Quantification of Liver Fat in NAFLD: Available Modalities and Clinical Significance

Abstract

Purpose of Review

To review the available modalities for quantification of liver fat in nonalcoholic fatty liver disease (NAFLD) and their clinical significance.

Recent Findings

Ultrasonography remains the first line imaging used to diagnose NAFLD as it is widely available and relatively inexpensive. Controlled attenuation parameter can be used as a screening tool for fatty liver as it is reasonably accurate and provides simultaneous estimation of hepatic fibrosis. Magnetic resonance imaging proton density fat fraction and magnetic resonance spectroscopy are the most accurate noninvasive modalities for quantification of hepatic steatosis. Liver biopsy remains the gold standard but is limited by the invasive nature of the procedure, and observer and sampling variability. This may be improved with novel computer-assisted stereological analysis or second harmonic generation microscopy.

Summary

Understanding the advantages and disadvantages of each of the modalities will help one choose the most suitable method for quantifying hepatic steatosis in NAFLD.

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References

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

  1. 1.

    Wah-Kheong C, Khean-Lee G. Epidemiology of a fast emerging disease in the Asia-Pacific region: non-alcoholic fatty liver disease. Hepatol Int. 2013;7:65–71.

    PubMed  Google Scholar 

  2. 2.

    • 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;64:73–84 The meta-analysis reporting on the latest global prevalence and clinical and economic burden of NAFLD.

    PubMed  Google Scholar 

  3. 3.

    Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011;43:617–49.

    PubMed  Google Scholar 

  4. 4.

    Sayiner M, Otgonsuren M, Cable R, Younossi I, Afendy M, Golabi P, et al. Variables associated with inpatient and outpatient resource utilization among Medicare beneficiaries with nonalcoholic fatty liver disease with or without cirrhosis. J Clin Gastroenterol. 2017;51:254–60.

    PubMed  Google Scholar 

  5. 5.

    Wong VW, Chan WK, Chitturi S, Chawla Y, Dan YY, Duseja A, et al. Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-Part 1: definition, risk factors and assessment. J Gastroenterol Hepatol. 2018;33:70–85.

    PubMed  Google Scholar 

  6. 6.

    Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123:745–50.

    PubMed  Google Scholar 

  7. 7.

    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;52:579–85.

    CAS  PubMed  Google Scholar 

  8. 8.

    • Hernaez R, Lazo M, Bonekamp S, Kamel I, Brancati FL, Guallar E, et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology. 2011;54:1082–90 Important major meta-analysis reporting on the reliabilty and accuracy in detecting moderate-to-severe fatty liver, compared with histology.

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Strauss S, Gavish E, Gottlieb P, Katsnelson L. Interobserver and intraobserver variability in the sonographic assessment of fatty liver. AJR Am J Roentgenol. 2007;189:W320–3.

    PubMed  Google Scholar 

  10. 10.

    Lee SS, Park SH. Radiologic evaluation of nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20:7392–402.

    PubMed  PubMed Central  Google Scholar 

  11. 11.

    Kromrey ML, Ittermann T, Berning M, Kolb C, Hoffmann RT, Lerch MM, et al. Accuracy of ultrasonography in the assessment of liver fat compared with MRI. Clin Radiol. 2019;74:539–46.

    CAS  PubMed  Google Scholar 

  12. 12.

    Lee DH. Imaging evaluation of non-alcoholic fatty liver disease: focused on quantification. Clinical and molecular hepatology. 2017;23:290–301.

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    • Webb M, Yeshua H, Zelber-Sagi S, Santo E, Brazowski E, Halpern Z, et al. Diagnostic value of a computerized hepatorenal index for sonographic quantification of liver steatosis. AJR Am J Roentgenol. 2009;192:909–14 The original article describing hepatorenal sonograhic index as a sensitive noninvasive method for steatosis quantification.

    PubMed  Google Scholar 

  14. 14.

    de Almeidae Borges VF, ALD D, Cotrim HP, HLOG R, Andrade NB. Sonographic hepatorenal ratio: a noninvasive method to diagnose nonalcoholic steatosis. J Clin Ultrasound. 2013;41:18–25.

    Google Scholar 

  15. 15.

    Son JY, Lee JY, Yi NJ, Lee KW, Suh KS, Kim KG, et al. Hepatic steatosis: assessment with acoustic structure quantification of US imaging. Radiology. 2016;278:257–64.

