Hormones

pp 1–13 | Cite as

Imaging of nonalcoholic fatty liver disease and its clinical utility

Review Article

Abstract

The prevalence of nonalcoholic fatty liver disease has been continuously rising over the last three decades and is projected to become the most common indication for liver transplantation in the near future. Its pathophysiology and complex interplay with diabetes and the metabolic syndrome are not as yet fully understood despite growing scientific interest and research. Modern imaging techniques offer significant assistance in this field by enabling the study of the liver noninvasively and evaluation of the degree of both steatosis and fibrosis, and even in attempting to diagnose the presence of inflammation (steatohepatitis). The derived measurements are highly precise, accurate and reproducible, performing better than biopsy in terms of quantification. In this article, these imaging techniques are overviewed and their performance regarding diagnosis, stratification and monitoring are evaluated. Their expanding role both in the research arena and in clinical practice along with their limitations is also discussed.

Keywords

Nonalcoholic fatty liver disease Fat quantification Liver fibrosis Ultrasound CT MRI MR spectroscopy MR elastography 

Notes

Conflicts of Interest

The authors have no conflicts of interests to report.

References

  1. 1.
    Zois CD, Baltayiannis GH, Bekiari A et al (2010) Steatosis and steatohepatitis in postmortem material from Northwestern Greece. World J Gastroenterol 16:3944–3949CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Chalasani N, Younossi Z, Lavine JE et al (2017) The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology 67:328–357CrossRefPubMedGoogle Scholar
  3. 3.
    EASL-EASD-EASO (2016) Clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 64:1388–1402Google Scholar
  4. 4.
    Rinella ME (2015) Nonalcoholic fatty liver disease: a systematic review. JAMA 313:2263–2273CrossRefPubMedGoogle Scholar
  5. 5.
    Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ (1999) Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 116:1413–1419CrossRefPubMedGoogle Scholar
  6. 6.
    Ekstedt M, Hagström H, Nasr P et al (2015) Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 61:1547–1554CrossRefPubMedGoogle Scholar
  7. 7.
    Younossi ZM, Stepanova M, Rafiq N et al (2011) Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver-related mortality. Hepatology 53:1874–1882CrossRefPubMedGoogle Scholar
  8. 8.
    Polyzos SA, Mantzoros CS (2016) Nonalcoholic fatty future disease. Metabolism 65:1007–1016CrossRefPubMedGoogle Scholar
  9. 9.
    Athyros VG, Tziomalos K, Katsiki N, Doumas M, Karagiannis A, Mikhailidis DP (2015) Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease: an update. World J Gastroenterol 21:6820–6834CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Rockey D, Caldwell S, Goodman Z et al (2009) Liver biopsy. Hepatology 49:1017–1044CrossRefPubMedGoogle Scholar
  11. 11.
    Pournik O, Alavian SM, Ghalichi L et al (2014) Inter-observer and intra-observer agreement in pathological evaluation of non-alcoholic fatty liver disease suspected liver biopsies. Hepat Mon 14:e15167CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Gawrieh S, Knoedler DM, Saeian K et al (2011) Effects of interventions on intra- and interobserver agreement on interpretation of nonalcoholic fatty liver disease histology. Ann Diagn Pathol 15:19–24CrossRefPubMedGoogle Scholar
  13. 13.
    Hernaez R, Lazo M, Bonekamp S et al (2011) Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology 54:1082–1090CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Lee SS, Park SH, Kim HJ et al (2010) Non-invasive assessment of hepatic steatosis: prospective comparison of the accuracy of imaging examinations. J Hepatol 52:579–585CrossRefPubMedGoogle Scholar
  15. 15.
    van Werven JR, Marsman HA, Nederveen AJ et al (2010) Assessment of hepatic steatosis in patients undergoing liver resection: comparison of US, CT, T1-weighted dual-echo MR imaging, and point-resolved 1H MR spectroscopy. Radiology 256:159–168CrossRefPubMedGoogle Scholar
  16. 16.
    Ma X, Holalkere NS, Kambadakone RA et al (2009) Imaging-based quantification of hepatic fat: methods and clinical applications. Radiographics 29:1253–1280CrossRefPubMedGoogle Scholar
  17. 17.
    Topal NB, Orcan S, Sığırlı D et al (2015) Effects of fat accumulation in the liver on hemodynamic variables assessed by Doppler ultrasonography. J Clin Ultrasound 43:26–33PubMedGoogle Scholar
