The Role of Radiologic Modalities in Diagnosing Nonalcoholic Steatohepatitis (NASH) and Fibrosis

Abstract

Purpose of Review

The dramatic increase in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) fostered the development and evaluation of non-invasive, imaging based methods for diagnosing NAFLD, NASH, and its complications. We herein review different radiologic modalities in diagnosing steatosis, fibrosis, and liver cirrhosis.

Recent Findings

While routine abdominal ultrasound with hyperechogenic liver structure only detects moderate to severe steatosis, controlled attenuation parameter (CAP), magnetic resonance spectroscopy (MRS), and, especially, MRI-proton density fat fraction (MRI-PDFF) are more sensitive to diagnose and quantify steatosis. MRI-PDFF appears suitable to monitor treatment-related changes in liver fat in clinical trials. Liver fibrosis is related to hepatic and extrahepatic morbidity and mortality in NAFLD. Fibrosis and cirrhosis can be suspected by ultrasound-based elastography techniques (vibration-controlled transient elastography, VCTE; acoustic resonance forced impulse imaging, ARFI; shear wave elastography, SWE), which may be used to screen for fibrosis in high-risk patients. MR elastography (MRE) appears advantageous to quantify and stage fibrosis, while angiographic hepatic venous pressure gradient (HVPG) measurement can confirm portal hypertension in cirrhosis. Screening for hepatocellular carcinoma (HCC) in cirrhotic livers is done by ultrasound; suspicious nodules are followed by multiphasic CT/MRI, contrast-enhanced ultrasound (CEUS), or contrast-enhanced MRI.

Summary

Different radiologic modalities exist to screen, diagnose, stage, and monitor steatosis, steatohepatitis, fibrosis, and HCC, thereby complementing liver biopsy and blood biomarkers in the management of patients with NAFLD.

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References

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

  1. 1.

    Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73–84. https://doi.org/10.1002/hep.28431.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Parikh ND, Marrero WJ, Wang J, Steuer J, Tapper EB, Konerman M, et al. Projected increase in obesity and non-alcoholic-steatohepatitis-related liver transplantation waitlist additions in the United States. Hepatology. 2017 Aug 17. https://doi.org/10.1002/hep.29473.

  3. 3.

    Estes C, Anstee QM, Arias-Loste MT, Bantel H, Bellentani S, Caballeria J, Colombo M, Craxi A, Crespo J, Day CP, Geier A, Kondili LA, Lazarus JV, Loomba R, Manns MP, Marchesini G, Negro F, Petta S, Ratziu V, Romero-Gomez M, Sanyal A, Schattenberg JM, Tacke F, Trautwein C, Wei L, Zeuzem S, Razavi H. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030. J Hepatol. 2018;69(4):896–904. https://doi.org/10.1016/j.jhep.2018.05.036

  4. 4.

    • Dulai PS, Singh S, Patel J, Soni M, Prokop LJ, Younossi Z, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology. 2017;65(5):1557–65. https://doi.org/10.1002/hep.29085 This meta-analysis established the link between fibrosis and mortality in NAFLD.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    •• European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388–402. https://doi.org/10.1016/j.jhep.2015.11.004 This is the first international, multidisciplinary guideline on the management of NAFLD.

    Article  Google Scholar 

  6. 6.

    Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328–57. https://doi.org/10.1002/hep.29367.

    Article  PubMed  Google Scholar 

  7. 7.

    • Younossi ZM, Loomba R, Anstee QM, Rinella ME, Bugianesi E, Marchesini G, Neuschwander-Tetri BA, Serfaty L, Negro F, Caldwell SH, Ratziu V, Corey KE, Friedman SL, Abdelmalek MF, Harrison SA, Sanyal AJ, Lavine JE, Mathurin P, Charlton MR, Goodman ZD, Chalasani NP, Kowdley KV, George J, Lindor K. Diagnostic modalities for non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and associated fibrosis. Hepatology. 2018;68(1):349–60. https://doi.org/10.1002/hep.29721. https://doi.org/10.1002/hep.29721. An important and recent review article on diagnostic modalities in NAFLD.