    PubMed  Google Scholar 

  16. 16.

    Kuroda H, Kakisaka K, Kamiyama N, Oikawa T, Onodera M, Sawara K, et al. Non-invasive determination of hepatic steatosis by acoustic structure quantification from ultrasound echo amplitude. World J Gastroenterol. 2012;18:3889–95.

    PubMed  PubMed Central  Google Scholar 

  17. 17.

    Lin SC, Heba E, Wolfson T, Ang B, Gamst A, Han A, et al. Noninvasive diagnosis of nonalcoholic fatty liver disease and quantification of liver fat using a new quantitative ultrasound technique. Clin Gastroenterol Hepatol. 2015;13:1337–1345.e1336.

    PubMed  Google Scholar 

  18. 18.

    Pickhardt PJ, Park SH, Hahn L, Lee SG, Bae KT, Yu ES. Specificity of unenhanced CT for non-invasive diagnosis of hepatic steatosis: implications for the investigation of the natural history of incidental steatosis. Eur Radiol. 2012;22:1075–82.

    PubMed  Google Scholar 

  19. 19.

    Birnbaum BA, Hindman N, Lee J, Babb JS. Multi-detector row CT attenuation measurements: assessment of intra- and interscanner variability with an anthropomorphic body CT phantom. Radiology. 2007;242:109–19.

    PubMed  Google Scholar 

  20. 20.

    Park YS, Park SH, Lee SS, Kim DY, Shin YM, Lee W, et al. Biopsy-proven nonsteatotic liver in adults: estimation of reference range for difference in attenuation between the liver and the spleen at nonenhanced CT. Radiology. 2011;258:760–6.

    PubMed  Google Scholar 

  21. 21.

    Zhang Y, Wang C, Duanmu Y, Zhang C, Zhao W, Wang L, et al. Comparison of CT and magnetic resonance mDIXON-Quant sequence in the diagnosis of mild hepatic steatosis. Br J Radiol. 2018;91:20170587.

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    Reeder SB, Cruite I, Hamilton G, Sirlin CB. Quantitative assessment of liver fat with magnetic resonance imaging and spectroscopy. J Magn Reson Imaging. 2011;34:729–49.

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Chartampilas E. Imaging of nonalcoholic fatty liver disease and its clinical utility. Hormones (Athens). 2018;17:69–81.

    Google Scholar 

  24. 24.

    Qu Y, Li M, Hamilton G, Zhang YN, Song B. Diagnostic accuracy of hepatic proton density fat fraction measured by magnetic resonance imaging for the evaluation of liver steatosis with histology as reference standard: a meta-analysis. Eur Radiol 2019.

  25. 25.

    •• Bohte AE, van Werven JR, Bipat S, Stoker J. 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. 2011;21:87–97 The meta-analysis describing diagnostic accuracy of US, CT, MRI, and MRS, compared with histology in evaluating hepatic steatosis.

    PubMed  Google Scholar 

  26. 26.

    Zheng D, Guo Z, Schroder PM, Zheng Z, Lu Y, Gu J, et al. Accuracy of MR imaging and MR spectroscopy for detection and quantification of hepatic steatosis in living liver donors: a meta-analysis. Radiology. 2017;282:92–102.

    PubMed  Google Scholar 

  27. 27.

    Gu J, Liu S, Du S, Zhang Q, Xiao J, Dong Q, et al. Diagnostic value of MRI-PDFF for hepatic steatosis in patients with non-alcoholic fatty liver disease: a meta-analysis. Eur Radiol. 2019;29:3564–73.

    PubMed  Google Scholar 

  28. 28.

    Idilman IS, Keskin O, Celik A, Savas B, Elhan AH, Idilman R, et al. 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. 2016;57:271–8.

    PubMed  Google Scholar 

  29. 29.

    Heba ER, Desai A, Zand KA, Hamilton G, Wolfson T, Schlein AN, et al. Accuracy and the effect of possible subject-based confounders of magnitude-based MRI for estimating hepatic proton density fat fraction in adults, using MR spectroscopy as reference. J Magn Reson Imaging. 2016;43:398–406.

    PubMed  Google Scholar 

  30. 30.

