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NAFLD and Cardiovascular Disease: Can the Real Association Be Determined?

  • Fatty Liver Disease (SA Harrison and J George, Section Editors)
  • Published:
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Abstract

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of liver diseases ranging from isolated hepatic steatosis (IHS) to non-alcoholic steatohepatitis (NASH) defined by the presence of hepatocellular injury, and may progress to end-stage liver disease and its complications. Mounting evidence also suggests that direct effects on the heart may explain why cardiovascular disease (CVD), comprising coronary artery disease and cerebrovascular disease, is the leading cause of death among individuals with NASH. CVD and NASH share common risk factors, however NASH may increase atherogenic risk or alter cardiac function independent of these commonalities. A complex interplay between an inflamed visceral fat compartment, the liver and the endothelium creates a pro-inflammatory, pro-coagulant and pro-atherogenic milieu that can contribute to accelerated atherosclerosis and cardiac dysfunction. While new evidence is accumulating that might help close the gap in our understanding of the putative role of NASH in CVD, more prospective data are still needed.

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Abbreviations

ALT:

Alanine transaminase

ApoB:

Apolipoprotein B

ACE:

Angiotensin converting enzyme

CF2:

Chorion factor 2

CAC:

Coronary artery calcium

CIMT:

Carotid intima-media thickness

CVD:

Cardiovascular disease

FamHS:

Family Heart Study

FMD:

Flow-mediated dilation

GGT:

Gamma glutamyl transpeptidase

HTN:

Hypertension

HDL:

High density lipoprotein

HDL-c:

High density lipoprotein cholesterol

IHS:

Isolated hepatic steatosis

IL3:

Interleukin 1A (IL1A) Interleukin 3

IL-6:

Interleukin-1β(IL-1β) Interleukin-6

LDL-c:

Low density lipoprotein cholesterol

LDL-p:

Low density lipoprotein particles

LT:

Liver transplantation

MetS:

Metabolic syndrome

MCP-1:

Monocyte chemotactic protein-1

NHANESIII:

National Health and Nutrition Examination Survey

NAFLD:

Non-alcoholic fatty liver disease

NASH:

Non-alcoholic steatohepatitis

NFS:

NAFLD fibrosis score

NO:

Nitric Oxide

eNOS:

Nitric oxide synthetase

oxLDL:

Oxidized low density lipoprotein

PAT:

Pperipheral arterial tone

PAI-1:

Plasminogen activator inhibitor-1

RCRI:

Revised Cardiac Risk Index

sdLDL:

Small dense low density lipoprotein

TGFβ1:

Transforming growth factor beta 1

TMAO:

Trimethylamine N-oxide

TNF-α:

Tumor necrosis factor-α

T2DM:

Type-2 diabetes mellitus

VLDL:

Very low density lipoprotein

v-WF:

von Willebrand factor

VAT:

Visceral adipose tissue

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Younossi ZM, Stepanova M, Afendy M, Fang Y, Younossi Y, Mir H, 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 Off Clin Pract J Am Gastroenterol Assoc. 2011;9(6):524–30 e1. quiz e60. PubMed PMID: 21440669.

    Google Scholar 

  2. Williams CD, Stengel J, Asike MI, Torres DM, Shaw J, Contreras M, 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. PubMed PMID: 20858492.

    PubMed  Google Scholar 

  3. Armstrong MJ, Houlihan DD, Bentham L, Shaw JC, Cramb R, Olliff S, et al. Presence and severity of non-alcoholic fatty liver disease in a large prospective primary care cohort. J Hep. 2012;56(1):234–40. PubMed PMID: 21703178.

    Google Scholar 

  4. Vega GL, Chandalia M, Szczepaniak LS, Grundy SM. Metabolic correlates of nonalcoholic fatty liver in women and men. Hepatology. 2007;46(3):716–22. PubMed PMID: 17659597.

    CAS  PubMed  Google Scholar 

  5. Park BJ, Kim YJ, Kim DH, Kim W, Jung YJ, Yoon JH, et al. Visceral adipose tissue area is an independent risk factor for hepatic steatosis. J Gastroenterol Hepatol. 2008;23(6):900–7. PubMed PMID: 17995942.

    CAS  PubMed  Google Scholar 

  6. Kotronen A, Juurinen L, Tiikkainen M, Vehkavaara S, Yki-Jarvinen H. Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. Gastroenterology. 2008;135(1):122–30. PubMed PMID: 18474251.

    CAS  PubMed  Google Scholar 

  7. White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2012;10(12):1342–59 e2. PubMed PMID: 23041539. Pubmed Central PMCID: 3501546.

    Google Scholar 

  8. Argo CK, Northup PG, Al-Osaimi AM, Caldwell SH. Systematic review of risk factors for fibrosis progression in non-alcoholic steatohepatitis. J hepatol. 2009;51(2):371–9. PubMed PMID: 19501928.

    CAS  PubMed  Google Scholar 

  9. Pais R, Charlotte F, Fedchuk L, Bedossa P, Lebray P, Poynard T, 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. PubMed PMID: 23665288.

    CAS  PubMed  Google Scholar 

  10. Kemmer N, Neff GW, Franco E, Osman-Mohammed H, Leone J, Parkinson E, et al. Nonalcoholic fatty liver disease epidemic and its implications for liver transplantation. Transplantation. 2013;96(10):860–2. PubMed PMID: 24247899.

    CAS  PubMed  Google Scholar 

  11. Baumeister SE, Volzke H, Marschall P, John U, Schmidt CO, Flessa S, et al. Impact of fatty liver disease on health care utilization and costs in a general population: a 5-year observation. Gastroenterology. 2008;134(1):85–94. PubMed PMID: 18005961.