  8. 8.

    Myers RP, Fong A, Shaheen AA. Utilization rates, complications and costs of percutaneous liver biopsy: a population-based study including 4275 biopsies. Liver Int. 2008;28(5):705–12. https://doi.org/10.1111/j.1478-3231.2008.01691.x.

    Article  PubMed  Google Scholar 

  9. 9.

    Loomba R. Role of imaging-based biomarkers in NAFLD: recent advances in clinical application and future research directions. J Hepatol. 2018;68(2):296–304. https://doi.org/10.1016/j.jhep.2017.11.028.

    Article  PubMed  Google Scholar 

  10. 10.

    Baues M, Dasgupta A, Ehling J, Prakash J, Boor P, Tacke F, et al. Fibrosis imaging: current concepts and future directions. Adv Drug Deliv Rev. 2017;121:9–26. https://doi.org/10.1016/j.addr.2017.10.013.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Azhari H. Ultrasound: medical imaging and beyond (an invited review). Curr Pharm Biotechnol. 2012;13(11):2104–16. https://doi.org/10.2174/138920112802502033.

    Article  PubMed  Google Scholar 

  12. 12.

    Seo J, Kim Y-S. Ultrasound imaging and beyond: recent advances in medical ultrasound. Biom Eng Lett. 2017;7:57–8. https://doi.org/10.1007/s13534-017-0030-7.

    Article  Google Scholar 

  13. 13.

    Mozaffari MH, Lee WS. Freehand 3-D ultrasound imaging: a systematic review. Ultrasound Med Biol. 2017;43(10):2099–124. https://doi.org/10.1016/j.ultrasmedbio.2017.06.009.

    Article  PubMed  Google Scholar 

  14. 14.

    Miller DL, Smith NB, Bailey MR, Czarnota GJ, Hynynen K, Makin IR. Bioeffects Committee of the American Institute of Ultrasound in Medicine Overview of therapeutic ultrasound applications and safety considerations. J Ultrasound Med. 2012;31(4):623–34. https://doi.org/10.7863/jum.2012.31.4.623.

    Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Taylor KJ, Gorelick FS, Rosenfield AT, Riely CA. Ultrasonography of alcoholic liver disease with histological correlation. Radiology. 1981;141(1):157–61. https://doi.org/10.1148/radiology.141.1.6270725.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Lee SS, Park SH, Kim HJ, Kim SY, Kim MY, Kim DY, et al. Non-invasive assessment of hepatic steatosis: prospective comparison of the accuracy of imaging examinations. J Hepatol. 2010;52(4):579–85. https://doi.org/10.1016/j.jhep.2010.01.008.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    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. https://doi.org/10.1053/j.gastro.2010.09.038.

    Article  PubMed  Google Scholar 

  18. 18.

    Mishra P, Younossi ZM. Abdominal ultrasound for diagnosis of nonalcoholic fatty liver disease (NAFLD). Am J Gastroenterol. 2007;102(12):2716–7. https://doi.org/10.1111/j.1572-0241.2007.01520.x.

    Article  PubMed  Google Scholar 

  19. 19.

    Lee JY, Kim KM, Lee SG, Yu E, Lim YS, Lee HC, et al. Prevalence and risk factors of non-alcoholic fatty liver disease in potential living liver donors in Korea: a review of 589 consecutive liver biopsies in a single center. J Hepatol. 2007;47(2):239–44. https://doi.org/10.1016/j.jhep.2007.02.007.

    Article  PubMed  Google Scholar 

  20. 20.

    Baumeister SE, Völzke 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. https://doi.org/10.1053/j.gastro.2007.10.024.

    Article  PubMed  Google Scholar 

  21. 21.

    Khov N, Sharma A, Riley TR. Bedside ultrasound in the diagnosis of nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(22):6821–5. https://doi.org/10.3748/wjg.v20.i22.6821.

    Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Battaglia V, Cervelli R. Liver investigations: updating on US technique and contrast-enhanced ultrasound (CEUS). Eur J Radiol. 2017;96:65–73. https://doi.org/10.1016/j.ejrad.2017.08.029.