  18. 18.
    Uzun H, Yazici B, Erdogmus B et al (2009) Doppler waveforms of the hepatic veins in children with diffuse fatty infiltration of the liver. Eur J Radiol 71:552–556CrossRefPubMedGoogle Scholar
  19. 19.
    Balci A, Karazincir S, Sumbas H et al (2008) Effects of diffuse fatty infiltration of the liver on portal vein flow hemodynamics. J Clin Ultrasound 36:134–140CrossRefPubMedGoogle Scholar
  20. 20.
    Sasso M, Beaugrand M, de Ledinghen V et al (2010) Controlled attenuation parameter (CAP): a novel VCTE™ guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes. Ultrasound Med Biol 36:1825–1835CrossRefPubMedGoogle Scholar
  21. 21.
    Kodama Y, Ng CS, Wu TT et al (2007) Comparison of CT methods for determining the fat content of the liver. Am J Roentgenol 188:1307–1312CrossRefGoogle Scholar
  22. 22.
    Iwasaki M, Takada Y, Hayashi M et al (2004) Noninvasive evaluation of graft steatosis in living donor liver transplantation. Transplantation 78:1501–1505CrossRefPubMedGoogle Scholar
  23. 23.
    Park SH, Kim PN, Kim KW et al (2006) Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment. Radiology 239:105–112CrossRefPubMedGoogle Scholar
  24. 24.
    Zeb I, Li D, Nasir K, Katz R et al (2012) Computed tomography scans in the evaluation of fatty liver disease in a population based study: the multi-ethnic study of atherosclerosis. Acad Radiol 19:811–818CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Johnston RJ, Stamm ER, Lewin JM et al (1998) Diagnosis of fatty infiltration of the liver on contrast enhanced CT: limitations of liver-minus-spleen attenuation difference measurements. Abdom Imaging 23:409–415CrossRefPubMedGoogle Scholar
  26. 26.
    Qayyum A, Chen DM, Breiman RS et al (2009) Evaluation of diffuse liver steatosis by ultrasound, computed tomography, and magnetic resonance imaging: which modality is best? Clin Imaging 33:110–115CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Limanond P, Raman SS, Lassman C et al (2004) Macrovesicular hepatic steatosis in living related liver donors: correlation between CT and histologic findings. Radiology 230:276–280CrossRefPubMedGoogle Scholar
  28. 28.
    Hyodo T, Yada N, Hori M et al (2017) Multimaterial decomposition algorithm for the quantification of liver fat content by using fast-kilovolt-peak switching dual-energy CT: clinical evaluation. Radiology 283:108–118CrossRefPubMedGoogle Scholar
  29. 29.
    Hur BY, Lee JM, Hyunsik W et al (2014) Quantification of the fat fraction in the liver using dual-energy computed tomography and multimaterial decomposition. J Comput Assist Tomogr 38:845–852CrossRefPubMedGoogle Scholar
  30. 30.
    Kramer H, Pickhardt PJ, Kliewer MA et al (2017) Accuracy of liver fat quantification with advanced CT, MRI, and ultrasound techniques: prospective comparison with MR spectroscopy. Am J Roentgenol 208:92–100CrossRefGoogle Scholar
  31. 31.
    Artz NS, Hines CD, Brunner ST et al (2012) Quantification of hepatic steatosis with dual-energy computed tomography: comparison with tissue reference standards and quantitative magnetic resonance imaging in the ob/ob mouse. Investig Radiol 47:603–610CrossRefGoogle Scholar
  32. 32.
    Yoshimitsu K, Kuroda Y, Nakamuta M et al (2008) Noninvasive estimation of hepatic steatosis using plain CT vs. chemical-shift MR imaging: significance for living donors. J Magn Reson Imaging 28:678–684CrossRefPubMedGoogle Scholar
  33. 33.
    Bohte AE, van Werven JR, Bipat S et al (2011) The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis. Eur Radiol 21:87–97CrossRefPubMedGoogle Scholar
  34. 34.
    Wells SA (2014) Quantification of hepatic fat and iron with magnetic resonance imaging. Magn Reson Imaging Clin N Am 22:397–416CrossRefPubMedGoogle Scholar
  35. 35.
    Permutt Z, Le TA, Peterson MR et al (2012) Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease—MRI accurately quantifies hepatic steatosis in NAFLD. Aliment Pharmacol Ther 36:22–29CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Idilman IS, Keskin O, Celik A et al (2016) A comparison of liver fat content as determined by magnetic resonance imaging-proton density fat fraction and MRS versus liver histology in non-alcoholic fatty liver disease. Acta Radiol 57:271–278CrossRefPubMedGoogle Scholar
  37. 37.
    Tang A, Tan J, Sun M et al (2013) Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis. Radiology 267:422–431CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Szczepaniak LS, Nurenberg P, Leonard D et al (2005) Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 288:E462–E468CrossRefPubMedGoogle Scholar
