fatty liver disease. Int J Endocrinol 2013;2013:585876
  • Cho SS, Qi L, Fahey GCJr, Klurfeld DM. Consumption of cereal fiber, mixtures of whole grains and bran, and whole grains and risk reduction in type 2 diabetes, obesity, and cardiovascular disease. Am J Clin Nutr 2013;98(2):594-619
  • Fock KM, Khoo J. Diet and exercise in management of obesity and overweight. J Gastroenterol Hepatol 2013;28(Suppl 4):59-63
  • Dunn W, Xu R, Schwimmer JB. Modest wine drinking and decreased prevalence of suspected nonalcoholic fatty liver disease. Hepatology 2008;47(6):1947-54
  • Moriya A, Iwasaki Y, Ohguchi S, et al. Alcohol consumption appears to protect against non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2011;33(3):378-88
  • Hamabe A, Uto H, Imamura Y, et al. Impact of cigarette smoking on onset of nonalcoholic fatty liver disease over a 10-year period. J Gastroenterol 2011;46(6):769-78
  • Zein CO, Unalp A, Colvin R, Nonalcoholic Steatohepatitis Clinical Research Network. Smoking and severity of hepatic fibrosis in nonalcoholic fatty liver disease. J Hepatol 2011;54(4):753-9
  • Johnson NA, George J. Fitness versus fatness: moving beyond weight loss in nonalcoholic fatty liver disease. Hepatology 2010;52(1):370-81
  • Hallsworth K, Fattakhova G, Hollingsworth KG, et al. Resistance exercise reduces liver fat and its mediators in non-alcoholic fatty liver disease independent of weight loss. Gut 2011;60(9):1278-83
  • Gerber L, Otgonsuren M, Mishra A, et al. Non-alcoholic fatty liver disease (NAFLD) is associated with low level of physical activity: a population-based study. Aliment Pharmacol Ther 2012;36(8):772-81
  • Keating SE, Hackett DA, George J, Johnson NA. Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 2012;57(1):157-66
  • Haus JM, Solomon TP, Kelly KR, et al. Improved hepatic lipid composition following short-term exercise in nonalcoholic fatty liver disease. J Clin Endocrinol Metab 2013;98(7):E1181-8
  • Bacchi E, Negri C, Targher G, et al. Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 randomized trial). Hepatology 2013;58(4):1287-95
  • 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(6):2005-23
  • Thoma C, Day CP, Trenell MI. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol 2012;56(1):255-66
  • Kistler KD, Brunt EM, Clark JM, et al. Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic fatty liver disease. Am J Gastroenterol 2011;106(3):460-8
  • Pinto A, Di Raimondo D, Tuttolomondo A, et al. Effects of physical exercise on inflammatory markers of atherosclerosis. Curr Pharm Des 2012;18(28):4326-49
  • Polyzos SA, Kountouras J, Anastasilakis AD, et al. Irisin in patients with nonalcoholic fatty liver disease. Metabolism 2014;63(2):207-17
  • Kimball SR. Integration of signals generated by nutrients, hormones, and exercise in skeletal muscle. Am J Clin Nutr 2014;99(1):237S-2S
  • Ratziu V. Pharmacological agents for NASH. Nat Rev Gastroenterol Hepatol 2013;10(11):676-85
  • Younossi ZM, Reyes MJ, Mishra A, et al. Systematic review with meta-analysis: non-alcoholic steatohepatitis - a case for personalised treatment based on pathogenic targets. Aliment Pharmacol Ther 2014;39(1):3-14
  • Mazzella N, Ricciardi LM, Mazzotti A, Marchesini G. The role of medications for the management of patients with NAFLD. Clin Liver Dis 2014;18(1):73-89
  • Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010;362(18):1675-85
  • Lonardo A, Bellentani S, Ratziu V, Loria P. Insulin resistance in nonalcoholic steatohepatitis: necessary but not sufficient - death of a dogma from analysis of therapeutic studies? Expert Rev Gastroenterol Hepatol 2011;5(2):279-89
  • Lavine JE, Schwimmer JB, Van Natta ML, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA 2011;305(16):1659-68
  • Bjelakovic G, Nikolova D, Gluud C. Antioxidant supplements to prevent mortality. JAMA 2013;310(11):1178-9
  • Loria P, Lonardo A, Anania F. Liver and diabetes. A vicious circle. Hepatol Res 2013;43(1):51-64
  • Cicero AF, Tartagni E, Ertek S. Metformin and its clinical use: new insights for an old drug in clinical practice. Arch Med Sci 2012;8(5):907-17