    Yokoo T, Serai SD, Pirasteh A, Bashir MR, Hamilton G, Hernando D, et al. Linearity, bias, and precision of hepatic proton density fat fraction measurements by using MR imaging: a meta-analysis. Radiology. 2018;286:486–98.

    PubMed  Google Scholar 

  31. 31.

    Kang GH, Cruite I, Shiehmorteza M, Wolfson T, Gamst AC, Hamilton G, et al. Reproducibility of MRI-determined proton density fat fraction across two different MR scanner platforms. J Magn Reson Imaging. 2011;34:928–34.

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Bachtiar V, Kelly MD, Wilman HR, Jacobs J, Newbould R, Kelly CJ, et al. Repeatability and reproducibility of multiparametric magnetic resonance imaging of the liver. PLoS One. 2019;14:e0214921.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Adams LA. End-points for drug treatment in NASH. Hepatol Int. 2019;13:253–8.

    PubMed  Google Scholar 

  34. 34.

    Caussy C, Reeder SB, Sirlin CB, Loomba R. Noninvasive, quantitative assessment of liver fat by MRI-PDFF as an endpoint in NASH trials. Hepatology. 2018;68:763–72.

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Siddiqui MS, Harrison SA, Abdelmalek MF, Anstee QM, Bedossa P, Castera L, et al. Case definitions for inclusion and analysis of endpoints in clinical trials for nonalcoholic steatohepatitis through the lens of regulatory science. Hepatology. 2018;67:2001–12.

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Loomba R, Sirlin CB, Ang B, Bettencourt R, Jain R, Salotti J, et al. Ezetimibe for the treatment of nonalcoholic steatohepatitis: assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial). Hepatology. 2015;61:1239–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    •• Noureddin M, Lam J, Peterson MR, Middleton M, Hamilton G, Le TA, et al. Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials. Hepatology. 2013;58:1930–40 The original paper describing MRI-PDFF and MRS correlated well and more sensitive than histology in quantifying steatosis changes.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    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. Ther Adv Gastroenterol. 2016;9:692–701.

    CAS  Google Scholar 

  39. 39.

    Di Martino M, Pacifico L, Bezzi M, Di Miscio R, Sacconi B, Chiesa C, et al. Comparison of magnetic resonance spectroscopy, proton density fat fraction and histological analysis in the quantification of liver steatosis in children and adolescents. World J Gastroenterol. 2016;22:8812–9.

    PubMed  PubMed Central  Google Scholar 

  40. 40.

    • 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;36:1825–35 The original paper describing controlled attenuation parameter for evaluation of hepatic steatosis in patients with chronic liver disease.

    PubMed  Google Scholar 

  41. 41.

    •• Sasso M, Tengher-Barna I, Ziol M, Miette V, Fournier C, Sandrin L, et al. Novel controlled attenuation parameter for noninvasive assessment of steatosis using Fibroscan((R)): validation in chronic hepatitis C. J Viral Hepat. 2012;19:244–53 The original paper providing validation of controlled attenuation parameter for evaluation of hepatic steatosis.

    CAS  PubMed  Google Scholar 

  42. 42.

    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;32:902–10.

    PubMed  Google Scholar 

  43. 43.

    de Ledinghen V, Vergniol J, Foucher J, Merrouche W, le Bail B. Non-invasive diagnosis of liver steatosis using controlled attenuation parameter (CAP) and transient elastography. Liver Int. 2012;32:911–8.

    PubMed  Google Scholar 

  44. 44.

    Kumar M, Rastogi A, Singh T, Behari C, Gupta E, Garg H, et al. Controlled attenuation parameter for non-invasive assessment of hepatic steatosis: does etiology affect performance? J Gastroenterol Hepatol. 2013;28:1194–201.

    PubMed  Google Scholar 

  45. 45.

    Chon YE, Jung KS, Kim SU, Park JY, Park YN, Kim DY, et al. Controlled attenuation parameter (CAP) for detection of hepatic steatosis in patients with chronic liver diseases: a prospective study of a native Korean population. Liver Int. 2014;34:102–9.

    PubMed  Google Scholar 

  46. 46.

    Masaki K, Takaki S, Hyogo H, Kobayashi T, Fukuhara T, Naeshiro N, et al. Utility of controlled attenuation parameter measurement for assessing liver steatosis in Japanese patients with chronic liver diseases. Hepatol Res. 2013;43:1182–9.