    Article  PubMed  Google Scholar 

  23. 23.

    Perez NE, Siddiqui FA, Mutchnick MG, Dhar R, Tobi M, Ullah N, et al. Ultrasound diagnosis of fatty liver in patients with chronic liver disease: a retrospective observational study. J Clin Gastroenterol. 2007;41(6):624–9. https://doi.org/10.1097/01.mcg.0000225680.45088.01.

    Article  PubMed  Google Scholar 

  24. 24.

    Dulai PS, Sirlin CB, Loomba R. MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: clinical trials to clinical practice. J Hepatol. 2016;65(5):1006–16. https://doi.org/10.1016/j.jhep.2016.06.005.

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Sasso M, Beaugrand M, de Ledinghen V, Douvin C, Marcellin P, Poupon R, et al. 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. 2010;36(11):1825–35. https://doi.org/10.1016/j.ultrasmedbio.2010.07.005.

    Article  PubMed  Google Scholar 

  26. 26.

    Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F, et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol. 2003;29(12):1705–13. https://doi.org/10.1016/j.ultrasmedbio.2003.07.001.

    Article  PubMed  Google Scholar 

  27. 27.

    Reddy JK, Rao MS. Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am J Physiol Gastrointest Liver Physiol. 2006;290(5):G852–8. https://doi.org/10.1152/ajpgi.00521.2005.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Mikolasevic I, Orlic L, Franjic N, Hauser G, Stimac D, Milic S. Transient elastography (FibroScan®) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - where do we stand? World J Gastroenterol. 2016;22(32):7236–51. https://doi.org/10.3748/wjg.v22.i32.7236.

    Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    • Karlas T, Petroff D, Sasso M, Fan JG, Mi YQ, de Lédinghen V, et al. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol. 2017;66(5):1022–30. https://doi.org/10.1016/j.jhep.2016.12.022 This individual patient data-based meta-analysis identified important confounders for CAP measurement.

    Article  PubMed  Google Scholar 

  30. 30.

    Desai NK, Harney S, Raza R, Al-Ibraheemi A, Shillingford N, Mitchell PD, et al. Comparison of controlled attenuation parameter and liver biopsy to assess hepatic steatosis in pediatric patients. J Pediatr. 2016;173:160–164.e1. https://doi.org/10.1016/j.jpeds.2016.03.021.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    de Lédinghen V, Vergniol J, Capdepont M, Chermak F, Hiriart JB, Cassinotto C, et al. Controlled attenuation parameter (CAP) for the diagnosis of steatosis: a prospective study of 5323 examinations. J Hepatol. 2014;60(5):1026–31. https://doi.org/10.1016/j.jhep.2013.12.018.

    Article  PubMed  Google Scholar 

  32. 32.

    Caussy C, Reeder SB, Sirlin CB, Loomba R. Non-invasive, quantitative assessment of liver fat by MRI-PDFF as an endpoint in NASH trials. Hepatology. 2018 Jan 21;68:763–72. https://doi.org/10.1002/hep.29797.

    Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Kjærgaard M, Thiele M, Jansen C, Stæhr Madsen B, Görtzen J, Strassburg C, et al. High risk of misinterpreting liver and spleen stiffness using 2D shear-wave and transient elastography after a moderate or high calorie meal. PLoS One. 2017;12(4):e0173992. https://doi.org/10.1371/journal.pone.0173992.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Plewes DB, Kucharczyk W. Physics of MRI: a primer. J Magn Reson Imaging. 2012;35(5):1038–54. https://doi.org/10.1002/jmri.23642.

    Article  PubMed  Google Scholar 

  35. 35.

    Handbook of MRI technique, 4th edition. Ed.: C. Westbrook, John Wiley & Sons, 2014. ISBN: 978–1–118-66162-8.

  36. 36.

    Kim KH, Do WJ, Park SH. Improving resolution of MR images with an adversarial network incorporating images with different contrast. Med Phys. 2018;45:3120–31. https://doi.org/10.1002/mp.12945.