  • Wang P, Kang D, Cao W, et al. Diabetes mellitus and risk of hepatocellular carcinoma: a systematic review and meta-analysis. Diabetes Metab Res Rev 2012;28(2):109-22
  • Singh S, Singh PP, Singh AG, et al. Anti-diabetic medications and the risk of hepatocellular cancer: a systematic review and meta-analysis. Am J Gastroenterol 2013;108(6):881-91
  • Zhang H, Gao C, Fang L, et al. Metformin and reduced risk of hepatocellular carcinoma in diabetic patients: a meta-analysis. Scand J Gastroenterol 2013;48(1):78-87
  • Chen HP, Shieh JJ, Chang CC, et al. Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies. Gut 2013;62(4):606-15
  • Bhalla K, Hwang BJ, Dewi RE, et al. Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic lipogenesis. Cancer Prev Res (Phila) 2012;5(4):544-52
  • Lilly M, Godwin M. Treating prediabetes with metformin: systematic review and meta-analysis. Can Fam Physician 2009;55(4):363-9
  • Sofer E, Boaz M, Matas Z, et al. Treatment with insulin sensitizer metformin improves arterial properties, metabolic parameters, and liver function in patients with nonalcoholic fatty liver disease: a randomized, placebo-controlled trial. Metabolism 2011;60(9):1278-84
  • de Jager J, Kooy A, Schalkwijk C, et al. Long-term effects of metformin on endothelial function in type 2 diabetes: a randomized controlled trial. J Intern Med 2014;275(1):59-70
  • Fruci B, Giuliano S, Mazza A, et al. Nonalcoholic fatty liver: a possible new target for type 2 diabetes prevention and treatment. Int J Mol Sci 2013;14(11):22933-66
  • 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(1):66-75
  • Lutchman G, Modi A, Kleiner DE, et al. The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology 2007;46(2):424-9
  • 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. JAMA 2007;298(10):1180-8
  • 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(7):1953-62
  • Hiatt WR, Kaul S, Smith RJ. The cardiovascular safety of diabetes drugs - insights from the rosiglitazone experience. N Engl J Med 2013;369(14):1285-7
  • Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007;132(6):2131-57
  • Wajcberg E, Tavaria A. Exenatide: clinical aspects of the first incretin-mimetic for the treatment of type 2 diabetes mellitus. Expert Opin Pharmacother 2009;10(1):135-42
  • Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 2006;368(9548):1696-705
  • Ding X, Saxena NK, Lin S, et al. Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice. Hepatology 2006;43(1):173-81
  • Trevaskis JL, Griffin PS, Wittmer C, et al. Glucagon-like peptide-1 receptor agonism improves metabolic, biochemical, and histopathological indices of nonalcoholic steatohepatitis in mice. Am J Physiol Gastrointest Liver Physiol 2012;302(8):G762-72
  • Gupta NA, Mells J, Dunham RM, et al. Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway. Hepatology 2010;51(5):1584-92
  • Sharma S, Mells JE, Fu PP, et al. GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing the unfolded protein response and promoting macroautophagy. PLoS One 2011;6(9):e25269
  • Bernsmeier C, Meyer-Gerspach AC, Blaser LS, et al. Glucose-induced glucagon-like Peptide 1 secretion is deficient in patients with non-alcoholic Fatty liver disease. PLoS One 2014;9(1):e87488
  • Klonoff DC, Buse JB, Nielsen LL, et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 2008;24(1):275-86
  • Cuthbertson DJ, Irwin A, Gardner CJ, et al. Improved glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists. PLoS One 2012;7(12):e50117
  • Sathyanarayana P, Jogi M, Muthupillai R, et al. Effects of combined exenatide and pioglitazone therapy on hepatic fat content in type 2 diabetes. Obesity (Silver Spring) 2011;19(12):2310-15
  • Kenny PR, Brady DE, Torres DM, et al. Exenatide in the treatment of diabetic patients with non-alcoholic steatohepatitis: a case series. Am J Gastroenterol 2010;105(12):2707-9
  • Armstrong MJ, Houlihan DD, Rowe IA, et al. Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta-analysis of the LEAD program. Aliment Pharmacol Ther 2013;37(2):234-42
  • Ohki T, Isogawa A, Iwamoto M, et al. The effectiveness of liraglutide in nonalcoholic fatty liver disease patients with type 2 diabetes mellitus compared to sitagliptin and pioglitazone. Sci World J 2012;2012:496453
