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Noninvasive imaging biomarker assessment of liver fibrosis by elastography in NAFLD

Nature Reviews Gastroenterology & Hepatology volume 15, pages 274–282 (2018)Cite this article

Subjects

Key Points

  • NAFLD is the most common form of chronic liver disease, and patient-centred risk-assessment strategies are therefore needed for cost-effective care

  • Liver elastography — or liver stiffness measurement — is an alternative to liver biopsy to evaluate patients with NAFLD for the presence of advanced fibrosis or cirrhosis

  • Of the available elastographic modalities, vibration-controlled transient elastography is the most studied and magnetic resonance elastography is the most accurate; ultrasound-based elastography is promising but lacks defined examination quality criteria

  • Future research is needed to establish the optimal sequence of modalities for use in the clinic and the definition of clinically meaningful changes in liver stiffness

Abstract

NAFLD is a global epidemic. The prevalence of NAFLD is 20–30% in North America, northern Europe, Australia, Japan, India and China. It is crucial that patients with NAFLD receive an assessment for their risk of advanced fibrosis, which increases the risk of hepatocellular carcinoma and other complications of cirrhosis. Risk stratification that is efficient, cost-effective, patient-centred and evidence-based is one of the most important issues facing clinicians who care for those with liver disease. Given patients' preference to avoid liver biopsy, noninvasive alternatives to assess liver fibrosis are in high demand. The most accurate noninvasive methods are based on liver elastography. Research on these techniques — which include vibration-controlled transient elastography (VCTE), magnetic resonance elastography (MRE), shear-wave elastography and acoustic radiation force impulse — has proliferated. Unfortunately, the literature has not kept pace with clinical practice. There is limited guidance for how clinicians should anticipate and manage the pitfalls of these tests. Furthermore, guidance is unavailable for clinicians regarding the optimal incorporation of VCTE, MRE or the emerging elastographic techniques into their clinical strategy, particularly for patients with NAFLD. In this Review, we summarize the available evidence, highlight gaps to address in further research and explore optimization of these techniques in clinical practice.

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Figure 1: Example images from elastographic techniques.
Figure 2: A suggested strategy for risk stratification of patients with NAFLD using multiple elastographic methods.

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References

  1. Vernon, G., Baranova, A. & Younossi, Z. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment. Pharmacol. Ther. 34, 274–285 (2011).

    Article  CAS  PubMed  Google Scholar 

  2. Williams, C. D. 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 140, 124–131 (2011).

    Article  PubMed  Google Scholar 

  3. Mozumdar, A. & Liguori, G. Persistent increase of prevalence of metabolic syndrome among US adults: NHANES III to NHANES 1999–2006. Diabetes Care 34, 216–219 (2011).

    Article  PubMed  Google Scholar 

  4. Peery, A. F. et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology 143, 1179–1187.e3 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ekstedt, M. et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology 61, 1547–1554 (2015).

    Article  CAS  PubMed  Google Scholar 

  6. Angulo, P. et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 149, 389–397.e10 (2012).

    Article  Google Scholar 

  7. Pasha, T., Gabriel, S., Therneau, T., Dickson, E. R. & Lindor, K. D. Cost-effectiveness of ultrasound-guided liver biopsy. Hepatology 27, 1220–1226 (1998).

    Article  CAS  PubMed  Google Scholar 

  8. Rockey, D. C., Caldwell, S. H., Goodman, Z. D., Nelson, R. C. & Smith, A. D. Liver biopsy. Hepatology 49, 1017–1044 (2009).

    Article  PubMed  Google Scholar 

  9. Foster, G. et al. Management of chronic hepatitis C: clinical audit of biopsy based management algorithm. BMJ 315, 453–458 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bedossa, P., Dargère, D. & Paradis, V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology 38, 1449–1457 (2003).

    Article  PubMed  Google Scholar 

  11. Bedossa, P. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology 20, 15–20 (1994).

    Article  Google Scholar 

  12. Tapper E. B. & Lok A. S. F. Use of liver imaging and biopsy in clinical practice. N. Engl. J. Med. 377, 756–768 (2017).