    PubMed  Google Scholar 

  47. 47.

    • Chan WK, Nik Mustapha NR, Mahadeva S. Controlled attenuation parameter for the detection and quantification of hepatic steatosis in nonalcoholic fatty liver disease. J Gastroenterol Hepatol. 2014;29:1470–6 The original paper on controlled attenuation parameter for evaluation of hepatic steatosis in NAFLD patients that described reduced accuracy with increased body mass index.

    CAS  PubMed  Google Scholar 

  48. 48.

    • Shen F, Zheng RD, Shi JP, Mi YQ, Chen GF, Hu X, et al. Impact of skin capsular distance on the performance of controlled attenuation parameter in patients with chronic liver disease. Liver Int. 2015;35:2392–400 The original paper on controlled attenuation parameter for evaluation of hepatic steatosis that showed reduced accuracy with increased skin capsular distance.

    PubMed  PubMed Central  Google Scholar 

  49. 49.

    Yilmaz Y, Yesil A, Gerin F, Ergelen R, Akin H, Celikel CA, et al. Detection of hepatic steatosis using the controlled attenuation parameter: a comparative study with liver biopsy. Scand J Gastroenterol. 2014;49:611–6.

    PubMed  Google Scholar 

  50. 50.

    Shen F, Zheng RD, Mi YQ, Wang XY, Pan Q, Chen GY, et al. Controlled attenuation parameter for non-invasive assessment of hepatic steatosis in Chinese patients. World J Gastroenterol. 2014;20:4702–11.

    PubMed  PubMed Central  Google Scholar 

  51. 51.

    Karlas T, Petroff D, Garnov N, Bohm S, Tenckhoff H, Wittekind C, et al. Non-invasive assessment of hepatic steatosis in patients with NAFLD using controlled attenuation parameter and 1H-MR spectroscopy. PLoS One. 2014;9:e91987.

    PubMed  PubMed Central  Google Scholar 

  52. 52.

    de Ledinghen 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;60:1026–31.

    PubMed  Google Scholar 

  53. 53.

    Ferraioli G, Tinelli C, Lissandrin R, Zicchetti M, Dal Bello B, Filice G, et al. Controlled attenuation parameter for evaluating liver steatosis in chronic viral hepatitis. World J Gastroenterol. 2014;20:6626–31.

    PubMed  PubMed Central  Google Scholar 

  54. 54.

    Jung KS, Kim BK, Kim SU, Chon YE, Chun KH, Kim SB, et al. Factors affecting the accuracy of controlled attenuation parameter (CAP) in assessing hepatic steatosis in patients with chronic liver disease. PLoS One. 2014;9:e98689.

    PubMed  PubMed Central  Google Scholar 

  55. 55.

    Wang CY, Lu W, Hu DS, Wang GD, Cheng XJ. Diagnostic value of controlled attenuation parameter for liver steatosis in patients with chronic hepatitis B. World J Gastroenterol. 2014;20:10585–90.

    PubMed  PubMed Central  Google Scholar 

  56. 56.

    Lupsor-Platon M, Feier D, Stefanescu H, Tamas A, Botan E, Sparchez Z, et al. Diagnostic accuracy of controlled attenuation parameter measured by transient elastography for the non-invasive assessment of liver steatosis: a prospective study. J Gastrointestin Liver Dis. 2015;24:35–42.

    PubMed  Google Scholar 

  57. 57.

    Mi YQ, Shi QY, Xu L, Shi RF, Liu YG, Li P, et al. Controlled attenuation parameter for noninvasive assessment of hepatic steatosis using Fibroscan(R): validation in chronic hepatitis B. Dig Dis Sci. 2015;60:243–51.

    CAS  PubMed  Google Scholar 

  58. 58.

    • Chan WK, Nik Mustapha NR, Wong GL, Wong VW, Mahadeva S. Controlled attenuation parameter using the FibroScan(R) XL probe for quantification of hepatic steatosis for non-alcoholic fatty liver disease in an Asian population. United European Gastroenterol J. 2017;5:76–85 The original paper on controlled attenuation parameter using XL probe in NAFLD patients, showing similar accuracy for evaluation of hepatic steatosis as the conventional M probe.

    PubMed  Google Scholar 

  59. 59.