  39. 39.
    Kinner S, Reeder SB, Yokoo T (2016) Quantitative imaging biomarkers of NAFLD. Dig Dis Sci 61:1337–1347CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Kang BK, Yu ES, Lee SS et al (2012) Hepatic fat quantification: a prospective comparison of magnetic resonance spectroscopy and analysis methods for chemical-shift gradient echo magnetic resonance imaging with histologic assessment as the reference standard. Investig Radiol 47:368–375CrossRefGoogle Scholar
  41. 41.
    Wu CH, Ho MC, Jeng YM et al (2014) Quantification of hepatic steatosis: a comparison of the accuracy among multiple magnetic resonance techniques. J Gastroenterol Hepatol 29:807–813CrossRefPubMedGoogle Scholar
  42. 42.
    Kukuk GM, Hittatiya K, Sprinkart AM et al (2015) Comparison between modified Dixon MRI techniques, MR spectroscopic relaxometry, and different histologic quantification methods in the assessment of hepatic steatosis. Eur Radiol 25:2869–2879CrossRefPubMedGoogle Scholar
  43. 43.
    Idilman IS, Aniktar H, Idilman R et al (2013) Hepatic steatosis: quantification by proton density fat fraction with MR imaging versus liver biopsy. Radiology 267:767–775CrossRefPubMedGoogle Scholar
  44. 44.
    Parente DB, Rodrigues RS, Paiva FF et al (2014) Is MR spectroscopy really the best MR-based method for the evaluation of fatty liver in diabetic patients in clinical practice? PLoS One 9:e112574CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Schwimmer JB, Middleton MS, Behling C et al (2015) Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease. Hepatology 61:1887–1895CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Hines CD, Frydrychowicz A, Hamilton G et al (2011) T(1) independent, T(2) (*) corrected chemical shift based fat-water separation with multi-peak fat spectral modeling is an accurate and precise measure of hepatic steatosis. J Magn Reson Imaging 33:873–881CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Kang GH, Cruite I, Shiehmorteza M et al (2011) Reproducibility of MRI-determined proton density fat fraction across two different MR scanner platforms. J Magn Reson Imaging 34:928–934CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Reeder S, Hu H, Sirlin C (2012) Proton density fat-fraction: a standardized MR-based biomarker of tissue fat concentration. J Magn Reson Imaging 36:1011–1014CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Rehm JL, Wolfgram PM, Hernando D et al (2015) Proton density fat-fraction is an accurate biomarker of hepatic steatosis in adolescent girls and young women. Eur Radiol 25:2921–2930CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Lin SC, Heba E, Bettencourt R et al (2017) Assessment of treatment response in non-alcoholic steatohepatitis using advanced magnetic resonance imaging. Aliment Pharmacol Ther 45:844–854CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Noureddin M, Lam J, Peterson MR et al (2013) Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials. Hepatology 58:1930–1940CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Le TA, Chen J, Changchien C et al (2012) Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: a randomized controlled trial. Hepatology 56:922–932CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Reeder SB (2013) Emerging quantitative magnetic resonance imaging biomarkers of hepatic steatosis. Hepatology 58:1877–1880CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Blake L, Duarte RV, Cummins C (2016) Decision analytic model of the diagnostic pathways for patients with suspected non-alcoholic fatty liver disease using non-invasive transient elastography and multiparametric magnetic resonance imaging. BMJ Open 6:e010507CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Nordbeck P, Ertl G, Ritter O (2015) Magnetic resonance imaging safety in pacemaker and implantable cardioverter defibrillator patients: how far have we come? Eur Heart J 36:1505–1511CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Hamaguchi M, Kojima T, Takeda N et al (2005) The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann Intern Med 143:722–728CrossRefPubMedGoogle Scholar
  57. 57.
    Pais R, Charlotte F, Fedchuk L et al (2013) A systematic review of follow-up biopsies reveals disease progression in patients with non-alcoholic fatty liver. J Hepatol 59:550–556CrossRefPubMedGoogle Scholar
  58. 58.