    Article  PubMed  Google Scholar 

  13. Dietrich, C. F. et al. EFSUMB Guidelines and Recommendations on the clinical use of liver ultrasound elastography, update 2017 (Long version). Ultraschall Med. 34, 169–184 (2013).

    Article  PubMed  Google Scholar 

  14. Tapper, E. B. et al. Levels of alanine aminotransferase confound use of transient elastography to diagnose fibrosis in patients with chronic hepatitis C virus infection. Clin. Gastroenterol. Hepatol. 10, 932–937.e1 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tapper, E. B., Castera, L. & Afdhal, N. H. FibroScan (vibration-controlled transient elastography): where does it stand in the United States practice. Clin. Gastroenterol. Hepatol. 13, 27–36 (2015).

    Article  PubMed  Google Scholar 

  16. Boursier, J. 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. 65, 570–578 (2016).

    Article  PubMed  Google Scholar 

  17. Castéra, L. et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology 51, 828–835 (2010).

    PubMed  Google Scholar 

  18. Park, C. C. 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 152, 598–607.e2 (2017). This study performs a head to head comparison of VCTE and MRE in a US cohort.

    Article  PubMed  Google Scholar 

  19. Cassinotto, C. et al. Liver stiffness in nonalcoholic fatty liver disease: a comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy. Hepatology 63, 1817–1827 (2016). This is the only study to evaluate VCTE, SWE and ARFI in patients with NAFLD.

    Article  PubMed  Google Scholar 

  20. Tapper, E. B., Challies, T., Nasser, I., Afdhal, N. H. & Lai, M. The performance of vibration controlled transient elastography in a us cohort of patients with nonalcoholic fatty liver disease. Am. J. Gastroenterol. 111, 677–684 (2016). The first report of VCTE use for NAFLD in the US (using the M probe).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wong V. W. et al. Liver stiffness measurement using XL probe in patients with nonalcoholic fatty liver disease. Am. J. Gastroenterol. 107, 1862–1871 (2012).

    Article  PubMed  Google Scholar 

  22. Imajo, K. et al. Magnetic resonance imaging more accurately classifies steatosis and fibrosis in patients with nonalcoholic fatty liver disease than transient elastography. Gastroenterology 150, 626–637.e7 (2016).

    Article  PubMed  Google Scholar 

  23. Chen, J. et al. Diagnostic performance of MR elastography and vibration-controlled transient elastography in the detection of hepatic fibrosis in patients with severe to morbid obesity. Radiology 283, 418–428 (2017).

    Article  PubMed  Google Scholar 

  24. Karlas, T. et al. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. J. Hepatol. 66, 1022–1030 (2017).

    Article  PubMed  Google Scholar 

  25. Caussy, C. et al. Optimal threshold of controlled attenuation parameter with MRI-PDFF as the gold standard for the detection of hepatic steatosis. Hepatology https://doi.org/10.1002/hep.29639 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wong V. W. et al. Validity criteria for the diagnosis of fatty liver by M probe-based controlled attenuation parameter. J. Hepatol. 67, 577–584 (2017).

    Article  PubMed  Google Scholar 

  27. Petta, S. et al. Improved noninvasive prediction of liver fibrosis by liver stiffness measurement in patients with nonalcoholic fatty liver disease accounting for controlled attenuation parameter values. Hepatology 65, 1145–1155 (2017). This study uses CAP during VCTE exams to account for the contribution of steatosis to liver stiffness.

    Article  CAS  PubMed  Google Scholar 

  28. Deffieux, T. et al. Investigating liver stiffness and viscosity for fibrosis, steatosis and activity staging using shear wave elastography. J. Hepatol. 62, 317–324 (2015).

    Article  PubMed  Google Scholar 

  29. Cassinotto, C. et al. Non-invasive assessment of liver fibrosis with impulse elastography: comparison of Supersonic Shear Imaging with ARFI and FibroScan®. J. Hepatol. 61, 550–557 (2014).