    Cardoso AC, Beaugrand M, de Ledinghen V, Douvin C, Poupon R, Trinchet JC, et al. Diagnostic performance of controlled attenuation parameter for predicting steatosis grade in chronic hepatitis B. Ann Hepatol. 2015;14:826–36.

    CAS  PubMed  Google Scholar 

  60. 60.

    de Ledinghen V, Wong GL, Vergniol J, Chan HL, Hiriart JB, Chan AW, et al. Controlled attenuation parameter for the diagnosis of steatosis in non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2016;31:848–55.

    PubMed  Google Scholar 

  61. 61.

    Chen J, Wu D, Wang M, Chen E, Bai L, Liu C, et al. Controlled attenuation parameter for the detection of hepatic steatosis in patients with chronic hepatitis B. Infect Dis (Lond). 2016;48:670–5.

    CAS  Google Scholar 

  62. 62.

    Hong YM, Yoon KT, Cho M, Chu CW, Rhu JH, Yang KH, et al. Clinical usefulness of controlled attenuation parameter to screen hepatic steatosis for potential donor of living donor liver transplant. Eur J Gastroenterol Hepatol. 2017;29:805–10.

    PubMed  Google Scholar 

  63. 63.

    Wong VW, Petta S, Hiriart JB, Camma C, Wong GL, Marra F, et al. Validity criteria for the diagnosis of fatty liver by M probe-based controlled attenuation parameter. J Hepatol. 2017;67:577–84.

    PubMed  Google Scholar 

  64. 64.

    • de Ledinghen V, Hiriart JB, Vergniol J, Merrouche W, Bedossa P, Paradis V. Controlled attenuation parameter (CAP) with the XL probe of the fibroscan((R)): a comparative study with the M probe and liver biopsy. Dig Dis Sci. 2017;62:2569–77 The original paper on controlled attenuation parameter using XL probe in patients with chronic liver disease of various aetiologies, showing similar accuracy for evaluation of hepatic steatosis as the conventional M probe.

    PubMed  Google Scholar 

  65. 65.

    Andrade P, Rodrigues S, Rodrigues-Pinto E, Gaspar R, Lopes J, Lopes S, et al. Diagnostic accuracy of controlled attenuation parameter for detecting hepatic steatosis in patients with chronic liver disease. GE Port J Gastroenterol. 2017;24:161–8.

    PubMed  Google Scholar 

  66. 66.

    Thiele M, Rausch V, Fluhr G, Kjaergaard M, Piecha F, Mueller J, et al. Controlled attenuation parameter and alcoholic hepatic steatosis: diagnostic accuracy and role of alcohol detoxification. J Hepatol. 2018;68:1025–32.

    CAS  PubMed  Google Scholar 

  67. 67.

    • Chan WK, Nik Mustapha NR, Mahadeva S, Wong VW, Cheng JY, Wong GL. Can the same controlled attenuation parameter cut-offs be used for M and XL probes for diagnosing hepatic steatosis? J Gastroenterol Hepatol. 2018;33:1787–94 The original paper on controlled attenuation parameter using XL probe in patients with chronic liver disease of various aetiologies, suggesting that the same cutoffs may be used as for the conventional M probe for the diagnosis of the different grades of hepatic steatosis.

    PubMed  Google Scholar 

  68. 68.

    Mendes LC, Ferreira PA, Miotto N, Zanaga L, Lazarini MS, Goncales ESL, et al. Controlled attenuation parameter for steatosis grading in chronic hepatitis C compared with digital morphometric analysis of liver biopsy: impact of individual elastography measurement quality. Eur J Gastroenterol Hepatol. 2018;30:959–66.

    PubMed  Google Scholar 

  69. 69.

    Yen YH, Kuo FY, Lin CC, Chen CL, Chang KC, Tsai MC, et al. Predicting hepatic steatosis in living liver donors via controlled attenuation parameter. Transplant Proc. 2018;50:3533–8.

    CAS  PubMed  Google Scholar 

  70. 70.

    Eddowes PJ, Sasso M, Allison M, Tsochatzis E, Anstee QM, Sheridan D, et al. Accuracy of FibroScan controlled attenuation parameter and liver stiffness measurement in assessing steatosis and fibrosis in patients with nonalcoholic fatty liver disease. Gastroenterology. 2019;156:1717–30.