  • Suzuki D, Toyoda M, Kimura M, et al. Effects of liraglutide, a human glucagon-like peptide-1 analogue, on body weight, body fat area and body fat-related markers in patients with type 2 diabetes mellitus. Intern Med 2013;52(10):1029-34
  • Kahal H, Abouda G, Rigby AS, et al. Glucagon-like peptide-1 analogue, liraglutide, improves liver fibrosis markers in obese women with polycystic ovary syndrome and nonalcoholic fatty liver disease. Clin Endocrinol (Oxf) 2014;81(4):523-8
  • Kern M, Kloting N, Niessen HG, et al. Linagliptin improves insulin sensitivity and hepatic steatosis in diet-induced obesity. PLoS One 2012;7(6):e38744
  • Akaslan SB, Degertekin CK, Yilmaz G, et al. Effects of sitagliptin on nonalcoholic fatty liver disease in diet-induced obese rats. Metab Syndr Relat Disord 2013;11(4):243-50
  • Iwasaki T, Yoneda M, Inamori M, et al. Sitagliptin as a novel treatment agent for non-alcoholic Fatty liver disease patients with type 2 diabetes mellitus. Hepatogastroenterology 2011;58(112):2103-5
  • Yilmaz Y, Yonal O, Deyneli O, et al. Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis. Acta Gastroenterol Belg 2012;75(2):240-4
  • Petrie JR. The cardiovascular safety of incretin-based therapies: a review of the evidence. Cardiovasc Diabetol 2013;12:130
  • Mundil D, Cameron-Vendrig A, Husain M. GLP-1 receptor agonists: a clinical perspective on cardiovascular effects. Diab Vasc Dis Res 2012;9(2):95-108
  • Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369(14):1317-26
  • White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med 2013;369(14):1327-35
  • Lonardo A, Loria P. Potential for statins in the chemoprevention and management of hepatocellular carcinoma. J Gastroenterol Hepatol 2012;27(11):1654-64
  • Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013;1:CD004816
  • Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ 2010;340:c2197
  • Athyros VG, Tziomalos K, Gossios TD, et al. Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis. Lancet 2010;376(9756):1916-22
  • Tikkanen MJ, Fayyad R, Faergeman O, et al. Effect of intensive lipid lowering with atorvastatin on cardiovascular outcomes in coronary heart disease patients with mild-to-moderate baseline elevations in alanine aminotransferase levels. Int J Cardiol 2013;168(4):3846-52
  • Musso G, Gambino R, Cassader M, Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology 2010;52(1):79-104
  • Singh S, Singh PP, Singh AG, et al. Statins are associated with a reduced risk of hepatocellular cancer: a systematic review and meta-analysis. Gastroenterology 2013;144(2):323-32
  • Lai SW, Liao KF, Lai HC, et al. Statin use and risk of hepatocellular carcinoma. Eur J Epidemiol 2013;28(6):485-92
  • Tsan YT, Lee CH, Ho WC, et al. Statins and the risk of hepatocellular carcinoma in patients with hepatitis C virus infection. J Clin Oncol 2013;31(12):1514-21
  • Pradelli D, Soranna D, Scotti L, et al. Statins and primary liver cancer: a meta-analysis of observational studies. Eur J Cancer Prev 2013;22(3):229-34
  • Singh S, Singh PP, Roberts LR, Sanchez W. Chemopreventive strategies in hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2014;11(1):45-54
  • Argo CK, Loria P, Caldwell SH, Lonardo A. Statins in liver disease: a molehill, an iceberg, or neither? Hepatology 2008;48(2):662-9
  • Yoshimoto S, Loo TM, Atarashi K, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 2013;499(7456):97-101
  • Hyogo H, Yamagishi S, Maeda S, et al. Atorvastatin improves disease activity of nonalcoholic steatohepatitis partly through its tumour necrosis factor-α-lowering property. Dig Liver Dis 2012;44(6):492-6
  • Lonardo A, Loria P. If steatosis is the atherosclerosis of the liver, are statins the “aspirin” for steatosis? Dig Liver Dis 2012;44(6):451-2
  • Mills EJ, Wu P, Chong G, et al. Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials. QJM 2011;104(2):109-24
  • Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010;375(9716):735-42
  • Calderon RM, Cubeddu LX, Goldberg RB, Schiff ER. Statins in the treatment of dyslipidemia in the presence of elevated liver aminotransferase levels: a therapeutic dilemma. Mayo Clin Proc 2010;85(4):349-56