    PubMed  Google Scholar 

  12. 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(1):113–21. PubMed PMID: 16012941.

    PubMed  Google Scholar 

  13. 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(4):865–73. PubMed PMID: 17006923.

    CAS  PubMed  Google Scholar 

  14. Expert Panel on Detection E, Treatment of High Blood Cholesterol in A. Executive Summary of The 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). J Am Med Assoc. 2001;285(19):2486–97. PubMed PMID: 11368702.

    Google Scholar 

  15. Alberti KG, Zimmet P, Shaw J. Metabolic syndrome–a new world-wide definition. A Consensus statement from the international diabetes federation. Diabet Med J Br Diabet Assoc. 2006;23(5):469–80. PubMed PMID: 16681555.

    CAS  Google Scholar 

  16. 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(10):722–8. PubMed PMID: 16287793.

    CAS  PubMed  Google Scholar 

  17. Yamada J, Tomiyama H, Yambe M, Koji Y, Motobe K, Shiina K, et al. Elevated serum levels of alanine aminotransferase and gamma glutamyltransferase are markers of inflammation and oxidative stress independent of the metabolic syndrome. Atherosclerosis. 2006;189(1):198–205. PubMed PMID: 16405892.

    CAS  PubMed  Google Scholar 

  18. Schindhelm RK, Dekker JM, Nijpels G, Bouter LM, Stehouwer CD, Heine RJ, et al. Alanine aminotransferase predicts coronary heart disease events: a 10-year follow-up of the Hoorn Study. Atherosclerosis. 2007;191(2):391–6. PubMed PMID: 16682043.

    CAS  PubMed  Google Scholar 

  19. Kunde SS, Lazenby AJ, Clements RH, Abrams GA. Spectrum of NAFLD and diagnostic implications of the proposed new normal range for serum ALT in obese women. Hepatology. 2005;42(3):650–6. PubMed PMID: 16037946.

    PubMed  Google Scholar 

  20. 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(6):1286–92. PubMed PMID: 12774006.

    PubMed  Google Scholar 

  21. Cazzo E, de Felice Gallo F, Pareja JC, Chaim EA. Nonalcoholic Fatty Liver Disease in Morbidly Obese Subjects: Correlation Among Histopathologic Findings, Biochemical Features, and Ultrasound Evaluation. Obes Surg. 2014. doi:10.1007/s11695-014-1183-4

  22. Mishra P, Younossi ZM. Abdominal ultrasound for diagnosis of nonalcoholic fatty liver disease (NAFLD). Am J Gastroenterol. 2007;102(12):2716–7. PubMed PMID: 18042105.

    PubMed  Google Scholar 

  23. Awai HI, Newton KP, Sirlin CB, Behling C, Schwimmer JB. Evidence and Recommendations for Imaging Liver Fat in Children, Based on Systematic Review. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2013. doi:10.1016/j.cgh.2013.09.050. PubMed PMID: 24090729.

    Google Scholar 

  24. Ong JP, Pitts A, Younossi ZM. Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol. 2008;49(4):608–12. PubMed PMID: 18682312. eng.

    PubMed  Google Scholar 

  25. Dunn W, Xu R, Wingard DL, Rogers C, Angulo P, Younossi ZM, et al. Suspected nonalcoholic fatty liver disease and mortality risk in a population-based cohort study. Am J Gastroenterol. 2008;103(9):2263–71. PubMed PMID: 18684196 Pubmed Central PMCID: 2574666.

    PubMed Central  PubMed  Google Scholar 

  26. Soderberg C, Stal P, Askling J, Glaumann H, Lindberg G, Marmur J, et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology. 2010;51(2):595–602. PubMed PMID: 20014114.

    PubMed  Google Scholar 

  27. Calori G, Lattuada G, Ragogna F, Garancini MP, Crosignani P, Villa M, et al. Fatty liver index and mortality: the Cremona study in the 15th year of follow-up. Hepatology. 2011;54(1):145–52. PubMed PMID: 21488080.

    CAS  PubMed  Google Scholar 

  28. Stepanova M, Rafiq N, Makhlouf H, Agrawal R, Kaur I, Younoszai Z, et al. Predictors of all-cause mortality and liver-related mortality in patients with non-alcoholic fatty liver disease (NAFLD). Dig Dis Sci. 2013;58(10):3017–23. PubMed PMID: 23775317.

    CAS  PubMed  Google Scholar 

  29. Angulo P, Bugianesi E, Bjornsson ES, Charatcharoenwitthaya P, Mills PR, Barrera F, et al. Simple noninvasive systems predict long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2013;145(4):782–9 e4. PubMed PMID: 23860502.

    PubMed  Google Scholar 

  30. Lazo M, Hernaez R, Bonekamp S, Kamel IR, Brancati FL, Guallar E, et al. Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study. Bmj. 2011;343:d6891. PubMed PMID: 22102439 Pubmed Central PMCID: 3220620.

    PubMed Central  PubMed  Google Scholar 

  31. Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846–54. PubMed PMID: 17393509. eng.

    CAS  PubMed  Google Scholar 

  32. Kim D, Kim WR, Kim HJ, Therneau TM. Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology. 2013;57(4):1357–65. PubMed PMID: 23175136 Pubmed Central PMCID: 3622816.

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Rafiq N, Bai C, Fang Y, Srishord M, McCullough A, Gramlich T, et al. Long-term follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2009;7(2):234–8. PubMed PMID: 19049831.