    Article  PubMed  Google Scholar 

  37. 37.

    Ibrahim MA, Dublin AB. Magnetic Resonance Imaging (MRI), Gadolinium. 2018 Jan 25. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK482487/

  38. 38.

    Pasquini L, Napolitano A, Visconti E, Longo D, Romano A, Tomà P, et al. Adolinium-based contrast agent-related toxicities. CNS Drugs. 2018;32(3):229–40. https://doi.org/10.1007/s40263-018-0500-1.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Rogowska J, Olkowska E, Ratajczyk W, Wolska L. Gadolinium as a new emerging contaminant of aquatic environments. Environ Toxicol Chem. 2018;37(6):1523–34. https://doi.org/10.1002/etc.4116.

    CAS  Article  PubMed  Google Scholar 

  40. 40.

    Caussy C, Alquiraish MH, Nguyen P, Hernandez C, Cepin S, Fortney LE, et al. Optimal threshold of controlled attenuation parameter with MRI-PDFF as the gold standard for the detection of hepatic steatosis. Hepatology. 2018;67(4):1348–59. https://doi.org/10.1002/hep.29639.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Kim KY, Song JS, Kannengiesser S, Han YM. Hepatic fat quantification using the proton density fat fraction (PDFF): utility of free-drawn-PDFF with a large coverage area. Radiol Med. 2015;120(12):1083–93. https://doi.org/10.1007/s11547-015-0545-x.

    Article  PubMed  Google Scholar 

  42. 42.

    Kim M, Kang BK, Jun DW. Comparison of conventional sonographic signs and magnetic resonance imaging proton density fat fraction for assessment of hepatic steatosis. Sci Rep. 2018;8(1):7759. https://doi.org/10.1038/s41598-018-26019-x.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Wilman HR, Kelly M, Garratt S, Matthews PM, Milanesi M, Herlihy A, et al. Characterisation of liver fat in the UK biobank cohort. PLoS One. 2017;12(2):e0172921. https://doi.org/10.1371/journal.pone.0172921.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    • Middleton MS, Heba ER, Hooker CA, Bashir MR, Fowler KJ, Sandrasegaran K, et al. Agreement between magnetic resonance imaging proton density fat fraction measurements and pathologist-assigned steatosis grades of liver biopsies from adults with nonalcoholic steatohepatitis. Gastroenterology. 2017;153(3):753–61. https://doi.org/10.1053/j.gastro.2017.06.005 This study demonstrated agreement between MRI-PDFF and histological steatosis.

    Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Myers RP, Pollett A, Kirsch R, Pomier-Layrargues G, Beaton M, Levstik M, et al. Controlled attenuation parameter (CAP): a noninvasive method for the detection of hepatic steatosis based on transient elastography. Liver Int. 2012;32(6):902–10. https://doi.org/10.1111/j.1478-3231.2012.02781.x.

    Article  PubMed  Google Scholar 

  46. 46.

    Weiskirchen R, Weiskirchen S, Tacke F. Organ and tissue fibrosis: molecular signals, cellular mechanisms and translational implications. Mol Aspects Med. 2018. https://doi.org/10.1016/j.mam.2018.06.003

  47. 47.

    Sandrin L, Tanter M, Gennisson JL, Catheline S, Fink M. Shear elasticity probe for soft tissues with 1-D transient elastography. IEEE Trans Ultrason Ferroelectr Freq Control. 2002;49(4):436–46. https://doi.org/10.1109/58.996561.

    Article  PubMed  Google Scholar 

  48. 48.

    Sandrin L, Tanter M, Catheline S, Fink M. Shear modulus imaging with 2-D transient elastography. IEEE Trans Ultrason Ferroelectr Freq Control. 2002;49(4):426–35. https://doi.org/10.1109/58.996560.

    Article  PubMed  Google Scholar 

  49. 49.

    Afdhal NH. Fibroscan (transient elastography) for the measurement of liver fibrosis. Gastroenterol Hepatol (N Y). 2012;8(9):605–7.