    PubMed  Google Scholar 

  71. 71.

    Rout G, Kedia S, Nayak B, Yadav R, Das P, Acharya SK, et al. Controlled attenuation parameter for assessment of hepatic steatosis in Indian patients. J Clin Exp Hepatol. 2019;9:13–21.

    PubMed  Google Scholar 

  72. 72.

    Baumeler S, Jochum W, Neuweiler J, Bergamin I, Semela D. Controlled attenuation parameter for the assessment of liver steatosis in comparison with liver histology: a single-centre real life experience. Swiss Med Wkly. 2019;149:w20077.

    PubMed  Google Scholar 

  73. 73.

    Somda S, Lebrun A, Tranchart H, Lamouri K, Prevot S, Njike-Nakseu M, et al. Adaptation of controlled attenuation parameter (CAP) measurement depth in morbidly obese patients addressed for bariatric surgery. PLoS One. 2019;14:e0217093.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 74.

    Semmler G, Stift J, Scheiner B, Woran K, Schwabl P, Paternostro R, Bucsics T, et al. Performance of controlled attenuation parameter in patients with advanced chronic liver disease and portal hypertension. Dig Dis Sci 2019.

  75. 75.

    Xu L, Lu W, Li P, Shen F, Mi YQ, Fan JG. A comparison of hepatic steatosis index, controlled attenuation parameter and ultrasound as noninvasive diagnostic tools for steatosis in chronic hepatitis B. Dig Liver Dis. 2017;49:910–7.

    PubMed  Google Scholar 

  76. 76.

    •• Karlas T, Petroff D, Sasso M, Fan JG, Mi YQ, de Ledinghen V, et al. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J Hepatol. 2017;66:1022–30 The individual patient data meta-analysis that defined the optimal cutoffs for the diagnosis of the different grades of hepatic steatosis.

    PubMed  Google Scholar 

  77. 77.

    Myers RP, Pomier-Layrargues G, Kirsch R, Pollett A, Duarte-Rojo A, Wong D, et al. Feasibility and diagnostic performance of the FibroScan XL probe for liver stiffness measurement in overweight and obese patients. Hepatology. 2012;55:199–208.

    PubMed  Google Scholar 

  78. 78.

    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;67:1348–59.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79.

    •• Boursier J, Zarski JP, de Ledinghen V, Rousselet MC, Sturm N, Lebail B, et al. Determination of reliability criteria for liver stiffness evaluation by transient elastography. Hepatology. 2013;57:1182–91 The original article that defined the reliability criteria for transient elastography.

    PubMed  Google Scholar 

  80. 80.

    Ratchatasettakul K, Rattanasiri S, Promson K, Sringam P, Sobhonslidsuk A. The inverse effect of meal intake on controlled attenuation parameter and liver stiffness as assessed by transient elastography. BMC Gastroenterol. 2017;17:50.

    PubMed  PubMed Central  Google Scholar 

  81. 81.

    Silva M, Costa Moreira P, Peixoto A, Santos AL, Lopes S, Goncalves R, et al. Effect of meal ingestion on liver stiffness and controlled attenuation parameter. GE Port J Gastroenterol. 2019;26:99–104.

    PubMed  Google Scholar 

  82. 82.

    Arena U, Lupsor Platon M, Stasi C, Moscarella S, Assarat A, Bedogni G, et al. Liver stiffness is influenced by a standardized meal in patients with chronic hepatitis C virus at different stages of fibrotic evolution. Hepatology. 2013;58:65–72.

    CAS  PubMed  Google Scholar 

  83. 83.

    • Kwak MS, Chung GE, Yang JI, Yim JY, Chung SJ, Jung SY, et al. Clinical implications of controlled attenuation parameter in a health check-up cohort. Liver Int. 2018;38:915–23 The original article evaluating the use of CAP in a health check-up population.

    CAS  PubMed  Google Scholar 

  84. 84.

    Seto WK, Hui RWH, Mak LY, Fung J, Cheung KS, Liu KSH, et al. Association between hepatic steatosis, measured by controlled attenuation parameter, and fibrosis burden in chronic hepatitis B. Clin Gastroenterol Hepatol. 2018;16:575–83 e572.

    PubMed  Google Scholar 

  85. 85.