    Google Scholar 

  34. Dam-Larsen S, Becker U, Franzmann MB, Larsen K, Christoffersen P, Bendtsen F. Final results of a long-term, clinical follow-up in fatty liver patients. Scand J Gastroenterol. 2009;44(10):1236–43. PubMed PMID: 19670076.

    CAS  PubMed  Google Scholar 

  35. Therapondos G, Flapan AD, Plevris JN, Hayes PC. Cardiac morbidity and mortality related to orthotopic liver transplantation. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2004;10(12):1441–53. PubMed PMID: 15558590.

    Google Scholar 

  36. Watt KD, Pedersen RA, Kremers WK, Heimbach JK, Charlton MR. Evolution of causes and risk factors for mortality post-liver transplant: results of the NIDDK long-term follow-up study. Am J Transplant Offi J Am Soc Transplant Am Soc Transplant Surg. 2010;10(6):1420–7. PubMed PMID: 20486907 Pubmed Central PMCID: 2891375.

    CAS  Google Scholar 

  37. Gonwa TA. Hypertension and renal dysfunction in long-term liver transplant recipients. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2001;7(11 Suppl 1):S22–6. PubMed PMID: 11689773.

    CAS  Google Scholar 

  38. Wiese S, Hove JD, Bendtsen F, Møller S. Cirrhotic cardiomyopathy: pathogenesis and clinical relevance. Nat Rev Gastroenterol Hepatol. 2014;11(3):177–86.

    Google Scholar 

  39. Darstein F, König C, Hoppe-Lotichius M, Grimm D, Knapstein J, Mittler J, et al. Preoperative left ventricular hypertrophy is associated with reduced patient survival after liver transplantation. Clin Transplant. 2014;28(2):236–42.

    Google Scholar 

  40. Albeldawi M, Aggarwal A, Madhwal S, Cywinski J, Lopez R, Eghtesad B, et al. Cumulative risk of cardiovascular events after orthotopic liver transplantation. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2012;18(3):370–5. PubMed PMID: 22140067.

    Google Scholar 

  41. Vanwagner LB, Bhave M, Te HS, Feinglass J, Alvarez L, Rinella ME. Patients transplanted for nonalcoholic steatohepatitis are at increased risk for postoperative cardiovascular events. Hepatology. 2012;56(5):1741–50. A retrospective cohort study of 242 patients who underwent LT for NASH or alcohol-related liver disease demonstrated that NASH patients were more likely to have adverse CV events in the first year post-transplant compared to those with alcohol-related liver disease even after controlling for pre-transplant risk-factors such as MetS, CV disease or T2DM.

    PubMed  Google Scholar 

  42. Lee TH. Reducing cardiac risk in noncardiac surgery. New Engl J Med. 1999;341(24):1838–40. PubMed PMID: 10588971.

    CAS  PubMed  Google Scholar 

  43. Wang X, Li J, Riaz DR, Shi G, Liu C, Dai Y. Outcomes of Liver Transplantation for Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2013. doi:10.1016/j.cgh.2013.09.023. A meta-analysis of 9 studies comparing post-LT outcomes among patients who underwent LT for NASH cirrhosis vs. other etiologies. Higher risk of post-transplant death from CV outcomes among NASH patients.

    Google Scholar 

  44. Kadayifci A, Tan V, Ursell PC, Merriman RB, Bass NM. Clinical and pathologic risk factors for atherosclerosis in cirrhosis: a comparison between NASH-related cirrhosis and cirrhosis due to other aetiologies. J Hepatol. 2008;49(4):595–9. PubMed PMID: 18662837.

    PubMed  Google Scholar 

  45. Stepanova M, Younossi ZM. Independent association between nonalcoholic fatty liver disease and cardiovascular disease in the US population. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2012;10(6):646–50. PubMed PMID: 22245962.

    Google Scholar 

  46. Ford ES, Giles WH, Mokdad AH. The distribution of 10-Year risk for coronary heart disease among US adults: findings from the National Health and Nutrition Examination Survey III. J Am Coll Cardiol. 2004;43(10):1791–6. PubMed PMID: 15145101.

    PubMed  Google Scholar 

  47. Treeprasertsuk S, Leverage S, Adams LA, Lindor KD, St Sauver J, Angulo P. The Framingham risk score and heart disease in nonalcoholic fatty liver disease. Liver Int Off J Int Assoc Study Liver. 2012;32(6):945–50. PubMed PMID: 22299674 Pubmed Central PMCID: 3348257.

    Google Scholar 

  48. Dekker JM, Girman C, Rhodes T, Nijpels G, Stehouwer CD, Bouter LM, et al. Metabolic syndrome and 10-year cardiovascular disease risk in the Hoorn Study. Circulation. 2005;112(5):666–73. PubMed PMID: 16061755.

    PubMed  Google Scholar 

  49. Yun KE, Shin CY, Yoon YS, Park HS. Elevated alanine aminotransferase levels predict mortality from cardiovascular disease and diabetes in Koreans. Atherosclerosis. 2009;205(2):533–7. PubMed PMID: 19159884.

    CAS  PubMed  Google Scholar 

  50. Targher G, Marra F, Marchesini G. Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon? Diabetologia. 2008;51(11):1947–53. PubMed PMID: 18762907.

    CAS  PubMed  Google Scholar 

  51. Ruttmann E, Brant LJ, Concin H, Diem G, Rapp K, Ulmer H, et al. Gamma-glutamyltransferase as a risk factor for cardiovascular disease mortality: an epidemiological investigation in a cohort of 163,944 Austrian adults. Circulation. 2005;112(14):2130–7. PubMed PMID: 16186419.