  • Younoszai Z, Li Z, Stepanova M, et al. Statin use is not associated with liver related mortality. Ann Hepatol 2014;13(1):84-90
  • Eslami L, Merat S, Malekzadeh R, et al. Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Cochrane Database Syst Rev 2013;12:CD008623
  • Choi HD, Shin WG. Safety and efficacy of statin treatment alone and in combination with fibrates in patients with dyslipidemia: a meta-analysis. Curr Med Res Opin 2014;30(1):1-10
  • Athyros VG, Tziomalos K, Daskalopoulos GN, et al. Statin-based treatment for cardiovascular risk and non-alcoholic fatty liver disease. Killing two birds with one stone? Ann Med 2011;43(3):167-71
  • Catapano AL, Reiner Z, De Backer G, et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis 2011;217(1):3-46
  • Targher G, Byrne CD. Diagnosis and management of nonalcoholic fatty liver disease and its hemostatic/thrombotic and vascular complications. Semin Thromb Hemost 2013;39(2):214-28
  • Kris-Etherton PM, Harris WS, Appel LJ; AHA Nutrition Committee American Heart Association. Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association. Arterioscler Thromb Vasc Biol 2003;23(2):151-2
  • Cussons AJ, Watts GF, Mori TA, Stuckey BGA. Omega-3 fatty acid supplementation decreases liver fat content in polycystic ovary syndrome: a randomized controlled trial employing proton magnetic resonance spectroscopy. J Clin Endocrinol Metab 2009;94(10):3842-8
  • Parker HM, Johnson NA, Burdon CA, et al. Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol 2012;56(4):944-51
  • Shearer GC, Savinova OV, Harris WS. Fish oil — how does it reduce plasma triglycerides? Biochim Biophys Acta 2012;1821(5):843-51
  • Dasarathy S, Dasarathy J, Khiyami A, et al.et al. Double-blind randomized placebo-controlled clinical trial of omega 3 fatty acids for the treatment of diabetic patients with nonalcoholic steatohepatitis. J Clin Gastroenterol 2014. [Epub ahead of print]
  • Marik PE, Varon J. Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clin Cardiol 2009;32(27):365-72
  • Risk and Prevention Study Collaborative Group, Roncaglioni MC, Tombesi M, Avanzini F, et al. n-3 fatty acids in patients with multiple cardiovascular risk factors. N Engl J Med 2013;368(19):1800-8
  • Phan BA, Dayspring TD, Toth PP. Ezetimibe therapy: mechanism of action and clinical update. Vasc Health Risk Manag 2012;8:415-27
  • Van Rooyen DM, Larter CZ, Haigh WG, et al. Hepatic free cholesterol accumulates in obese, diabetic mice and causes nonalcoholic steatohepatitis. Gastroenterology 2011;141(4):1393-403. 1403.e1-5
  • Ballestri S, Day CP, Daly AK. Polymorphism in the farnesyl diphosphate farnesyl transferase 1 gene and nonalcoholic fatty liver disease severity. Gastroenterology 2011;140(5):1694-5
  • Van Rooyen DM, Gan LT, Yeh MM, et al. Pharmacological cholesterol lowering reverses fibrotic NASH in obese, diabetic mice with metabolic syndrome. J Hepatol 2013;59(1):144-52
  • Park H, Shima T, Yamaguchi K, et al. Efficacy of long-term ezetimibe therapy in patients with nonalcoholic fatty liver disease. J Gastroenterol 2011;46(1):101-7
  • Chan DC, Watts GF, Gan SK, et al. Effect of ezetimibe on hepatic fat, inflammatory markers and apolipoprotein B-100 kinetics in insulin-resistant obese subjects on a weight loss diet. Diabetes Care 2010;33(5):1134-9
  • Takeshita Y, Takamura T, Honda M, et al. The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial. Diabetologia 2014;57(5):878-90
  • Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 2010;363(14):1341-50
  • Kalupahana NS, Moustaid-Moussa N. The renin-angiotensin system: a link between obesity, inflammation and insulin resistance. Obes Rev 2012;13(2):136-49
  • Paschos P, Tziomalos K. Nonalcoholic fatty liver disease and the renin-angiotensin system: implications for treatment. World J Hepatol 2012;4(12):327-31
  • Yokohama S, Yoneda M, Haneda M, et al. Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology 2004;40(5):1222-5
  • Kudo H, Yata Y, Takahara T, et al. Telmisartan attenuates progression of steatohepatitis in mice: role of hepatic macrophage infiltration and effects on adipose tissue. Liver Int 2009;29(7):988-96