    Yamaguchi K, Yang L, McCall S et al (2007) Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology 45:1366–1374CrossRefPubMedGoogle Scholar
  59. 59.
    Angulo P, Bugianesi E, Bjornsson ES et al (2013) Simple noninvasive systems predict long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 145:782–789.e4CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Dulai PS, Singh S, Patel J et al (2017) Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology 65:1557–1565CrossRefPubMedGoogle Scholar
  61. 61.
    Wree A, Broderick L, Canbay A et al (2013) From NAFLD to NASH to cirrhosis-new insights into disease mechanisms. Nat Rev Gastroenterol Hepatol 10:627–636CrossRefPubMedGoogle Scholar
  62. 62.
    Singh S, Allen AM, Wang Z et al (2015) Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol 13:643–54.e9CrossRefPubMedGoogle Scholar
  63. 63.
    Rustogi R, Horowitz J, Harmath C et al (2012) Accuracy of MR elastography and anatomic MR imaging features in the diagnosis of severe hepatic fibrosis and cirrhosis. J Magn Reson Imaging 35:1356–1364CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Kaswala DH, Lai M, Afdhal NH (2016) Fibrosis assessment in nonalcoholic fatty liver disease (NAFLD) in 2016. Dig Dis Sci 61:1356–1364CrossRefPubMedGoogle Scholar
  65. 65.
    Ganne-Carrié N, Ziol M, de Ledinghen V et al (2006) Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases. Hepatology 44:1511–1517CrossRefPubMedGoogle Scholar
  66. 66.
    Tsochatzis EA, Gurusamy KS, Ntaoula S et al (2011) Elastography for the diagnosis of severity of fibrosis in chronic liver disease: a meta-analysis of diagnostic accuracy. J Hepatol 54:650–659CrossRefPubMedGoogle Scholar
  67. 67.
    Degos F, Perez P, Roche B et al (2010) Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: a multicenter prospective study (the FIBROSTIC study). J Hepatol 53:1013–1021CrossRefPubMedGoogle Scholar
  68. 68.
    Wong VW, Vergniol J, Wong GL et al (2012) Liver stiffness measurement using XL probe in patients with nonalcoholic fatty liver disease. Am J Gastroenterol 107:1862–1871CrossRefPubMedGoogle Scholar
  69. 69.
    Imajo K, Kessoku T, Honda Y et al (2016) Magnetic resonance imaging more accurately classifies steatosis and fibrosis in patients with nonalcoholic fatty liver disease than transient elastography. Gastroenterology 150:626–637.e7CrossRefPubMedGoogle Scholar
  70. 70.
    Cassinotto C, Boursier J, de Lédinghen V et al (2016) Liver stiffness in nonalcoholic fatty liver disease: a comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy. Hepatology 63:1817–1827CrossRefPubMedGoogle Scholar
  71. 71.
    Venkatesh SK, Yin M, Ehman RL (2013) Magnetic resonance elastography of liver: technique, analysis, and clinical applications. J Magn Reson Imaging 37:544–555CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Runge JH, Bohte AE, Verheij J et al (2014) Comparison of interobserver agreement of magnetic resonance elastography with histopathological staging of liver fibrosis. Abdom Imaging 39:283–290CrossRefPubMedGoogle Scholar
  73. 73.
    Horowitz JM, Venkatesh SK, Ehman RL et al (2017) Evaluation of hepatic fibrosis: a review from the society of abdominal radiology disease focus panel. Abdom Radiol 42:2037–2053CrossRefGoogle Scholar
  74. 74.
    Chen J, Talwalkar JA, Yin M et al (2011) Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography. Radiology 259:749–756CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Tana C, Tana M, Rossi S et al (2016) Hepatic artery resistive index (HARI) and non-alcoholic fatty liver disease (NAFLD) fibrosis score in NAFLD patients: cut-off suggestive of non-alcoholic steatohepatitis (NASH) evolution. J Ultrasound 19:183–189CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Ridolfi F, Abbattista T, Marini F et al (2007) Contrast-enhanced ultrasound to evaluate the severity of chronic hepatitis C. Dig Liver Dis 39:929–935CrossRefPubMedGoogle Scholar
  77. 77.
    Ronot M, Asselah T, Paradis V et al (2010) Liver fibrosis in chronic hepatitis C virus infection: differentiating minimal from intermediate fibrosis with perfusion CT. Radiology 256:135–142CrossRefPubMedGoogle Scholar
  78. 78.
    Wang L, Fan J, Ding X et al (2015) Assessment of liver fibrosis in the early stages with perfusion CT. Int J Clin Exp Med 8:15276–15282PubMedPubMedCentralGoogle Scholar
  79. 79.
    Bandula S, Punwani S, Rosenberg WM et al (2015) Equilibrium contrast-enhanced CT imaging to evaluate hepatic fibrosis: initial validation by comparison with histopathologic sampling. Radiology 275:136–143CrossRefPubMedGoogle Scholar