    CAS  PubMed  Google Scholar 

  52. Lee DH, Silventoinen K, Hu G, Jacobs Jr DR, Jousilahti P, Sundvall J, et al. Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28,838 middle-aged men and women. Eur Heart J. 2006;27(18):2170–6. PubMed PMID: 16772340.

    CAS  PubMed  Google Scholar 

  53. Ruhl CE, Everhart JE. Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population. Gastroenterology. 2009;136(2):477–85 e11. PubMed PMID: 19100265.

    CAS  PubMed  Google Scholar 

  54. Fraser A, Harris R, Sattar N, Ebrahim S, Smith GD, Lawlor DA. Gamma-glutamyltransferase is associated with incident vascular events independently of alcohol intake: analysis of the British Women's Heart and Health Study and Meta-Analysis. Arterioscler Thromb Vasc Biol. 2007;27(12):2729–35. PubMed PMID: 17932318.

    CAS  PubMed  Google Scholar 

  55. Pompella A, Emdin M, Passino C, Paolicchi A. The significance of serum gamma-glutamyltransferase in cardiovascular diseases. Clin Chem Lab Med CCLM / FESCC. 2004;42(10):1085–91. PubMed PMID: 15552264.

    CAS  Google Scholar 

  56. Feitosa MF, Reiner AP, Wojczynski MK, Graff M, North KE, Carr JJ, et al. Sex-influenced association of nonalcoholic fatty liver disease with coronary heart disease. Atherosclerosis. 2013;227(2):420–4. PubMed PMID: 23390892. Pubmed Central PMCID: 3602396.

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Sonoda M, Yonekura K, Yokoyama I, Takenaka K, Nagai R, Aoyagi T. Common carotid intima-media thickness is correlated with myocardial flow reserve in patients with coronary artery disease: a useful non-invasive indicator of coronary atherosclerosis. Int J Cardiol. 2004;93(2–3):131–6. PubMed PMID: 14975538.

    PubMed  Google Scholar 

  58. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation. 2007;115(4):459–67. PubMed PMID: 17242284.

    PubMed  Google Scholar 

  59. Targher G, Bertolini L, Padovani R, Zenari L, Zoppini G, Falezza G. Relation of nonalcoholic hepatic steatosis to early carotid atherosclerosis in healthy men: role of visceral fat accumulation. Diabetes Care. 2004;27(10):2498–500. PubMed PMID: 15451925.

    PubMed  Google Scholar 

  60. Brea A, Mosquera D, Martin E, Arizti A, Cordero JL, Ros E. Nonalcoholic fatty liver disease is associated with carotid atherosclerosis: a case–control study. Arterioscler Thromb Vasc Biol. 2005;25(5):1045–50. PubMed PMID: 15731489.

    CAS  PubMed  Google Scholar 

  61. Volzke H, Robinson DM, Kleine V, Deutscher R, Hoffmann W, Ludemann J, et al. Hepatic steatosis is associated with an increased risk of carotid atherosclerosis. World J Gastroenterol WJG. 2005;11(12):1848–53. PubMed PMID: 15793879.

    Google Scholar 

  62. Fracanzani AL, Burdick L, Raselli S, Pedotti P, Grigore L, Santorelli G, et al. Carotid artery intima-media thickness in nonalcoholic fatty liver disease. Am J Med. 2008;121(1):72–8. PubMed PMID: 18187076.

    PubMed  Google Scholar 

  63. Kim HC, Kim DJ, Huh KB. Association between nonalcoholic fatty liver disease and carotid intima-media thickness according to the presence of metabolic syndrome. Atherosclerosis. 2009;204(2):521–5. PubMed PMID: 18947828.

    CAS  PubMed  Google Scholar 

  64. Caserta CA, Pendino GM, Amante A, Vacalebre C, Fiorillo MT, Surace P, et al. Cardiovascular risk factors, nonalcoholic fatty liver disease, and carotid artery intima-media thickness in an adolescent population in southern Italy. Am J Epidemiol. 2010;171(11):1195–202. PubMed PMID: 20457571.

    PubMed  Google Scholar 

  65. Gastaldelli A, Kozakova M, Hojlund K, Flyvbjerg A, Favuzzi A, Mitrakou A, et al. Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population. Hepatology. 2009;49(5):1537–44. PubMed PMID: 19291789.

    CAS  PubMed  Google Scholar 

  66. Aygun C, Kocaman O, Sahin T, Uraz S, Eminler AT, Celebi A, et al. Evaluation of metabolic syndrome frequency and carotid artery intima-media thickness as risk factors for atherosclerosis in patients with nonalcoholic fatty liver disease. Dig Dis Sci. 2008;53(5):1352–7. PubMed PMID: 17939039.

    PubMed  Google Scholar 

  67. Kozakova M, Palombo C, Eng MP, Dekker J, Flyvbjerg A, Mitrakou A, et al. Fatty liver index, gamma-glutamyltransferase, and early carotid plaques. Hepatology. 2012;55(5):1406–15. PubMed PMID: 22334565.

    CAS  PubMed  Google Scholar 

  68. Sookoian S, Pirola CJ. Non-alcoholic fatty liver disease is strongly associated with carotid atherosclerosis: a systematic review. J Hepatol. 2008;49(4):600–7. PubMed PMID: 18672311.

    PubMed  Google Scholar 

  69. 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(6):1325–30. PubMed PMID: 16732016. eng.