    Article  PubMed  Google Scholar 

  30. Friedrich-Rust, M. et al. Liver fibrosis in viral hepatitis: noninvasive assessment with acoustic radiation force impulse imaging versus transient elastography. Radiology 252, 595–604 (2009).

    Article  PubMed  Google Scholar 

  31. Cui, J. et al. Magnetic resonance elastography is superior to acoustic radiation force impulse for the Diagnosis of fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease: a prospective study. Hepatology 63, 453–461 (2016).

    Article  PubMed  Google Scholar 

  32. Palmeri, M. L. et al. Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with nonalcoholic fatty liver disease. J. Hepatol. 55, 666–672 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Ebinuma, H. et al. Evaluation of liver fibrosis by transient elastography using acoustic radiation force impulse: comparison with Fibroscan®. J. Gastroenterol. 46, 1238 (2011).

    Article  PubMed  Google Scholar 

  34. Yoon, K. T. et al. Liver stiffness measurement using acoustic radiation force impulse (ARFI) elastography and effect of necroinflammation. Dig. Dis. Sci. 57, 1682–1691 (2012).

    Article  PubMed  Google Scholar 

  35. Venkatesh, S. K., Yin, M. & Ehman, R. L. Magnetic resonance elastography of liver: technique, analysis, and clinical applications. J. Magnet. Resonance Imag. 37, 544–555 (2013).

    Article  Google Scholar 

  36. Loomba, R. et al. Novel 3D magnetic resonance elastography for the noninvasive diagnosis of advanced fibrosis in NAFLD: a prospective study. Am. J. Gastroenterol. 111, 986–994 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Loomba, R. et al. Magnetic resonance elastography predicts advanced fibrosis in patients with nonalcoholic fatty liver disease: a prospective study. Hepatology 60, 1920–1928 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wagner, M. et al. Technical failure of MR elastography examinations of the liver: experience from a large single-center study. Radiology 284, 401–412 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Cui, J. et al. Comparative diagnostic accuracy of magnetic resonance elastography versus 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. 41, 1271–1280 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Dulai, P. S., Sirlin, C. B. & 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. 65, 1006–1016 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Cui, J. et al. Sitagliptin versus placebo for non-alcoholic fatty liver disease: a randomized controlled trial. J. Hepatol. 65, 369–376 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Loomba, R. 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 61, 1239–1250 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Noureddin, M. et al. Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials. Hepatology 58, 1930–1940 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Le, T. A. et al. Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: a randomized controlled trial. Hepatology 56, 922–932 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Satkunasingham, J. et al. Can negligible hepatic steatosis determined by MRI-proton density fat fraction obviate the need for liver biopsy in potential liver donors? Liver Transpl. https://doi.org/10.1002/lt.24965 (2017).

    Article  PubMed  Google Scholar 

  46. Lin, S. C. et al. Noninvasive diagnosis of nonalcoholic fatty liver disease and quantification of liver fat using a new quantitative ultrasound technique. Clin. Gastroenterol. Hepatol. 13, 1337–1345.e6 (2015).

    Article  PubMed  Google Scholar 

  47. Tapper, E. B., Sengupta, N., Hunink, M. M., Afdhal, N. H. & Lai, M. Cost-effective evaluation of nonalcoholic fatty liver disease with NAFLD fibrosis score and vibration controlled transient elastography. Am. J. Gastroenterol. 110, 1298–1304 (2015).

    Article  PubMed  Google Scholar 

  48. Bruix, J. & Sherman, M. Management of hepatocellular carcinoma: an update. Hepatology 53, 1020–1022 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Garcia-Tsao, G., Abraldes, J. G., Berzigotti, A. & Bosch, J. Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology 65, 310–335 (2017).

    Article  PubMed  Google Scholar 

  50. Sanyal, A. J. et al. Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis: findings and recommendations from an American Association for the Study of Liver Diseases–US Food and Drug Administration Joint Workshop. Hepatology 61, 1392–1405 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Patel, N. S. et al. Weight loss decreases magnetic resonance elastography estimated liver stiffness in nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 15, 463–464 (2017).