    Google Scholar 

  50. 50.

    • Boursier J, Vergniol J, Guillet A, Hiriart JB, Lannes A, Le Bail B, et al. Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease. J Hepatol. 2016;65(3):570–8. https://doi.org/10.1016/j.jhep.2016.04.023 This work compared cross-sectional and longitudinal assessments of several serum biomarker tests and elastography in a large cohort of NAFLD patients.

    Article  PubMed  Google Scholar 

  51. 51.

    U.S. Food & Drug Administration (FDA): Echosens’s FibroScan® System. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf12/k123806.pdf. last downloaded: September 17, 2018.

  52. 52.

    Poynard T, Munteanu M, Luckina E, Perazzo H, Ngo Y, Royer L, et al. Liver fibrosis evaluation using real-time shear wave elastography: applicability and diagnostic performance using methods without a gold standard. J Hepatol. 2013;58(5):928–35. https://doi.org/10.1016/j.jhep.2012.12.021.

    Article  PubMed  Google Scholar 

  53. 53.

    Jaffer OS, Lung PF, Bosanac D, Patel VM, Ryan SM, Heneghan MA, et al. Acoustic radiation force impulse quantification: repeatability of measurements in selected liver segments and influence of age, body mass index and liver capsule-to-box distance. Br J Radiol. 2012;85(1018):e858–63. https://doi.org/10.1259/bjr/74797353.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Palmeri ML, Wang MH, Dahl JJ, Frinkley KD, Nightingale KR. Quantifying hepatic shear modulus in vivo using acoustic radiation force. Ultrasound Med Biol. 2008;34:546–58. https://doi.org/10.1016/j.ultrasmedbio.2007.10.009.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Palmeri ML, Wang MH, Rouze NC, Abdelmalek MF, Guy CD, Moser B, et al. Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with nonalcoholic fatty liver disease. J Hepatol. 2011;55(3):666–72. https://doi.org/10.1016/j.jhep.2010.12.019.

    Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Karlas T, Dietrich A, Peter V, Wittekind C, Lichtinghagen R, Garnov N, et al. Evaluation of transient Elastography, acoustic radiation force impulse imaging (ARFI), and enhanced liver function (ELF) score for detection of fibrosis in morbidly obese patients. PLoS One. 2015;10(11):e0141649. https://doi.org/10.1371/journal.pone.0141649.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Friedrich-Rust M, Romen D, Vermehren J, Kriener S, Sadet D, Herrmann E, et al. Acoustic radiation force impulse-imaging and transient elastography for non-invasive assessment of liver fibrosis and steatosis in NAFLD. Eur J Radiol. 2012;81(3):e325–31. https://doi.org/10.1016/j.ejrad.2011.10.029.

    Article  PubMed  Google Scholar 

  58. 58.

    Orlacchio A, Bolacchi F, Antonicoli M, Coco I, Costanzo E, Tosti D, et al. Liver elasticity in NASH patients evaluated with real-time elastography (RTE). Ultrasound Med Biol. 2012;38(4):537–44. https://doi.org/10.1016/j.ultrasmedbio.2011.12.023.

    Article  PubMed  Google Scholar 

  59. 59.

    Chen Y, Luo Y, Huang W, Hu D, Zheng RQ, Cong SZ, et al. Machine-learning-based classification of real-time tissue elastography for hepatic fibrosis in patients with chronic hepatitis B. Comput Biol Med. 2017;89:18–23. https://doi.org/10.1016/j.compbiomed.2017.07.012.

    Article  PubMed  Google Scholar 

  60. 60.

    Bercoff J, Tanter M, Fink M. Supersonic shear imaging: a new technique for soft tissue elasticity mapping. IEEE Trans Ultrason Ferroelectr Freq Control. 2004;51(4):396–409. https://doi.org/10.1109/TUFFC.2004.1295425.

    Article  PubMed  Google Scholar 

  61. 61.