    PubMed  Google Scholar 

  70. Assy N, Djibre A, Farah R, Grosovski M, Marmor A. Presence of coronary plaques in patients with nonalcoholic fatty liver disease. Radiology. 2010;254(2):393–400. PubMed PMID: 20093511.

    PubMed  Google Scholar 

  71. Budoff MJ, Shaw LJ, Liu ST, Weinstein SR, Mosler TP, Tseng PH, et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol. 2007;49(18):1860–70. PubMed PMID: 17481445.

    PubMed  Google Scholar 

  72. Yeboah J, McClelland RL, Polonsky TS, Burke GL, Sibley CT, O'Leary D, et al. Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. J Am Med Assoc. 2012;308(8):788–95. PubMed PMID: 22910756.

    CAS  Google Scholar 

  73. Chen CH, Nien CK, Yang CC, Yeh YH. Association between nonalcoholic fatty liver disease and coronary artery calcification. Dig Dis Sci. 2010;55(6):1752–60. PubMed PMID: 19688595.

    PubMed  Google Scholar 

  74. Liu J, Musani SK, Bidulescu A, Carr JJ, Wilson JG, Taylor HA, et al. Fatty liver, abdominal adipose tissue and atherosclerotic calcification in African Americans: the Jackson Heart Study. Atherosclerosis. 2012;224(2):521–5. PubMed PMID: 22902209 Pubmed Central PMCID: 3459068.

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Sung KC, Wild SH, Kwag HJ, Byrne CD. Fatty liver, insulin resistance, and features of metabolic syndrome: relationships with coronary artery calcium in 10,153 people. Diabetes Care. 2012;35(11):2359–64. PubMed PMID: 22829522 Pubmed Central PMCID: 3476919.

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Santos RD, Nasir K, Conceicao RD, Sarwar A, Carvalho JA, Blumenthal RS. Hepatic steatosis is associated with a greater prevalence of coronary artery calcification in asymptomatic men. Atherosclerosis. 2007;194(2):517–9. PubMed PMID: 17335826.

    CAS  PubMed  Google Scholar 

  77. Jung DH, Lee YJ, Ahn HY, Shim JY, Lee HR. Relationship of hepatic steatosis and alanine aminotransferase with coronary calcification. Clin Chem Lab Med CCLM / FESCC. 2010;48(12):1829–34. PubMed PMID: 20961204.

    CAS  Google Scholar 

  78. Akabame S, Hamaguchi M, Tomiyasu K, Tanaka M, Kobayashi-Takenaka Y, Nakano K, et al. Evaluation of vulnerable coronary plaques and non-alcoholic fatty liver disease (NAFLD) by 64-detector multislice computed tomography (MSCT). Circ J Off J Jpn Circ Soc. 2008;72(4):618–25. PubMed PMID: 18362435.

    Google Scholar 

  79. Petit JM, Guiu B, Terriat B, Loffroy R, Robin I, Petit V, et al. Nonalcoholic fatty liver is not associated with carotid intima-media thickness in type 2 diabetic patients. J Clin Endocrinol Metab. 2009;94(10):4103–6. PubMed PMID: 19584186.

    CAS  PubMed  Google Scholar 

  80. McKimmie RL, Daniel KR, Carr JJ, Bowden DW, Freedman BI, Register TC, et al. Hepatic steatosis and subclinical cardiovascular disease in a cohort enriched for type 2 diabetes: the Diabetes Heart Study. Am J Gastroenterol. 2008;103(12):3029–35. PubMed PMID: 18853970 Pubmed Central PMCID: 3638961.

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Yilmaz Y, Kurt R, Yonal O, Polat N, Celikel CA, Gurdal A, et al. Coronary flow reserve is impaired in patients with nonalcoholic fatty liver disease: association with liver fibrosis. Atherosclerosis. 2010;211(1):182–6. PubMed PMID: 20181335.

    CAS  PubMed  Google Scholar 

  82. Chhabra R, O'Keefe JH, Patil H, O'Keefe E, Thompson RC, Ansari S, et al. Association of coronary artery calcification with hepatic steatosis in asymptomatic individuals. Mayo Clin Proc Mayo Clin. 2013;88(11):1259–65. A recent cross-sectional study of 377 asymptomatic patients that used coronary artery calcium score to show that NAFLD was an independent predictor of significant CAD even to a greater extent than traditional CVD risk factors such as FRS, T2DM and MetS.

  83. Sung KC, Lim YH, Park S, Kang SM, Park JB, Kim BJ, et al. Arterial stiffness, fatty liver and the presence of coronary artery calcium in a large population cohort. Cardiovasc Diabetol. 2013;12(1):162. PubMed PMID: 24191863. Pubmed Central PMCID: 3826844.

    PubMed Central  PubMed  Google Scholar 

  84. Illan-Gomez F, Gonzalvez-Ortega M, Orea-Soler I, Alcaraz-Tafalla MS, Aragon-Alonso A, Pascual-Diaz M, et al. Obesity and inflammation: change in adiponectin, C-reactive protein, tumour necrosis factor-alpha and interleukin-6 after bariatric surgery. Obes Surg. 2012;22(6):950–5. PubMed PMID: 22527592.

    PubMed  Google Scholar 

  85. Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med. 2005;11(2):183–90. PubMed PMID: 15685173 Pubmed Central PMCID: 1440292.

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Bell H, Odegaard OR, Andersson T, Raknerud N. Protein C in patients with alcoholic cirrhosis and other liver diseases. J Hepatol. 1992;14(2–3):163–7. PubMed PMID: 1500680.