  80. 80.
    Guo SL, Su LN, Zhai YN et al (2017) The clinical value of hepatic extracellular volume fraction using routine multiphasic contrast-enhanced liver CT for staging liver fibrosis. Clin Radiol 72:242–246CrossRefPubMedGoogle Scholar
  81. 81.
    Dyvorne HA, Jajamovich GH, Bane O et al (2016) Prospective comparison of magnetic resonance imaging to transient elastography and serum markers for liver fibrosis detection. Liver Int 36:659–666CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Wu Z, Matsui O, Kitao A et al (2013) Usefulness of Gd-EOB-DTPA-enhanced MR imaging in the evaluation of simple steatosis and nonalcoholic steatohepatitis. J Magn Reson Imaging 37:1137–1143CrossRefPubMedGoogle Scholar
  83. 83.
    Bastati N, Feier D, Wibmer A et al (2014) Noninvasive differentiation of simple steatosis and steatohepatitis by using gadoxetic acid-enhanced MR imaging in patients with nonalcoholic fatty liver disease: a proof-of-concept study. Radiology 271:739–747CrossRefPubMedGoogle Scholar
  84. 84.
    Smits LP, Coolen BF, Panno MD et al (2016) Noninvasive differentiation between hepatic steatosis and steatohepatitis with MR imaging enhanced with USPIOs in patients with nonalcoholic fatty liver disease: a proof-of-concept study. Radiology 278:782–791CrossRefPubMedGoogle Scholar
  85. 85.
    Pulli B, Wojtkiewicz G, Iwamoto Y et al (2017) Molecular MR imaging of myeloperoxidase distinguishes steatosis from steatohepatitis in nonalcoholic fatty liver disease. Radiology 284:390–400CrossRefPubMedGoogle Scholar
  86. 86.
    Abrigo JM, Shen J, Wong VW et al (2014) Non-alcoholic fatty liver disease: spectral patterns observed from an in vivo phosphorus magnetic resonance spectroscopy study. J Hepatol 60:809–815CrossRefPubMedGoogle Scholar
  87. 87.
    Zhang X, Gao X, Liu BJ et al (2015) Effective staging of fibrosis by the selected texture features of liver: which one is better, CT or MR imaging? Comput Med Imaging Graph 46(Pt 2):227–236CrossRefPubMedGoogle Scholar
  88. 88.
    Daginawala N, Li B, Buch K et al (2016) Using texture analyses of contrast enhanced CT to assess hepatic fibrosis. Eur J Radiol 85:511–517CrossRefPubMedGoogle Scholar
  89. 89.
    Chalasani N, Wilson L, Kleiner DE et al (2008) Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease. J Hepatol 48:829–834CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Carter-Kent C, Brunt EM, Yerian LM et al (2011) Relations of steatosis type, grade, and zonality to histological features in pediatric nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 52:190–197CrossRefPubMedGoogle Scholar
  91. 91.
    Lonardo A, Ballestri S, Marchesini G et al (2015) Nonalcoholic fatty liver disease: a precursor of the metabolic syndrome. Dig Liver Dis 47:181–190CrossRefPubMedGoogle Scholar
  92. 92.
    Targher G, Marchesini G, Byrne CD (2016) Risk of type 2 diabetes in patients with non-alcoholic fatty liver disease: causal association or epiphenomenon? Diabetes Metab 42:142–156CrossRefPubMedGoogle Scholar
  93. 93.
    Sanyal AJ, Abdelmalek MF, Suzuki A et al (2014) No significant effects of ethyl-eicosapentanoic acid on histologic features of nonalcoholic steatohepatitis in a phase 2 trial. Gastroenterology 147:377–84.e1CrossRefPubMedGoogle Scholar
  94. 94.
    Loomba R, Sirlin CB, Ang B et al (2015) Ezetimibe for the treatment of nonalcoholic steatohepatitis: assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial). Hepatology 61:1239–1250CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Patel J, Bettencourt R, Cui J et al (2016) Association of noninvasive quantitative decline in liver fat content on MRI with histologic response in nonalcoholic steatohepatitis. Therap Adv Gastroenterol 9:692–701CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Patel NS, Doycheva I, Peterson MR et al (2015) Effect of weight loss on magnetic resonance imaging estimation of liver fat and volume in patients with nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol 13:561–568CrossRefPubMedGoogle Scholar
  97. 97.
    Doycheva I, Cui J, Nguyen P et al (2016) Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE. Aliment Pharmacol Ther 43:83–95CrossRefPubMedGoogle Scholar
  98. 98.
    Pavlides M, Banerjee R, Tunnicliffe EM et al (2017) Multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease severity. Liver Int 37:1065–1073CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2018

Authors and Affiliations

  1. 1.Bioclinic Private HospitalThessalonikiGreece

Personalised recommendations