  • Georgescu EF, Ionescu R, Georgescu M, et al. Angiotensin receptor blockers as therapy for mild-to-moderate hypertension associated non-alcoholic steatohepatitis. World J Gastroenterol 2009;15(8):942-54
  • Fogari R, Maffioli P, Mugellini A, et al. Effects of losartan and amlodipine alone or combined with simvastatin in hypertensive patients with nonalcoholic hepatic steatosis. Eur J Gastroenterol Hepatol 2012;24(2):164-71
  • Hirata T, Tomita K, Kawai T, et al. Effect of telmisartan or losartan for treatment of nonalcoholic fatty liver disease: fatty liver protection trial by telmisartan or losartan study (FANTASY). Int J Endocrinol 2013;2013:587140
  • Tamaki Y, Nakade Y, Yamauchi T, et al. Angiotensin II type 1 receptor antagonist prevents hepatic carcinoma in rats with nonalcoholic steatohepatitis. J Gastroenterol 2013;48(4):491-503
  • Andraws R, Brown DL. Effect of inhibition of the renin-angiotensin system on development of type 2 diabetes mellitus (meta-analysis of randomized trials). Am J Cardiol 2007;99(7):1006-12
  • Imaz I, Martínez-Cervell C, García-Alvarez EE, et al. Safety and effectiveness of the intragastric balloon for obesity. A meta-analysis. Obes Surg 2008;18(7):841-6
  • Genco A, López-Nava G, Wahlen C, et al. Multi-centre European experience with intragastric balloon in overweight populations: 13 years of experience. Obes Surg 2013;23(4):515-21
  • Kotzampassi K, Grosomanidis V, Papakostas P, et al. 500 intragastric balloons: what happens 5 years thereafter? Obes Surg 2012;22(6):896-903
  • Dogan UB, Gumurdulu Y, Akin MS, Yalaki S. Five percent weight lost in the first month of intragastric balloon treatment may be a predictor for long-term weight maintenance. Obes Surg 2013;23(7):892-6
  • Farina MG, Baratta R, Nigro A, et al. Intragastric balloon in association with lifestyle and/or pharmacotherapy in the long-term management of obesity. Obes Surg 2012;22(4):565-71
  • Lee YM, Low HC, Lim LG, et al. Intragastric balloon significantly improves nonalcoholic fatty liver disease activity score in obese patients with nonalcoholic steatohepatitis: a pilot study. Gastrointest Endosc 2012;76(4):756-60
  • Hafeez S, Ahmed MH. Bariatric surgery as potential treatment for nonalcoholic fatty liver disease: a future treatment by choice or by chance? J Obes 2013;2013:839275
  • Mummadi RR, Kasturi KS, Chennareddygari S, Sood GK. Effect of bariatric surgery on nonalcoholic fatty liver disease: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2008;6(12):1396-402
  • Vest AR, Heneghan HM, Agarwal S, et al. Bariatric surgery and cardiovascular outcomes: a systematic review. Heart 2012;98(24):1763-77
  • Carlsson LM, Peltonen M, Ahlin S, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med 2012;367(8):695-704
  • Sjöström L, Peltonen M, Jacobson P, et al. Bariatric surgery and long-term cardiovascular events. JAMA 2012;307(1):56-65
  • Dekker JM, Girman C, Rhodes T, et al. Metabolic syndrome and 10-year cardiovascular disease risk in the Hoorn Study. Circulation 2005;112(5):666-73
  • Goff DCJr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(25 Suppl 2):S49-73
  • Visser ME, Wagener G, Baker BF, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial. Eur Heart J 2012;33(9):1142-9
  • Sjouke B, Balak DM, Beuers U, et al. Is mipomersen ready for clinical implementation? A transatlantic dilemma. Curr Opin Lipidol 2013;24(4):301-6
  • Stefan N, Ramsauer M, Jordan P, et al. Inhibition of 11β-HSD1 with RO5093151 for non-alcoholic fatty liver disease: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 2014;2(5):406-16
  • Loria P, Carulli L, Bertolotti M, Lonardo A. Endocrine and liver interaction: the role of endocrine pathways in NASH. Nat Rev Gastroenterol Hepatol 2009;6(4):236-47
  • Targher G, Scorletti E, Mantovani A, Byrne CD. Nonalcoholic fatty liver disease and reduced serum vitamin D3 levels. Metab Syndr Relat Disord 2013;11(4):217-28
  • Scorletti E, Byrne CD. Omega-3 fatty acids, hepatic lipid metabolism, and nonalcoholic fatty liver disease. Annu Rev Nutr 2013;33:231-48

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