    CAS  PubMed  Google Scholar 

  87. Thuy S, Ladurner R, Volynets V, Wagner S, Strahl S, Konigsrainer A, et al. Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake. J Nutr. 2008;138(8):1452–5. PubMed PMID: 18641190.

    CAS  PubMed  Google Scholar 

  88. Sookoian S, Gianotti TF, Rosselli MS, Burgueno AL, Castano GO, Pirola CJ. Liver transcriptional profile of atherosclerosis-related genes in human nonalcoholic fatty liver disease. Atherosclerosis. 2011;218(2):378–85. PubMed PMID: 21664615.

    CAS  PubMed  Google Scholar 

  89. Gaziano JM, Hennekens CH, O'Donnell CJ, Breslow JL, Buring JE. Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation. 1997;96(8):2520–5. PubMed PMID: 9355888.

    CAS  PubMed  Google Scholar 

  90. Cromwell WC, Otvos JD, Keyes MJ, Pencina MJ, Sullivan L, Vasan RS, et al. LDL Particle Number and Risk of Future Cardiovascular Disease in the Framingham Offspring Study - Implications for LDL Management. J Clin Lipidol. 2007;1(6):583–92. PubMed PMID: 19657464 Pubmed Central PMCID: 2720529.

    PubMed Central  PubMed  Google Scholar 

  91. Mora S, Szklo M, Otvos JD, Greenland P, Psaty BM, Goff Jr DC, et al. LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2007;192(1):211–7. PubMed PMID: 16765964.

    CAS  PubMed  Google Scholar 

  92. National Cholesterol Education Program Expert Panel on Detection E, Treatment of High Blood Cholesterol in A. 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. Circulation. 2002;106(25):3143–421. PubMed PMID: 12485966.

    Google Scholar 

  93. Gomez M, Vila J, Elosua R, Molina L, Bruguera J, Sala J, et al. Relationship of lipid oxidation with subclinical atherosclerosis and 10-year coronary events in general population. Atherosclerosis. 2014;232(1):134–40. PubMed PMID: 24401227.

    CAS  PubMed  Google Scholar 

  94. Musso G, Cassader M, De Michieli F, Rosina F, Orlandi F, Gambino R. Nonalcoholic steatohepatitis versus steatosis: adipose tissue insulin resistance and dysfunctional response to fat ingestion predict liver injury and altered glucose and lipoprotein metabolism. Hepatology. 2012;56(3):933–42. Non-obese, non-diabetic, normolipidemic NAFLD patients were subjected to post-prandial lipoprotein profile analysis after an oral fat load and compared to matched-controls. This study demonstrated that patients with NASH not only had a more atherogenic lipid profile, they also had increased adipose tissue dysfunction, inflammation, oxidative stress, cell cycle dysregulation, liver injury, systemic endothelial dysfunction, and early atherosclerosis compared to patients with isolated hepatic steatosis.

    CAS  PubMed  Google Scholar 

  95. DeFilippis AP, Blaha MJ, Martin SS, Reed RM, Jones SR, Nasir K, et al. Nonalcoholic fatty liver disease and serum lipoproteins: the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2013;227(2):429–36. Large prospective cohort study. NAFLD independently associated with atherogenic lipid profile (higher fasting triglycerides, lower HDL levels, higher LDL particle concentration and smaller LDL particle size), which severity of lipid derangement corresponding to severity of NAFLD.

    CAS  PubMed  Google Scholar 

  96. Siddiqui MS, Sterling RK, Luketic VA, Puri P, Stravitz RT, Bouneva I, et al. Association between high-normal levels of alanine aminotransferase and risk factors for atherogenesis. Gastroenterology. 2013;145(6):1271–9 e3. PubMed PMID: 23973920. Pubmed Central PMCID: 3840068.

    CAS  PubMed  Google Scholar 

  97. Villanova N, Moscatiello S, Ramilli S, Bugianesi E, Magalotti D, Vanni E, et al. Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. Hepatology. 2005;42(2):473–80. PubMed PMID: 15981216. eng.

    PubMed  Google Scholar 

  98. Laufs U, Liao JK. Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem. 1998;273(37):24266–71. PubMed PMID: 9727051.

    CAS  PubMed  Google Scholar 

  99. Landmesser U, Bahlmann F, Mueller M, Spiekermann S, Kirchhoff N, Schulz S, et al. Simvastatin versus ezetimibe: pleiotropic and lipid-lowering effects on endothelial function in humans. Circulation. 2005;111(18):2356–63. PubMed PMID: 15867181.

    CAS  PubMed  Google Scholar 

  100. Colak Y, Senates E, Yesil A, Yilmaz Y, Ozturk O, Doganay L, et al. Assessment of endothelial function in patients with nonalcoholic fatty liver disease. Endocrine. 2013;43(1):100–7. PubMed PMID: 22661277.

    CAS  PubMed  Google Scholar 

  101. Aron-Wisnewsky J, Minville C, Tordjman J, Levy P, Bouillot JL, Basdevant A, et al. Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese. J Hepatol. 2012;56(1):225–33. PubMed PMID: 21703181.

    CAS  PubMed  Google Scholar 

  102. Minville C, Hilleret MN, Tamisier R, Aron-Wisnewsky J, Clement K, Trocme C, et al. Nonalcoholic fatty liver disease, nocturnal hypoxia and endothelial function in sleep apnea patients. Chest. 2013. doi:10.1378/chest.13-0938. In this study of 226 obese men suspected of having OSA severe hepatic steatosis was independently associated with endothelial dysfunction as measured by plethysmography independent of age, sex, BMI, waist circumference and OSA severity.