    Deng H, Qi X, Zhang T, Qi X, Yoshida EM, Guo X. Supersonic shear imaging for the diagnosis of liver fibrosis and portal hypertension in liver diseases: a meta-analysis. Expert Rev Gastroenterol Hepatol. 2018;12(1):91–8. https://doi.org/10.1080/17474124.2018.1412257.

    CAS  Article  PubMed  Google Scholar 

  62. 62.

    Herrmann E, de Lédinghen V, Cassinotto C, Chu WC, Leung VY, Ferraioli G, et al. Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography: an individual patient data-based meta-analysis. Hepatology. 2018;67(1):260–72. https://doi.org/10.1002/hep.29179.

    CAS  Article  PubMed  Google Scholar 

  63. 63.

    Mariappan YK, Glaser KJ, Ehman RL. Magnetic resonance elastography: a review. Clin Anat. 2010;23(5):497–511. https://doi.org/10.1002/ca.21006.

    Article  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Cui J, Ang B, Haufe W, Hernandez C, Verna EC, Sirlin CB, et al. Comparative diagnostic accuracy of magnetic resonance elastography vs. eight clinical prediction rules for non-invasive diagnosis of advanced fibrosis in biopsy-proven non-alcoholic fatty liver disease: a prospective study. Aliment Pharmacol Ther. 2015;41(12):1271–80. https://doi.org/10.1111/apt.13196.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  65. 65.

    • Park CC, Nguyen P, Hernandez C, Bettencourt R, Ramirez K, Fortney L, et al. Magnetic resonance elastography vs transient elastography in detection of fibrosis and noninvasive measurement of steatosis in patients with biopsy-proven nonalcoholic fatty liver disease. Gastroenterology. 2017;152(3):598–607.e2. https://doi.org/10.1053/j.gastro.2016.10.026 This work directly compared MRE and VCTE, demonstrating superior performance of MRE for fibrosis staging.

    Article  PubMed  Google Scholar 

  66. 66.

    Hsu C, Caussy C, Imajo K, Chen J, Singh S, Kaulback K, Le MD, Hooker J, Tu X, Bettencourt R, Yin M, Sirlin CB, Ehman RL, Nakajima A, Loomba R. Magnetic resonance vs transient elastography analysis of patients with non-alcoholic fatty liver disease: a systematic review and pooled analysis of individual participants. Clin Gastroenterol Hepatol. 2018. https://doi.org/10.1016/j.cgh.2018.05.059.

  67. 67.

    Xanthakos SA, Podberesky DJ, Serai SD, Miles L, King EC, Balistreri WF, et al. Use of magnetic resonance elastography to assess hepatic fibrosis in children with chronic liver disease. J Pediatr. 2014;164(1):186–8. https://doi.org/10.1016/j.jpeds.2013.07.050.

    Article  PubMed  Google Scholar 

  68. 68.

    Costa-Silva L, Ferolla SM, Lima AS, Vidigal PVT, Ferrari TCA. MR elastography is effective for the non-invasive evaluation of fibrosis and necroinflammatory activity in patients with nonalcoholic fatty liver disease. Eur J Radiol. 2018;98:82–9. https://doi.org/10.1016/j.ejrad.2017.11.003.

    Article  PubMed  Google Scholar 

  69. 69.

    Pavlides M, Banerjee R, Tunnicliffe EM, Kelly C, Collier J, Wang LM, et al. Multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease severity. Liver Int. 2017;37(7):1065–73. doi. https://doi.org/10.1111/liv.13284.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  70. 70.

    Farrar CT, Gale EM, Kennan R, Ramsay I, Masia R, Arora G, et al. CM-101: type I collagen-targeted MR imaging probe for detection of liver fibrosis. Radiology. 2018;287(2):581–9. doi. https://doi.org/10.1148/radiol.2017170595.

    Article  PubMed  Google Scholar 

  71. 71.

    Ehling J, Bartneck M, Fech V, Butzbach B, Cesati R, Botnar R, et al. Elastin-based molecular MRI of liver fibrosis. Hepatology. 2013;58(4):1517–8. doi. https://doi.org/10.1002/hep.26326.