    • 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;150:626–637 e627 The original article that compared the diagnostic accuracy of MRI-PDFF and CAP for the diagnosis of the different grades of hepatic steatosis in NAFLD patients.

    PubMed  Google Scholar 

  86. 86.

    Runge JH, Smits LP, Verheij J, Depla A, Kuiken SD, Baak BC, et al. MR spectroscopy-derived proton density fat fraction is superior to controlled attenuation parameter for detecting and grading hepatic steatosis. Radiology. 2018;286:547–56.

    PubMed  Google Scholar 

  87. 87.

    Margini C, Murgia G, Stirnimann G, De Gottardi A, Semmo N, Casu S, et al. Prognostic significance of controlled attenuation parameter in patients with compensated advanced chronic liver disease. Hepatol Commun. 2018;2:929–40.

    PubMed  PubMed Central  Google Scholar 

  88. 88.

    Scheiner B, Steininger L, Semmler G, Unger LW, Schwabl P, Bucsics T, et al. Controlled attenuation parameter does not predict hepatic decompensation in patients with advanced chronic liver disease. Liver Int. 2019;39:127–35.

    PubMed  Google Scholar 

  89. 89.

    Liu K, Wong VW, Lau K, Liu SD, Tse YK, Yip TC, et al. Prognostic value of controlled attenuation parameter by transient elastography. Am J Gastroenterol. 2017;112:1812–23.

    PubMed  Google Scholar 

  90. 90.

    • 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;67:328–57 The latest guidelines from the AASLD on diagnosis and management of NAFLD.

    PubMed  Google Scholar 

  91. 91.

    •• Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–21 The original article on the histological scoring system for NAFLD, including the grading of hepatic steatosis, which has been used as the reference standard for most studies on diagnostic tests for hepatic steatosis.

    Google Scholar 

  92. 92.

    Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005;128:1898–906.

    PubMed  Google Scholar 

  93. 93.

    • St Pierre TG, House MJ, Bangma SJ, Pang W, Bathgate A, Gan EK, et al. Stereological analysis of liver biopsy histology sections as a reference standard for validating non-invasive liver fat fraction measurements by MRI. PLoS One. 2016;11:e0160789 The original article describing the use of stereological anlaysis as reference standard for measuring hepatic steatosis.

    PubMed  PubMed Central  Google Scholar 

  94. 94.

    Sun W, Chang S, Tai DC, Tan N, Xiao G, Tang H, et al. Nonlinear optical microscopy: use of second harmonic generation and two-photon microscopy for automated quantitative liver fibrosis studies. J Biomed Opt. 2008;13:064010.

    PubMed  Google Scholar 

  95. 95.

    Xu S, Wang Y, Tai DCS, Wang S, Cheng CL, Peng Q, et al. qFibrosis: a fully-quantitative innovative method incorporating histological features to facilitate accurate fibrosis scoring in animal model and chronic hepatitis B patients. J Hepatol. 2014;61:260–9.

    PubMed  PubMed Central  Google Scholar 

  96. 96.

    • Goh GB, Leow WQ, Liang S, Wan WK, Lim TKH, Tan CK, et al. Quantification of hepatic steatosis in chronic liver disease using novel automated method of second harmonic generation and two-photon excited fluorescence. Sci Rep. 2019;9:2975 The original article describing the use of second harmonic generation microscopy for measurement of hepatic steatosis.

    PubMed  PubMed Central  Google Scholar 

  97. 97.

    Pilichiewicz AN, Feltrin KL, Horowitz M, Holtmann G, Wishart JM, Jones KL, et al. Functional dyspepsia is associated with a greater symptomatic response to fat but not carbohydrate, increased fasting and postprandial CCK, and diminished PYY. Am J Gastroenterol. 2008;103:2613–23.

    CAS  PubMed  Google Scholar 

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Correspondence to Wah-Kheong Chan.

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Kee-Huat Chuah declares no potential conflicts of interest.

Wah-Kheong Chan reports speaking for Echosens and a grant from Resonance Health for an investigator-initiated study.

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

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Chuah, KH., Chan, WK. Quantification of Liver Fat in NAFLD: Available Modalities and Clinical Significance. Curr Hepatology Rep 18, 492–502 (2019). https://doi.org/10.1007/s11901-019-00493-x

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Keywords

  • Hepatic steatosis
  • MRI-PDFF
  • MRS
  • CAP