    Google Scholar 

  103. Villa E, Camma C, Marietta M, Luongo M, Critelli R, Colopi S, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology. 2012;143(5):1253–60 e1-4. PubMed PMID: 22819864.

    CAS  PubMed  Google Scholar 

  104. Targher G, Bertolini L, Zoppini G, Zenari L, Falezza G. Increased plasma markers of inflammation and endothelial dysfunction and their association with microvascular complications in Type 1 diabetic patients without clinically manifest macroangiopathy. Diabet Med J Br Diabet Assoc. 2005;22(8):999–1004. PubMed PMID: 16026364.

    CAS  Google Scholar 

  105. Hickman IJ, Sullivan CM, Flight S, Campbell C, Crawford DH, Masci PP, et al. Altered clot kinetics in patients with non-alcoholic fatty liver disease. Ann Hepatol. 2009;8((4):331–8. PubMed PMID: 20009132.

    Google Scholar 

  106. Rosito GA, D'Agostino RB, Massaro J, Lipinska I, Mittleman MA, Sutherland P, et al. Association between obesity and a prothrombotic state: the Framingham Offspring Study. Thromb Haemost. 2004;91(4):683–9. PubMed PMID: 15045128.

    CAS  PubMed  Google Scholar 

  107. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss. Arterioscler Thromb Vasc Biol. 2006;26(5):968–76. PubMed PMID: 16627822.

    CAS  PubMed  Google Scholar 

  108. Thogersen AM, Jansson JH, Boman K, Nilsson TK, Weinehall L, Huhtasaari F, et al. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor. Circulation. 1998;98(21):2241–7. PubMed PMID: 9826309.

    CAS  PubMed  Google Scholar 

  109. Verrijken A, Francque S, Mertens I, Prawitt J, Caron S, Hubens G, et al. Prothrombotic factors in histologically proven nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology. 2014;59(1):121–9. In a recent study of obese and overweight patients who underwent metabolic assessment and liver biopsy, the levels of PAI-1 increased significantly with the severity of NASH thereby providing another pathophysiological link between NASH and CVD.

    CAS  PubMed  Google Scholar 

  110. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;482(7384):179–85. Recent study that assessed the role of the inflammasome in NASH by dietary induction of steatohepatitis in inflammasome-deficient mice. Inflammasome-deficiency-associated changes in the configuration of the gut microbiota was associated with increased hepatic steatosis and inflammation. Altered interactions between the gut microbiota and the host, produced by defective inflammasome sensing, may influence the rate of progression of multiple metabolic syndrome-associated abnormalities, including NASH.

  111. Csak T, Ganz M, Pespisa J, Kodys K, Dolganiuc A, Szabo G. Fatty acid and endotoxin activate inflammasomes in mouse hepatocytes that release danger signals to stimulate immune cells. Hepatology. 2011;54(1):133–44. PubMed PMID: 21488066.

    CAS  PubMed  Google Scholar 

  112. Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, 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(8):1091–103. PubMed PMID: 19240062 Pubmed Central PMCID: 2702831.

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Mouzaki M, Comelli EM, Arendt BM, Bonengel J, Fung SK, Fischer SE, et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology. 2013;58(1):120–7. In this study examining the intestinal microbiome (IM) of adults with NASH compared to those with isolated steatosis, differences in the IM between the groups was demonstrated. Specifically, patients with NASH were noted to have gut flora relatively deficient in Bacteriodetes, which typically comprises the majority of the normal human IM.

    CAS  PubMed  Google Scholar 

  114. Zhu L, Baker SS, Gill C, Liu W, Alkhouri R, Baker RD, et al. Hepatology. 2013;57(2):601–9. PubMed PMID: 23055155.

    CAS  PubMed  Google Scholar 

  115. Cope K, Risby T, Diehl AM. Increased gastrointestinal ethanol production in obese mice: implications for fatty liver disease pathogenesis. Gastroenterology. 2000;119(5):1340–7. PubMed PMID: 11054393.

    CAS  PubMed  Google Scholar 

  116. Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R, et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009;49(6):1877–87. PubMed PMID: 19291785.

    CAS  PubMed  Google Scholar 

  117. Farhadi A, Gundlapalli S, Shaikh M, Frantzides C, Harrell L, Kwasny MM, et al. Susceptibility to gut leakiness: a possible mechanism for endotoxaemia in non-alcoholic steatohepatitis. Liver Int Off J Int Assoc Study Liver. 2008;28(7):1026–33. PubMed PMID: 18397235.

    Google Scholar 

  118. Yang SQ, Lin HZ, Lane MD, Clemens M, Diehl AM. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci U S A. 1997;94(6):2557–62. PubMed PMID: 9122234. Pubmed Central PMCID: 20127.

    CAS  PubMed Central  PubMed  Google Scholar 

  119. Backhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A. 2007;104(3):979–84. PubMed PMID: 17210919 Pubmed Central PMCID: 1764762.

    CAS  PubMed Central  PubMed  Google Scholar 

  120. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472(7341):57–63. PubMed PMID: 21475195 Pubmed Central PMCID: 3086762.

    CAS  PubMed Central  PubMed  Google Scholar 

  121. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368(17):1575–84. TMAO (trimethylamine-N-oxide) is a metabolite produced during dietary choline metabolism by intestinal microbiome. TMAO is proatherosclerotic. Patients were fed high choline diet before and after suppression of intestinal microbiota with antibiotics. Fasting TMAO levels and major CVD events were studied during 3 year follow-up in 4007 patients. Antibiotics decreased TMAO levels. High TMAO levels was associated with increased risk of CVD events.