    Article  PubMed  Google Scholar 

  72. 72.

    Cheung JS, Fan SJ, Gao DS, Chow AM, Man K, Wu EX. Diffusion tensor imaging of liver fibrosis in an experimental model. J Magn Reson Imaging. 2010;32(5):1141–8. https://doi.org/10.1002/jmri.22367.

    Article  PubMed  Google Scholar 

  73. 73.

    Li X, Liang Q, Zhuang L, Zhang X, Chen T, Li L, et al. Preliminary study of MR diffusion tensor imaging of the liver for the diagnosis of hepatocellular carcinoma. PLoS One. 2015;10(8):e0135568. https://doi.org/10.1371/journal.pone.0135568.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  74. 74.

    Wong OL, Leung TWT, Lo GG, Yuan J, Li WW, Noseworthy MD. Intrasession and intersession repeatability of diffusion tensor imaging in healthy human liver. J Comput Assist Tomogr. 2017;41(4):578–85. https://doi.org/10.1097/RCT.0000000000000572.

    Article  PubMed  Google Scholar 

  75. 75.

    Ajmera V, Loomba R. Can elastography differentiate isolated fatty liver from nonalcoholic steatohepatitis? Semin Liver Dis. 2018;38(1):14–20. https://doi.org/10.1055/s-0037-1618587.

    Article  PubMed  Google Scholar 

  76. 76.

    Castéra L, Foucher J, Bernard PH, Carvalho F, Allaix D, Merrouche W, et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology. 2010;51(3):828–35. https://doi.org/10.1002/hep.23425 NA.

    Article  PubMed  Google Scholar 

  77. 77.

    Lv S, Jiang S, Liu S, Dong Q, Xin Y, Xuan S. Noninvasive quantitative detection methods of liver fat content in nonalcoholic fatty liver disease. J Clin Transl Hepatol. 2018;6(2):217–21. https://doi.org/10.14218/JCTH.2018.00021.

    Article  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Praveenraj P, Gomes RM, Basuraju S, Kumar S, Senthilnathan P, Parathasarathi R, et al. Preliminary evaluation of acoustic radiation force impulse shear wave imaging to detect hepatic fibrosis in morbidly obese patients before bariatric surgery. J Laparoendosc Adv Surg Tech A. 2016;26(3):192–5. https://doi.org/10.1089/lap.2015.0396.

    Article  PubMed  Google Scholar 

  79. 79.

    Bota S, Sporea I, Sirli R, Popescu A, Danila M, Costachescu D. Intra- and interoperator reproducibility of acoustic radiation force impulse (ARFI) elastography--preliminary results. Ultrasound Med Biol. 2012;38(7):1103–8. https://doi.org/10.1016/j.ultrasmedbio.2012.02.032.

    Article  PubMed  Google Scholar 

  80. 80.

    Liu H, Fu J, Hong R, Liu L, Li F. Acoustic radiation force impulse elastography for the non-invasive evaluation of hepatic fibrosis in non-alcoholic fatty liver disease patients: a systematic review & meta-analysis. PLoS One. 2015;10(7):e0127782. https://doi.org/10.1371/journal.pone.0127782.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  81. 81.

    Shiraishi A, Hiraoka A, Aibiki T, Okudaira T, Kawamura T, Imai Y, et al. Real-time tissue elastography: non-invasive evaluation of liver fibrosis in chronic liver disease due to HCV. Hepato-Gastroenterology. 2014;61(135):2084–90.

    PubMed  Google Scholar 

  82. 82.

    Choong CC, Venkatesh SK, Siew EP. Accuracy of routine clinical ultrasound for staging of liver fibrosis. J Clin Imaging Sci. 2012;2:58. https://doi.org/10.4103/2156-7514.101000.

    Article  PubMed  PubMed Central  Google Scholar 

  83. 83.

    Kennedy P, Wagner M, Castéra L, Hong CW, Johnson CL, Sirlin CB, et al. Quantitative elastography methods in liver disease: current evidence and future directions. Radiology. 2018;286(3):738–63. https://doi.org/10.1148/radiol.2018170601.