    Article  PubMed  Google Scholar 

  52. Tapper, E. B., Hunink, M. M., Afdhal, N. H., Lai, M. & Sengupta, N. Cost-effectiveness analysis: risk stratification of nonalcoholic fatty liver disease (NAFLD) by the Primary Care Physician using the NAFLD fibrosis score. PLOS ONE 11, e0147237 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Chalasani, N. et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 55, 2005–2023 (2012).

    Article  PubMed  Google Scholar 

  54. Petta, S. et al. The severity of steatosis influences liver stiffness measurement in patients with nonalcoholic fatty liver disease. Hepatology 62, 1101–1110 (2015).

    Article  PubMed  Google Scholar 

  55. Kumar, R. et al. Liver stiffness measurements in patients with different stages of nonalcoholic fatty liver disease: diagnostic performance and clinicopathological correlation. Dig. Dis. Sci. 58, 265–274 (2013).

    Article  PubMed  Google Scholar 

  56. Chan, W.-K., Mustapha, N. R. N. & Mahadeva, S. A novel 2-step approach combining the NAFLD fibrosis score and liver stiffness measurement for predicting advanced fibrosis. Hepatol. Int. 9, 594–602 (2015).

    Article  PubMed  Google Scholar 

  57. Aykut, U. E. et al. A comparison of FibroMeter NAFLD Score, NAFLD fibrosis score, and transient elastography as noninvasive diagnostic tools for hepatic fibrosis in patients with biopsy-proven non-alcoholic fatty liver disease. Scand. J. Gastroenterol. 49, 1343–1348 (2014).

    Article  PubMed  Google Scholar 

  58. Naveau, S. et al. The diagnostic accuracy of transient elastography for the diagnosis of liver fibrosis in bariatric surgery candidates with suspected NAFLD. Obes. Surg. 24, 1693–1701 (2014).

    Article  PubMed  Google Scholar 

  59. Gaia, S. et al. Reliability of transient elastography for the detection of fibrosis in non-alcoholic fatty liver disease and chronic viral hepatitis. J. Hepatol. 54, 64–71 (2011).

    Article  PubMed  Google Scholar 

  60. Mahadeva, S. et al. Performance of transient elastography (TE) and factors associated with discordance in non-alcoholic fatty liver disease. J. Digestive Diseases 14, 604–610 (2013).

    Google Scholar 

  61. Wong, V. W. S. et al. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology 51, 454–462 (2010).

    Article  CAS  PubMed  Google Scholar 

  62. Ochi, H. et al. Real-time tissue elastography for evaluation of hepatic fibrosis and portal hypertension in nonalcoholic fatty liver diseases. Hepatology 56, 1271–1278 (2012).

    Article  PubMed  Google Scholar 

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Acknowledgements

R.L. is supported in part by the grant R01-DK106419-03. Research reported in this publication was supported in part by the US National Institute of Environmental Health Sciences of the US National Institutes of Health under award number P42ES010337. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US NIH.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, University of Michigan, MI, USA

    Elliot B. Tapper

  2. Institute for Healthcare Policy and Innovation, University of Michigan, MI, USA

    Elliot B. Tapper

  3. Veterans Affairs Hospital, Ann Arbor, MI, USA

    Elliot B. Tapper

  4. Division of Epidemiology, University of California, San Diego, CA, USA

    Rohit Loomba

  5. Division of Gastroenterology, NAFLD Research Center, University of California, San Diego, CA, USA

    Rohit Loomba

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Both authors contributed equally to this article.

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Correspondence to Rohit Loomba.

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R.L. has received research funding support from General Electric and Siemens.

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Tapper, E., Loomba, R. Noninvasive imaging biomarker assessment of liver fibrosis by elastography in NAFLD. Nat Rev Gastroenterol Hepatol 15, 274–282 (2018). https://doi.org/10.1038/nrgastro.2018.10

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