    CAS  PubMed Central  PubMed  Google Scholar 

  122. Goland S, Shimoni S, Zornitzki T, Knobler H, Azoulai O, Lutaty G, et al. Cardiac abnormalities as a new manifestation of nonalcoholic fatty liver disease: echocardiographic and tissue Doppler imaging assessment. J Clin Gastroenterol. 2006;40(10):949–55. PubMed PMID: 17063117.

    PubMed  Google Scholar 

  123. Chinali M, Devereux RB, Howard BV, Roman MJ, Bella JN, Liu JE, et al. Comparison of cardiac structure and function in American Indians with and without the metabolic syndrome (the Strong Heart Study). Am J Cardiol. 2004;93(1):40–4. PubMed PMID: 14697463.

    PubMed  Google Scholar 

  124. Fotbolcu H, Yakar T, Duman D, Karaahmet T, Tigen K, Cevik C, et al. Impairment of the left ventricular systolic and diastolic function in patients with non-alcoholic fatty liver disease. Cardiol J. 2010;17(5):457–63. PubMed PMID: 20865675.

    PubMed  Google Scholar 

  125. Perseghin G, Lattuada G, De Cobelli F, Esposito A, Belloni E, Ntali G, et al. Increased mediastinal fat and impaired left ventricular energy metabolism in young men with newly found fatty liver. Hepatology. 2008;47(1):51–8. PubMed PMID: 17955548.

    CAS  PubMed  Google Scholar 

  126. Pettersen E, Helle-Valle T, Edvardsen T, Lindberg H, Smith HJ, Smevik B, et al. Contraction pattern of the systemic right ventricle shift from longitudinal to circumferential shortening and absent global ventricular torsion. J Am Coll Cardiol. 2007;49(25):2450–6. PubMed PMID: 17599609.

    PubMed  Google Scholar 

  127. Singh GK, Vitola BE, Holland MR, Sekarski T, Patterson BW, Magkos F, et al. Alterations in ventricular structure and function in obese adolescents with nonalcoholic fatty liver disease. J Pediatr. 2013;162(6):1160–8, 8 e1. PubMed PMID: 23260104. Pubmed Central PMCID: 361514.

    PubMed  Google Scholar 

  128. Sert A, Aypar E, Pirgon O, Yilmaz H, Odabas D, Tolu I. Left ventricular function by echocardiography, tissue Doppler imaging, and carotid intima-media thickness in obese adolescents with nonalcoholic fatty liver disease. Am J Cardiol. 2013;112(3):436–43. PubMed PMID: 23642511.

    PubMed  Google Scholar 

  129. Hallsworth K, Hollingsworth KG, Thoma C, Jakovljevic D, MacGowan GA, Anstee QM, et al. Cardiac structure and function are altered in adults with non-alcoholic fatty liver disease. J Hepatol. 2013;58(4):757–62. In a study using high-resolution cardiac MRI, differences in cardiac structure were compared between adults with NAFLD and matched healthy controls without NAFLD or MetS. Patients with NAFLD had increased ventricular thickness in both systole and diastole as well as decreased longitudinal shortening indicating remodeling and sub-endocardial strain.

    PubMed  Google Scholar 

  130. Targher G, Valbusa F, Bonapace S, Bertolini L, Zenari L, Rodella S, et al. Non-alcoholic fatty liver disease is associated with an increased incidence of atrial fibrillation in patients with type 2 diabetes. PloS One. 2013;8(2):e57183. PubMed PMID: 23451184 Pubmed Central PMCID: 3579814.

    CAS  PubMed Central  PubMed  Google Scholar 

  131. Bernardi M, Calandra S, Colantoni A, Trevisani F, Raimondo ML, Sica G, et al. Q-T interval prolongation in cirrhosis: prevalence, relationship with severity, and etiology of the disease and possible pathogenetic factors. Hepatology. 1998;27(1):28–34. PubMed PMID: 9425913.

    CAS  PubMed  Google Scholar 

  132. Bal JS, Thuluvath PJ. Prolongation of QTc interval: relationship with etiology and severity of liver disease, mortality and liver transplantation. Liver Int Off J Int Assoc Study Liver. 2003;23(4):243–8. PubMed PMID: 12895263.

    Google Scholar 

  133. Shin WJ, Kim YK, Song JG, Kim SH, Choi SS, Song JH, et al. Alterations in QT interval in patients undergoing living donor liver transplantation. Transplant Proc. 2011;43(1):170–3. PubMed PMID: 21335179.

    PubMed  Google Scholar 

  134. Pillai AA, Rinella ME. Non-alcoholic fatty liver disease: is bariatric surgery the answer? Clin Liver Dis. 2009;13(4):689–710. PubMed PMID: 19818313.

    PubMed  Google Scholar 

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Acknowledgement

We would like to thank Ms. Christine De Sayve and Dr. Itishree Trivedi for their illustrations used in Fig. 1.

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Itishree Trivedi declares no conflicts of interest.

Mary E. Rinella declares no conflicts of interest.

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  1. Feinberg School of Medicine, Division of Gastroenterology and Hepatology, Northwestern University, 676 N. St. Clair, Arkes Pavilion, 14-005, Chicago, IL, 60611, USA

    Itishree Trivedi & Mary E. Rinella

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Trivedi, I., Rinella, M.E. NAFLD and Cardiovascular Disease: Can the Real Association Be Determined?. Curr Hepatology Rep 13, 130–141 (2014). https://doi.org/10.1007/s11901-014-0231-9

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