    Article  PubMed  PubMed Central  Google Scholar 

  84. 84.

    de Franchis R, Baveno VI, Faculty. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63(3):743–52. https://doi.org/10.1016/j.jhep.2015.05.022.

    Article  PubMed  Google Scholar 

  85. 85.

    European Association for the Study of the Liver. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406–60. https://doi.org/10.1016/j.jhep.2018.03.024.

    Article  Google Scholar 

  86. 86.

    European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182–236. https://doi.org/10.1016/j.jhep.2018.03.019.

    Article  Google Scholar 

  87. 87.

    Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67(1):358–80. https://doi.org/10.1016/j.jhep.2018.03.019.

    Article  PubMed  Google Scholar 

  88. 88.

    Singal A, Volk ML, Waljee A, Salgia R, Higgins P, Rogers MA, et al. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther. 2009;30(1):37–47. https://doi.org/10.1111/j.1365-2036.2009.04014.x.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  89. 89.

    • Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301–14. https://doi.org/10.1016/S0140-6736(18)30010-2 An important recent review on diagnosis and management of liver cancer.

    Article  PubMed  Google Scholar 

  90. 90.

    Di Martino M, De Filippis G, De Santis A, Geiger D, Del Monte M, Lombardo CV, et al. Hepatocellular carcinoma in cirrhotic patients: prospective comparison of US, CT and MR imaging. Eur Radiol. 2013;23(4):887–96. https://doi.org/10.1007/s00330-012-2691-z.

    Article  PubMed  Google Scholar 

  91. 91.

    Renzulli M, Biselli M, Brocchi S, Granito A, Vasuri F, Tovoli F, et al. New hallmark of hepatocellular carcinoma, early hepatocellular carcinoma and high-grade dysplastic nodules on Gd-EOB-DTPA MRI in patients with cirrhosis: a new diagnostic algorithm. Gut. 2018;67:1674–82. https://doi.org/10.1136/gutjnl-2017-315384.

    CAS  Article  PubMed  Google Scholar 

  92. 92.

    • Imajo K, Kessoku T, Honda Y, Tomeno W, Ogawa Y, Mawatari H, et al. Magnetic resonance imaging more accurately classifies steatosis and fibrosis in patients with nonalcoholic fatty liver disease than transient elastography. Gastroenterology. 2016;150(3):626–37. https://doi.org/10.1053/j.gastro.2015.11.048 This work directly compared transient elastography- and MRI-based methods for steatosis and fibrosis assessment in biopsy-confirmed NAFLD patients.

    Article  PubMed  Google Scholar 

  93. 93.

    Patel J, Bettencourt R, Cui J, Salotti J, Hooker J, Bhatt A, et al. Association of noninvasive quantitative decline in liver fat content on MRI with histologic response in nonalcoholic steatohepatitis. Therap Adv Gastroenterol. 2016;9(5):692–701. https://doi.org/10.1177/1756283X16656735.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors sincerely thank Sabine Weiskirchen for preparing the figure for this review article.

Funding

The laboratories of the authors are supported by the German Research Foundation (DFG, SFB/TRR57) and grants from the Interdisciplinary Centre for Clinical Research (projects O3-1, O3-2) within the Faculty of Medicine at the RWTH Aachen University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Correspondence to Ralf Weiskirchen or Frank Tacke.

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Conflict of Interest

Frank Tacke has been supported by funding from Tobira Therapeutics, Bristol Myers Squibb, Galapagos, and Allergan.

Ralf Weiskirchen cooperates with Silence Therapeutics.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Fatty Liver Disease

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Weiskirchen, R., Tacke, F. The Role of Radiologic Modalities in Diagnosing Nonalcoholic Steatohepatitis (NASH) and Fibrosis. Curr Hepatology Rep 17, 324–335 (2018). https://doi.org/10.1007/s11901-018-0421-y

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Keywords

  • Steatosis
  • NAFLD
  • Imaging
  • Radiology
  • Fibroscan
  • MRI
  • Fibrosis